Shandong Cancer Hospital Research Articles

Clinical study on conversion therapy of hepatocellular carcinoma - summary and comparison of clinical data from a single center of consecutive four years

AimThe purpose of this study was to interpret real-world clinical data to analyze the surgical safety and survival outcomes of patients with initial unresectable hepatocellular carcinoma (uHCC) after conversion therapy.MethodsA retrospective analysis was performed on 2984 hepatocellular carcinoma (HCC) patients hospitalized in Shandong Cancer Hospital Affiliated to Shandong First Medical University from June 1st, 2019 to June 1st, 2023. Clinicopathological features, response to systemic and/or loco-regional treatments, surgical resection rate after conversion therapy, surgical safety, and postoperative recurrence were analyzed.ResultsA total of 38 patients were successfully converted to obtain surgical resection. 35 patients underwent radical resection. A high objective response rate (ORR) (52.6% under RECIST v1.1 and 78.9% under mRECIST criteria) was observed in patients under conversion therapy, and the disease control rate (DCR) was 100%. Pathologic complete response (pCR) was 42.9%. Treatment-related adverse events (TRAEs) of any grade were observed in 37 patients (97.4%). Safety of conversion or direct surgery continues to improve. The median follow-up time was 19.3 months. The 1-year Disease-free survival (DFS) rate of patients with direct surgery and patients with conversion surgery were 91.4% and 86.8%, respectively.ConclusionsWith conversion therapy, a small percentage (1.81%) of uHCC patients are likely to be converted to radical resection. Local combined systemic therapy is a relatively safe and effective conversion therapy, and the safety of surgery is gradually improved after successful conversion. Preliminary follow-up data showed satisfactory survival benefits for patients undergoing conversion surgery.Trial registrationThis was a retrospective study and it did not interfere with treatment decisions.

Sintilimab combined with anlotinib and chemotherapy as second-line or later therapy in extensive-stage small cell lung cancer: a phase II clinical trial

Treatment options for patients with relapsed extensive-stage small cell lung cancer (ES-SCLC) remain scarce. This study aims to evaluate the efficacy and safety of combining anlotinib and sintilimab plus chemotherapy as a second line or later therapy for ES-SCLC patients. This is a phase II clinical trial (ChiCTR2100049390) conducting at Shandong Cancer Hospital. Patients with ES-SCLC and received at least one prior systemic treatment were enrolled. The trial design involved a combination therapy (sintilimab, anlotinib, and nab-paclitaxel) administered over six 21-day cycles, followed by maintenance sintilimab therapy. The primary endpoint was objective response rate (ORR). Circulating tumor DNA sequencing was employed for exploratory analysis. From July 2021 to April 2023, 25 eligible patients were enrolled. The confirmed ORR was 60% (95% CI: 38.7–78.9%) and the DCR was 76% (95% CI: 54.9–90.6%). The mPFS was 6.0 months (95% CI: 5.4–9.7), and the 6-month PFS rate was 49.2%. The mOS was 13.4 months (95% CI: 11.8-NR), with a 12-month survival rate of 62.2%. Treatment-related adverse events (TRAEs) of any grade occurred in 80% of patients, with the most common being fatigue (40%) and nausea (32%). TRAEs of Grade 3 or higher were reported in 12% of patients. ctDNA analysis indicated that low on-treatment blood tumor mutation burden was associated with longer PFS and OS and a potential role of KMT2D mutation in treatment resistance. This combination therapy shows promising efficacy and a manageable safety profile as a second-line or later treatment for ES-SCLC, with genomic insights providing potential biomarkers for treatment response.

Prognostic nomogram combining 18F-FDG PET/CT radiomics and clinical data for stage III NSCLC survival prediction

The aim of this study was to establish and validate the precision of a novel radiomics approach that integrates 18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) scan data with clinical information to improve the prognostication of survival rates in patients diagnosed with stage III Non-Small Cell Lung Cancer (NSCLC) who are not candidates for surgery. We evaluated pretreatment 18F-FDG PET-CT scans from 156 individuals diagnosed with stage III inoperable NSCLC at Shandong Cancer Hospital. These individuals were divided into two groups: a training set comprising 110 patients and an internal validation set consisting of 46 patients. By employing random forest classifier and cox proportional hazards model , we identified and utilized relevant features to create predictive models and a nomogram. The effectiveness of these models was assessed through the use of the receiver operating characteristics(ROC) curves, Kaplan–Meier (KM) curves, and the application of the nomogram. Our findings showed that the combined model, which integrates both clinical and radiomic data, outperformed those based solely on clinical or radiomic features in predicting 3-year overall survival(OS). Furthermore, calibration plots revealed a high level of agreement between predicted and actual survival times. The research successfully established a predictive radiomics model that integrates 18F-FDG PET/CT imaging with clinical indicators to enhance survival predictions for patients with stage III inoperable NSCLC.

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.

The relationship between the expression of fibroblast growth factor 19 and insulin-like growth factor 1 in colorectal polyp tissues and the occurrence of colorectal adenomas

Objective: This investigation sought to delineate the associations among colorectal adenomatous polyps, diabetes, and biomolecules involved in glucose metabolism. Method: Data were collected from 40 patients who underwent endoscopic polypectomy at the Endoscopy Department of Shandong Cancer Hospital between June 2019 and September 2021. This cohort included 27 patients with inflammatory polyps and 13 with adenomatous polyps. We assessed fasting insulin (Fins), fasting blood glucose (FBG), and the mRNA expressions of fibroblast growth factor 19 (FGF-19) and insulin-like growth factor 1 (IGF-1) in the polyp tissues. Both univariate and multivariate logistic regression analyses were employed to ascertain the determinants influencing the emergence of adenomatous polyps. From these analyses, a predictive nomogram was constructed to forecast the occurrence of adenomatous polyps, and evaluations on the discriminative capacity, calibration, and clinical utility of the model were conducted. Results: The adenomatous polyp group exhibited markedly elevated levels of glucose, insulin, FGF-19, and IGF-1, with respective concentrations of (8.67±2.70) mmol/L, (12.72±7.69) μU/L, 2.20±1.88, and 1.36±0.69. These figures were significantly higher compared to the inflammatory polyp group, which showed levels of (5.51±0.72) mmol/L, (5.49±2.68) μU/L, 0.53±0.97, and 0.41±0.46, respectively, P=0.001. Multivariate logistic regression revealed that the relative expression of IGF-1 served as an independent risk factor for the development of colorectal adenomatous polyps (OR=5.622, 95% CI:1.085-29.126). The nomogram displayed a C-index of 0.849, indicating substantial discriminative capability. The calibration curve affirmed the model's accuracy in aligning predicted probabilities with actual outcomes, and the clinical decision curve demonstrated thepractical clinical applicability of the model. Conclusions: There was a significant correlation between the occurrence of colorectal adenomatous polyps and glucose metabolic pathways. Individuals with diabetes showed a higher propensity to develop such polyps.

Adebrelimab plus chemotherapy and sequential thoracic radiotherapy as first-line therapy for extensive-stage small–cell lung cancer (ES-SCLC): a phase II trial

This phase II prospective trial aimed to investigate the efficacy and safety of adebrelimab (PD-L1 antibody) plus first-line chemotherapy followed by sequential thoracic radiotherapy (TRT) combined with adebrelimab in extensive-stage small-cell lung cancer (ES-SCLC). Biomarkers associated with potential therapeutic effects were also explored. Patients with previously untreated ES-SCLC were enrolled at Shandong Cancer Hospital and Institute (Jinan, China). Patients received 4-6 cycles of adebrelimab (20mg/kg, D1, Q3W) combined with EP/EC (etoposide, 100mg/m2, D1-3, Q3W and cisplatin, 75mg/m2, D1, Q3W or carboplatin, AUC=5, D1, Q3W). Then patients with response sequentially underwent consolidative TRT (≥30Gy in 10 fractions or≥50Gy in 25 fractions, involved-field irradiation), and maintenance adebrelimab until disease progression or intolerable adverse events (AEs). The primary endpoint was overall survival (OS). Genomic and circulating tumour DNA (ctDNA) profiling were also analyzed with tumour tissues and peripheral blood. This trial was registered with ClinicalTrials.gov, NCT04562337. From October 2020 to April 2023, 67 patients diagnosed with ES-SCLC were enrolled and received at least one dose of study treatment. All patients were included in the efficacy and safety analyses. 45 patients received sequential TRT as planned. The median OS and progression-free survival (PFS) was 21.4 months (95% CI: 17.2-not reached months) and 10.1 months (95% CI: 6.9-15.5 months), respectively. The confirmed objective response rate was 71.6% (48/67, 95% CI: 59.3-82.0%) and disease control rate was 89.6% (60/67, 95% CI: 79.7-95.7%). There were no treatment-related deaths. The most common grade 3 or higher treatment-related adverse events (TRAEs) were hematological toxicities. The incidence of any grade and G3+ pneumonitis was 25% (17/67) and 6% (4/67), respectively. No unexpected adverse events were observed. Patients without co-mutations of TP53/RB1 in both tissue and peripheral blood displayed longer PFS (tissue, P=0.071; ctDNA, P=0.060) and OS (tissue, P=0.032; ctDNA, P=0.031). Adebrelimab plus chemotherapy and sequential TRT as first-line therapy for ES-SCLC showed promising efficacy and acceptable safety. This study was funded by the National Natural Science Foundation of China (82172865), Jiangsu Hengrui Pharmaceuticals Co., Ltd. and Amoy Diagnostics Co., Ltd.

Impact of microwave ablation on survival rates and recurrence in hepatic malignant tumors.

This study aimed to evaluate the efficacy of percutaneous microwave ablation (MWA) for treating hepatic malignant tumors and to identify factors influencing tumor recurrence post-treatment. A total of 249 patients with hepatic malignant tumors treated at the Shandong Cancer Hospital and Institute were included, and 101 patients were analyzed. Disease-free and overall survival rates were assessed at 1, 2, and 3years post-MWA. Correlations between tumor recurrence and factors such as Child-Pugh B classification and lesion count were examined, and a meta-analysis was conducted to identify independent risk factors for recurrence. The study found disease-free survival rates of 80.2%, 72.3%, and 70.3% at 1, 2, and 3years post-MWA, with overall survival rates at 99%, 97%, and 96%. Significant correlations were observed between tumor recurrence, Child-Pugh B classification, and the number of lesions. Meta-analysis confirmed lesion count and Child-Pugh B classification as independent risk factors for recurrence following MWA treatment. The study underscores the importance of considering Child-Pugh B classification and lesion count in predicting tumor recurrence after MWA for hepatic malignant tumors. These findings offer valuable insights for clinicians in decision-making and post-treatment monitoring.

Programmed cell death ligand 1 (PD-L1) inhibitors versus programmed cell death 1 (PD-1) inhibitors for the first-line therapy of extensive-stage small cell lung cancer: A propensity score-matched study.

206 Background: Addition of programmed cell death ligand 1 (PD-L1) inhibitors or programmed cell death 1 (PD-1) inhibitors to etoposide‐platinum (EP) chemotherapy has become the standard first-line regimen for ES-SCLC. The clinical efficacy and safety between the two types of immune checkpoint inhibitors (ICIs) remain controversial. We conduct the retrospective study and propensity score-matched analysis to explore the potential differences between them. Methods: Patients diagnosed with ES-SCLC and treated by EP plus PD-L1 or PD-1 inhibitors at Shandong Cancer Hospital between March 2019 and November 2022 were reviewed retrospectively. According to PD-L1 or PD-1 inhibitors, they were divided into two groups. Propensity score matching (1:1) was performed to balance the baseline characteristics of the two groups. The baseline characteristics and adverse events between the two groups were compared using the chi-squared test. The survival curves of overall survival (OS) and progression-free survival (PFS) were plotted by the Kaplan-Meier method and differences were analyzed by the log-rank test.The primary endpoints were OS and PFS. Results: As a result, 448 patients were analyzed in this study. 264 patients received PD-L1 inhibitors plus EP and 184 received PD-1 inhibitors plus EP. The median follow-up was 17.6 months. The median OS and PFS was 20.4 months and 7.8 months in the overall population. Before propensity score matching, the median OS was 20.1 months in PD-L1 inhibitor plus EP group and 20.7 months in PD-1 inhibitor plus EP group, respectively (HR 1.043, 95%CI 0.776-1.401; p= 0.781). The median PFS was 7.6 months in the PD-L1 inhibitor plus EP group and 8.5 months in PD-1 inhibitor plus EP group (HR 1.099, 95%CI 0.886-1.364; p= 0.390). After propensity score matching, the median OS and PFS were 20.4 months and 7.8months in PD-L1 inhibitor plus EP group, and those were 20.1 months and 8.6 months in PD-1 inhibitor plus EP group. There was no significant difference in OS and PFS between PD-L1 inhibitors plus EP and PD-1 inhibitors plus EP in the matched population (HR 1.104; p= 0.578 and HR 1.072; p= 0.602, respectively). The overall adverse events were comparable in the two groups. Only ≥3 grade neutropenia was more frequent in the PD-L1 inhibitors plus EP group (77.7% vs 69.0%, p= 0.040). Conclusions: In conclusion, the overall efficacy and safety profile was similar between PD-L1 inhibitors and PD-1 inhibitors for the first-line treatment of ES-SCLC.

ViTR-SP: A CT-based vision transformer model for prediction of pneumonitis in patients with non-small cell lung cancer who received thoracic radiotherapy and immunotherapy.

e20034 Background: The combination of thoracic radiotherapy (TRT) and immunotherapy accompanied by the accumulation of pulmonary toxicity. This study aimed to construct a deep radiomics model based on sequential computed tomography (CT) images for radioimmune-associated pneumonitis prediction in non-small cell lung cancer (NSCLC) patients treated with TRT and immune checkpoint inhibitors (ICIs). Methods: Three models were constructed based on a vision transformer (ViT) network using sequential chest CT images, tumor-mask and lung-mask as inputs, respectively. NSCLC patients treated with TRT and ICIs at Shandong Cancer Hospital and Qilu Hospital were included for model training and external validation, respectively. The image-level model was trained based on ViT to identify predictive images, and the image-level probability distribution were performed. Then, a ViT-Recursive Neural Network (ViT-RNN) model framework was constructed at the patient-level to integrate the image-level information to derive the final prediction, which was evaluated in an independent validation cohort. Results: A total of 230 NSCLC patients from Shandong Cancer Hospital were randomly assigned in a 7:3 ratio for model training and validation, respectively. Another 42 patients from Qilu Hospital were used as an independent external validation cohort. The ViT-RNN model for symptomatic pneumonitis (ViTR-SP) based on sequential CT images achieved better area under curve (AUC), sensitivity, and specificity of 0.725, 0.750, and 0.886 than lung-mask based model (0.575, 0.625, and 0.705) and tumor-mask based model (0.658, 0.667, and 0.773) in the internal validation set. In the external validation set, the proposed model achieved the AUC, sensitivity, and specificity of 0.654, 0.818, 0.727, while the lung-mask and tumor-mask based models had the AUC, sensitivity, and specificity of 0.540, 0.545, 0.677, and 0.630, 0.545, 0.742, respectively. The performance of the model was improved after integrating clinical features, with internal and external validation AUC of 0.782 and 0.672, respectively. Conclusions: In conclusion, the clinical combined ViTR-SP neural network risk prediction model based on sequential chest CT images can be used for predicting the risk of developing radioimmune-associated pneumonitis in NSCLC patients.

Programmed cell death ligand 1 (PD-L1) inhibitors versus programmed cell death 1 (PD-1) inhibitors for the first-line therapy of extensive-stage small cell lung cancer: A propensity score-matched study.

8086 Background: Addition of programmed cell death ligand 1 (PD-L1) inhibitors or programmed cell death 1 (PD-1) inhibitors to etoposide‐platinum (EP) chemotherapy has become the standard first-line regimen for ES-SCLC. The clinical efficacy and safety between the two types of immune checkpoint inhibitors (ICIs) remain controversial. We conduct the retrospective study and propensity score-matched analysis to explore the potential differences between them. Methods: Patients diagnosed with ES-SCLC and treated by EP plus PD-L1 or PD-1 inhibitors at Shandong Cancer Hospital between March 2019 and November 2022 were reviewed retrospectively. According to PD-L1 or PD-1 inhibitors, they were divided into two groups. Propensity score matching (1:1) was performed to balance the baseline characteristics of the two groups. The baseline characteristics and adverse events between the two groups were compared using the chi-squared test. The survival curves of overall survival (OS) and progression-free survival (PFS) were plotted by the Kaplan-Meier method and differences were analyzed by the log-rank test.The primary endpoints were OS and PFS. Results: As a result, 448 patients were analyzed in this study. 264 patients received PD-L1 inhibitors plus EP and 184 received PD-1 inhibitors plus EP. The median follow-up was 17.6 months. The median OS and PFS was 20.4 months and 7.8 months in the overall population. Before propensity score matching, the median OS was 20.1 months in PD-L1 inhibitor plus EP group and 20.7 months in PD-1 inhibitor plus EP group, respectively (HR 1.043, 95%CI 0.776-1.401; p= 0.781). The median PFS was 7.6 months in the PD-L1 inhibitor plus EP group and 8.5 months in PD-1 inhibitor plus EP group (HR 1.099, 95%CI 0.886-1.364; p= 0.390). After propensity score matching, the median OS and PFS were 20.4 months and 7.8months in PD-L1 inhibitor plus EP group, and those were 20.1 months and 8.6 months in PD-1 inhibitor plus EP group. There was no significant difference in OS and PFS between PD-L1 inhibitors plus EP and PD-1 inhibitors plus EP in the matched population (HR 1.104; p= 0.578 and HR 1.072; p= 0.602, respectively). The overall adverse events were comparable in the two groups. Only ≥3 grade neutropenia was more frequent in the PD-L1 inhibitors plus EP group (77.7% vs 69.0%, p= 0.040). Conclusions: In conclusion, the overall efficacy and safety profile was similar between PD-L1 inhibitors and PD-1 inhibitors for the first-line treatment of ES-SCLC.

Molecular imaging research on 18F-FDG PET/CT and biomarker analysis to predict the efficacy of neoadjuvant camrelizumab combined with chemotherapy for resectable stage IIIA-IIIB NSCLC.

e15065 Background: The purpose of this study was to explore the predictive value of tumor and secondary lymphoid metabolic parameters on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and circulating biomarkers for pathological response of neoadjuvant camrelizumab combined with chemotherapy in patients with non-small cell lung cancer (NSCLC). Methods: We included 22 patients who was diagnosed with NSCLC (stage IIIA-IIIB (T3-4N2)) and underwent curative surgery after receiving 3 cycles of camrelizumab plus chemotherapy between January 2023 and January 2024 in Shandong Cancer Hospital. Radical surgery was performed within 4-6 weeks after neoadjuvant therapy. Patients undergo 18F-FDG PET/CT scans in 1 week before treatment and 1 week before surgery. Pathological outcomes were assessed and divided into pathologic complete response (pCR) and non-pCR (defined as residual tumor &gt; 0%). The PET/CT parameters were measured, including tumor metabolic parameters such as maximum normalized uptake value (SUVmax), average normalized uptake value (SUVmean), total pathological glycolysis (TLG), and metabolic tumor volume (MTV). Additionally, secondary lymphoid organ metabolic parameters like the spleno-liver SUVmax ratio (SLR) and bone marrow-liver SUVmax ratio (BLR) were assessed. Furthermore, lymphocyte subsets and inflammatory biomarkers in peripheral blood were analyzed. The correlation between PET/CT metabolic parameters, lymphocyte subsets, inflammatory biomarkers and pathological response was analyzed. Results: pCR was achieved in 8 of the 22 patients. SUVmax in both pCR (p&lt;0.001) and non-pCR patients (p&lt;0.001) decreased before surgery. Among patients with pCR, the absolute value of decreased SUVmax (p = 0.024) and the rate of decreased SUVmax (ΔSUVmax%) (p = 0.042) before surgery was higher than those in non-pCR patients. In pCR group, SLR has a decreasing trend before surgery (p = 0.083). In circulating biomarker analysis, the percentage of NK cells changes (ΔNK%) of patients with pCR before surgery was higher than that of patients with non-pCR (p = 0.029). Neutrophil-to-lymphocyte ratio (NLR) in pCR group decreased significantly (p = 0.021) before surgery and there also had declining trend in the non-pCR group (p = 0.062). Before surgery, systemic immune-inflammation index (SII) was significantly decreased in both pCR (p = 0.028) and non-pCR (p&lt;0.001) groups. There also had significant decrease in derived neutrophil-to-lymphocyte ratio (dNLR) before surgery in both pCR (p = 0.01) and non-pCR (p = 0.031) groups. Conclusions: The SUVmax of the primary site at baseline, ΔSUVmax% and ΔNK% have good value in pCR for patients with stage IIIA-IIIB NSCLC receiving neoadjuvant camrelizumab combined with chemotherapy. More analysis of biomarkers is ongoing.

Effect of strong programmed cell death ligand-1 (PD-L1) expressions on clinical outcomes in advanced non-small cell lung cancer treated with third-generation epidermal growth factor receptor-tyrosine kinase inhibitors.

e20500 Background: Third-generation tyrosine kinase inhibitors (TKIs) are the standard treatment for advanced epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma. In first/second generation EGFR-TKIs, strong programmed death ligand 1 (PD-L1) expression contributes to primary resistance, significantly affecting patient prognosis. Despite this, the relationship between PD-L1 expression levels and third-generation TKIs remains unclear. Methods: This retrospective cohort study reviewed patients with advanced NSCLC who received third-generation EGFR-TKIs as first-line systemic therapy at the Shandong Cancer Hospital between March 2019 and June 2022. The EGFR status of the patients was assessed using amplification refractory mutation system fluorescence quantitative polymerase chain reaction, and the PD-L1 expression level was evaluated using Dako 22 C3 immunohistochemical staining. The Kaplan–Meier method was used for survival analysis. The log-rank test was used to compare differences in survival curves between the two groups. Results: Overall, 150 patients were included in this study. PD-L1 expression was negative (PD-L1 tumor proportion score &lt; 1%) in 89 cases, weak (1–49%) in 42 cases, and strong (≥50%) in 19 cases. The median follow-up period for the entire cohort was 22.12 months (median progression-free survival [mPFS]: 24.33 months); the median overall survival was not reached. mPFS for patients with negative, weak, and strong PD-L1 expressions was 23.60, 26.12, and 16.60 months, respectively. The mPFS for strong PD-L1 expression was significantly shorter than that for with weak PD-L1 expression but was not associated with negativity, particularly in the 19DEL and 21L858R subgroups. PFS was significantly shorter in patients with strong PD-L1 expression in both subgroups (19DEL and 21L858R) than in those with weak PD-L1 expression. Conclusions: Strong PD-L1 expression in tumor cells influenced the clinical outcomes of patients with advanced NSCLC treated with third-generation EGFR-TKIs. Stronger PD-L1 expression in TKI-treated patients with advanced first-line EGFR-mutated NSCLC was associated with worse PFS.

Helical tomotherapy was superior to intensity-modulated radiation therapy in hippocampal avoidance prophylactic cranial irradiation in patients with limited-stage small-cell lung cancer.

e20099 Background: Hippocampal avoidance (HA) techniques have been developed to reduce the risk of neurocognitive dysfunction associated with prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (LS-SCLC). However, applying different radiotherapy techniques to HA has not yet been further analyzed. This study discussed the dosimetric differences between intensity-modulated radiation therapy (IMRT) and helical tomotherapy (TOMO) in HA-PCI and analyzed the benefit of the dosimetric advantage in the risk of brain metastasis (BM) from a clinical perspective. Methods: We retrospectively evaluated patients who underwent PCI from June 2020 to December 2021 at Shandong Cancer Hospital. They were divided according to hippocampal avoidance and radiotherapy techniques: IMRT without HA (non-HA-IMRT), HA-IMRT, and HA-TOMO. The cumulative incidence of BM, target coverage (TC), homogeneity index (HI), conformity index (CI), and hippocampal doses of these radiotherapy programs were evaluated. Results: One hundred seventy-two patients were included in the analysis: 56, 78, and 38 patients in the non-HA-IMRT, HA-TOMO, and HA-IMRT groups, respectively. The 2-year cumulative incidence of BM was 31.4% in patients with HA (78 patients in the HA-TOMO group and 38 patients in the HA-IMRT group) and 23.2% in patients without HA (hazard ratio [HR]: 0.75, 95% confidence interval [95% CI]: 0.43-1.31; P= 0.340). However, the 2-year cumulative incidence of BM was lower in the HA-TOMO group than in the HA-IMRT group (25.0% vs. 44.7%, HR: 0.51, 95% CI: 0.26-0.99; P= 0.029). Both techniques achieved hippocampal protection, but HA-TOMO accomplished significantly better TC (96.24%±0.65% vs. 93.75%±2.45%, P&lt; 0.001), HI (0.09±0.02 vs. 0.27±0.12, P&lt; 0.001), and CI (0.88±0.02 vs. 0.85±0.04, P&lt; 0.001). Conclusions: HA-PCI did not increase BM risk. Additionally, HA-TOMO could achieve better TC, HI, and CI with respect to the planned tumor in the brain while achieving more rapid dosing in the hippocampal region. The cumulative incidence of BM was lower with HA-TOMO than with HA-IMRT.

Genetic characteristics of cerebrospinal fluid-derived circulating tumor DNA in brain metastases of lung adenocarcinoma.

e20503 Background: Brain metastases (BM), encompassing parenchymal metastases (PM) and leptomeningeal metastases (LM), are a common and fatal complication of advanced lung adenocarcinoma (LUAD). However, the genomic disparities between PM and LM, as determined by cerebrospinal fluid (CSF)-derived circulating tumor DNA (ctDNA), and its clinical utility as a liquid biopsy medium remain unclear. Methods: We conducted a retrospective study involving 33 patients diagnosed with BM from LUAD, comprising 16 cases with PM and 17 cases with LM, at Shandong Cancer Hospital between March 2018 and June 2021. CSF and matched peripheral blood lymphocyte samples were collected from all patients, and plasma samples were collected from 25 of them. Genomic profiles of CSF and plasma in patients with PM and LM were compared. CSF-ctDNA, plasma-ctDNA, and DNA from matched peripheral blood lymphocytes underwent next-generation sequencing (NGS) based on a 769 cancer-related gene panel. Results: A total of 363 mutations were detected in CSF-ctDNA, with 90.9% (30/33) of all LUAD patients with PM or LM showing mutations. EGFR mutations were the most common, occurring in PM samples from 56.3% (9/16) of patients and in LM samples from 76.5% (13/17) of patients, followed by other frequently mutated driver genes, including TP53 in 19 (57.6%) patients, MLH1 in 9 (27.3%) patients, and KMT2C in 8 (24.2%). Notably, EGFR 19del was more prevalent as a driver mutation in patients with LM compared to those with PM in our study, particularly the p.E746_A750del mutated subtype. Furthermore, the frequency of mutations in the mismatch repair (MMR) pathway was significantly higher in patients with LM than in those with PM. Additionally, CSF exhibited a more comprehensive profile of driver genomic mutations than matched plasma in patients with any form of BM, accompanied by a higher variation burden and detection of druggable mutations. Conclusions: CSF-ctDNA sequencing revealed distinct genomic patterns in patients with BM, particularly in LM, and could potentially enhance the management of BM patients compared to plasma.

Revolutionizing outcome prediction for immunotherapy with vision transformer-based pathomics signature in esophageal squamous cell cancer.

e16049 Background: Immune checkpoint inhibitors (ICIs) has notably enhanced the survival prospects for patients with esophageal squamous cell carcinoma (ESCC), however the clinical benefit was limited to only a small portion of patients. This study aimed to perform a deep learning signature based on H&amp;E-stained pathological specimens for the purpose of identifying effective markers that can accurately predict the clinical benefit of ICIs among patients with ESCC. Methods: ESCC patients receiving PD-1 inhibitors from Shandong Cancer Hospital were included. Whole slide images (WSIs) of H&amp;E-stained histological specimens of included patients were collected, and subsequently randomly allocated into two sets: a training set comprising 70% of the samples, and a validation set consisting of the remaining 30%. The labels of images were defined by the progression-free survival (PFS) with the interval of 4 months. The pretrained ViT model was used for patch-level model training, and all patches were projected into probabilities after linear classifier. Then the most predictive patches were passed to RNN for final patient-level prediction to construct ESCC-pathomics signature (ESCC-PS). Accuracy rate and survival analysis were performed to evaluate the performance of ViT-RNN survival model in validation cohort. Results: 163 ESCC patients receiving PD-1 inhibitors were included for model training. There were 486,188 patches of 1024*1024 pixels from 324 WSI images of H&amp;E-stained histological specimens after image pre-processing. The training cohort consisted of 120 patients with a total of 227 images, while the validation cohort comprised 43 patients and featured 97 images. Notably, both groups exhibited balanced baseline characteristics between them. The ESCC-PS achieved an accuracy of 84.5% in the validation cohort, and could distinguish patients into three risk groups with the median PFS of 2.7, 4.8 and 16.7 months (P &lt; 0.001). The multivariate cox analysis revealed ESCC-PS could act as an independent predictor of survival from PD-1 inhibitors (P &lt; 0.001). A combined signature incorporating ESCC-PS and expression of PD-L1 shows significantly improved accuracy in outcome prediction of PD-1 inhibitors compared to ESCC-PS and PD-L1 anlone, with the area under curve value of 0.952, 0.924, 0.648 for 6-month PFS and C-index of 0.816, 0.806, 0.66, respectively. Conclusions: The outcome supervised pathomics signature based on deep learning has the potential to enable superior prognostic stratification of ESCC patients receiving PD-1 inhibitors, which convert the images pixels to an effective and labour-saving tool to optimize clinical management of ESCC patients.

The incidence of and risk factors for radiation pneumonitis in patients treated with simultaneous bevacizumab and thoracic radiotherapy

BackgroundFirst-line chemotherapy combined with bevacizumab is one of the standard treatment modes for patients with advanced non-small cell lung cancer (NSCLC). Thoracic radiotherapy (TRT) can provide significant local control and survival benefits to patients during the treatment of advanced NSCLC. However, the safety of adding TRT has always been controversial, especially because of the occurrence of radiation pneumonia (RP) during bevacizumab treatment. Therefore, in this study, we used an expanded sample size to evaluate the incidence of RP when using bevacizumab in combination with TRT.Patients and methodsUsing an institutional query system, all medical records of patients with NSCLC who received TRT during first-line chemotherapy combined with bevacizumab from 2017 to 2020 at Shandong Cancer Hospital and Institute were reviewed. RP was diagnosed via computed tomography and was classified according to the RTOG toxicity scoring system. The risk factors for RP were identified using univariate and multivariate analyses. The Kaplan–Meier method was used to calculate progression-free survival (PFS) and overall survival (OS).ResultsUltimately, 119 patients were included. Thirty-eight (31.9%) patients developed Grade ≥ 2 RP, of whom 27 (68.1%) had Grade 2 RP and 11 (9.2%) had Grade 3 RP. No patients developed Grade 4 or 5 RP. The median time for RP occurrence was 2.7 months (range 1.2–5.4 months). In univariate analysis, male, age, KPS score, V20 > 16.9%, V5 > 33.6%, PTV (planning target volume)-dose > 57.2 Gy, and PTV-volume > 183.85 cm3 were correlated with the occurrence of RP. In multivariate analysis, male, V20 > 16.9%, and PTV-volume > 183.85 cm3 were identified as independent predictors of RP occurrence. The mPFS of all patients was 14.27 (95% CI, 13.1–16.1) months. The one-year and two-year PFS rates were 64.9% and 20.1%, respectively. The mOS of all patients was 37.09 (95% CI, 33.8–42.0) months. The one-year survival rate of all patients was 95%, and the two-year survival rate was 71.4%.ConclusionsThe incidence of Grade ≥ 2 RP in NSCLC patients who received both bevacizumab and TRT was 31.9%. Restricting factors such as V20 and PTV will help reduce the risk of RP in these patients. For patients who receive both bevacizumab and TRT, caution should be exercised when increasing TRT, and treatment strategies should be optimized to reduce the incidence of RP.

Nomograms for metastasis of non-sentinel lymph nodes or more than three lymph nodes in patients with one or two positive sentinel lymph nodes.

The purpose of this study was to provide advice for the indication of regional nodal irradiation (RNI) in patients with one to two positive sentinel lymph nodes (SLNs) without axillary lymph node dissection (ALND). We conducted a retrospective study in Shandong Cancer Hospital, Fudan University Shanghai Cancer Center, and West China Hospital. Logistic analysis was performed in order to explore the influencing factors of positive non-SLNs (NSLNs) and >3 positive nodes among patients with one to two SLNs+. Then, nomograms were constructed. Between May 2010 and 2020, among the 2,845 patients with one to two SLNs+ undergoing ALND (1,992 patients in the training set and 853 patients in the validation set), there were 34.3% harbored NSLNs+ and 15.6% harbored >3 positive nodes. Multivariate analysis showed that cN stage, the number of positive/negative SLN, pathological tumor stage, lympho-vascular invasion (LVI), multicenter, and molecular subtypes were significantly associated with NSLN metastasis. Similarly, multivariate analysis also showed that cN stage, the number of positive/negative SLNs, pathological tumor stage, and LVI could be independent predictors of >3 positive nodes. Then, nomograms for NSLN metastasis and >3 positive nodes were constructed using these parameters, respectively. The nomograms will be useful in estimating positive NSLNs and >3 positive nodes, and they might provide advice for the optimization of RNI.

An investigation of the advantages of the adjustable angle stitch template compared with CT-guided 125I seeds free-hand implantation in the treatment of non-small cell lung carcinoma

Objective: To investigate the advantages of adjustable angle needle path template compared with CT-guided 125I seeds free-hand implantation in the treatment of non-small cell lung carcinoma. Methods: This randomized controlled trial involved the retrospective analysis of the clinical data of 45 patients with non-small cell lung carcinoma who underwent 125I seeds implantation at the Shandong Cancer Hospital, Shaanxi Provincial Tumor Hospital and The Third Affiliated Hospital of Shandong First Medical University from May 2018 to January 2023. Patients were divided into the template (n=21) and free-hand (n=24) groups, according to the modality used. The template group comprised 16 males and 5 females, aged (66±12) years, while the free-hand group comprised 16 males and 8 females, aged (62±8) years. The dose distribution, implant quality, intraoperative computed tomography (CT) scan times, and 125I seed reseeding numbers after implantation were compared between the two groups to evaluate the potential advantages of adjustable angle needle path template-assisted implantation over free-hand 125I implantation. Results: Statistical comparison revealed no significant differences in age (t=1.16, P=0.253), tumor volume [(71±26) vs. (71±22) cm3, t=0.21, P=0.837), or any other baseline characteristics between the template and free-hand groups. Overall, 45 patients successfully completed the operation. In the template group, the mean values of the D90 (dose that was delivered to 90% of the target volume), V100 (the target volume receiving 100% of the prescription dose), coverage index (CI), relative dose homogeneity index (HI), and external volume index (EI) pre-and post-implantation were (131.0±2.1) vs. (131.1±5.5) Gy, 90.0%±0.4% vs. 91.0%±2.8%, 0.83±0.07 vs. 0.82±0.05, 41%±11% vs. 37%± 13%, and 4.3%(2.9%, 14.0%) vs.8.8%(5.2%,14.6%), respectively. None of these parameters showed any significant difference (all P>0.05). In the free-hand group, the mean value of D90 pre- and post-implantation was (131.4±2.9) vs.(128.6±8.6) Gy, showing no significant difference (P>0.05), the mean values of V100, CI, HI, and EI pre-and post-implantation were 90.0%±0.5% vs. 89.0%± 3.0%, 0.84±0.04 vs. 0.71±0.09, 41%±9% vs. 34%±10%, and 7.7% (4.9%,11.0%) vs.24.2% (14.3%, 35.3%), respectively, showing significant differences (all P<0.05). The number of reseeding seeds in the template group was lower than that in the free-hand group [2.0 (0,2.5) vs. 4.0 (2.0, 7.0), Z=-3.36, P=0.001], showing a statistically significant difference. Further, the number of CT scans in the template group was significantly less than that in the free-hand group (3.9±0.5 vs. 4.6±1.2, t=-2.54, P=0.016). The incidences of adverse reactions were 23.8% (5/21) and 33.3% (8/24) (χ2=12.86, P=0.002) in the template and free-hand groups, respectively, indicating a significant difference. Conclusion: Compared with free-hand implantation, use of the adjustable angle needle path template technique can shorten the operation time, reduce the number of scans, reduce the incidence of complications, and improve treatment efficacy to a certain extent.

Phase I/II clinical trial of efficacy and safety of EGCG oxygen nebulization inhalation in the treatment of COVID-19 pneumonia patients with cancer

BackgroundThe antiviral drug Nirmatrelvir was found to be a key drug in controlling the progression of pneumonia during the infectious phase of COVID-19. However, there are very few options for effective treatment for cancer patients who have viral pneumonia. Glucocorticoids is one of the effective means to control pneumonia, but there are many adverse events. EGCG is a natural low toxic compound with anti-inflammatory function. Thus, this study was designed to investigate the safety and efficacy of epigallocatechin-3-gallate (EGCG) aerosol to control COVID-19 pneumonia in cancer populations.MethodsThe study was designed as a prospective, single-arm, open-label phase I/II trial at Shandong Cancer Hospital and Institute, between January 5, 2023 to March 31,2023 with viral pneumonia on radiographic signs after confirmed novel coronavirus infection. These patients were treated with EGCG nebulization 10 ml three times daily for at least seven days. EGCG concentrations were increased from 1760-8817umol/L to 4 levels with dose escalation following a standard Phase I design of 3–6 patients per level. Any grade adverse event caused by EGCG was considered a dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) is defined as the highest dose with less than one-third of patients experiencing dose limiting toxicity (DLT) due to EGCG. The primary end points were the toxicity of EGCG and CT findings, and the former was graded by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0. The secondary end point was the laboratory parameters before and after treatment.ResultA total of 60 patients with high risk factors for severe COVID-19 pneumonia (factors such as old age, smoking and combined complications)were included in this phase I-II study. The 54 patients in the final analysis were pathologically confirmed to have tumor burden and completed the whole course of treatment. A patient with bucking at a level of 1760 umol/L and no acute toxicity associated with EGCG has been reported at the second or third dose gradients. At dose escalation to 8817umol/L, Grade 1 adverse events of nausea and stomach discomfort occurred in two patients, which resolved spontaneously within 1 hour. After one week of treatment, CT showed that the incidence of non-progression of pneumonia was 82% (32/39), and the improvement rate of pneumonia was 56.4% (22/39). There was no significant difference in inflammation-related laboratory parameters (white blood cell count, lymphocyte count, IL-6, ferritin, C-reactive protein and lactate dehydrogenase) before and after treatment.ConclusionAerosol inhalation of EGCG is well tolerated, and preliminary investigation in cancer population suggests that EGCG may be effective in COVID-19-induced pneumonia, which can promote the improvement of patients with moderate pneumonia or prevent them from developing into severe pneumonia.Trial registrationClinicalTrials.gov Identifier: NCT05758571. Date of registration: 8 February 2023.

Prognostic implications of combining EGFR-TKIs and radiotherapy in Stage IV lung adenocarcinoma with 19-Del or 21-L858R mutations: A real-world study.

To elucidate the potential benefits of combining radiotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for individuals with Stage IV lung adenocarcinoma (LUAD) harboring either exon 19 deletion (19-Del) or exon 21 L858R mutation (21-L858R). In this real-world retrospective study, 177 individuals with Stage IV LUAD who underwent EGFR-TKIs and radiotherapy at Shandong Cancer Hospital from June 2012 to August 2017 were included. The main focus of this real-world study was overall survival (OS). The clinical characteristics of patients with Stage IV LUAD harboring 19-Del were similar to those harboring 21-L858R (p > 0.05). Overall, the patients had a median OS (mOS) of 32.0 months (95% confidence interval [CI]: 28.6-35.5). Subsequently, multivariate analysis indicated that both EGFR mutations and thoracic radiotherapy were independent predictors of OS (p = 0.001 and 0.013). Furthermore, subgroup analysis highlighted a longer OS for the 19-Del group compared to the 21-L858R group, especially when EGFR-TKIs were combined with bone metastasis or thoracic radiotherapy (mOS: 34.7 vs. 25.1 months and 51.0 vs. 29.6 months; p = 0.0056 and 0.0013, respectively). However, no significant differences were found in OS when considering patients who underwent brain metastasis radiotherapy (mOS: 34.7 vs. 25.1 months; p = 0.088). Patients with Stage IV LUAD harboring 19-Del experience a notably prolonged OS following combined therapy with EGFR-TKIs and radiotherapy, while this OS benefit is observed despite the absence of substantial differences in the clinical characteristics between the 19-Del and 21-L858R groups.