Comparison of the effectiveness of chemotherapy combined with immunotherapy and chemotherapy alone in advanced biliary tract cancer and construction of the nomogram for survival prediction based on the inflammatory index and controlling nutritional status score.

OBJECTIVE: To analyze the effectiveness of combining immune checkpoint inhibitors (ICIs) with first-line therapy in patients with advanced biliary tract cancer (BTC) and explore the biomarkers affecting the prognosis of immunotherapy, to construct a nomogram for the prediction of survival. METHODS: A retrospective study was conducted to include a total of 209 patients with advanced BTC treated in the first line from 2018 to 2022, divided into a combination therapy group (n = 129) and a chemotherapy-only group (n = 80) according to whether ICIs were applied in combination. Univariate and multifactorial COX regression analyses were performed on variables that may affect prognosis to identify independent influences on patient prognosis, and this was used to create nomograms, which were then prospectively validated and calibrated. RESULTS: The median progression-free survival (mPFS) and median overall survival (mOS) of patients in the combination therapy group were higher than those in the chemotherapy alone group [hazard ratio (HR) = 1.152, 95% confidence interval (CI): 0.7848-1.692, p = 0.0004, and HR = 1.067, 95% CI: 0.7474-1.524, p = 0.0016]. The objective response rate (ORR) of patients in the combination therapy and chemotherapy alone groups was 39.5% (51/129) vs. 27.5% (22/80), and the disease control rate (DCR) between the two groups was 89.9% (116/129) vs. 83.8% (67/80). Univariate analysis revealed the gender, presence of long-term tobacco and alcohol, degree of histological differentiation, serum albumin level, presence of liver metastases, presence of multi-visceral metastases, response, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), glycoprotein antigen 19-9 (CA19-9), systemic inflammatory index (SII), and controlling nutritional status (CONUT) scores were statistically significant with patient prognosis (all P values < 0.05). Multi-factor COX regression analysis was continued for the above variables, and the results showed that NLR, MLR, PLR, SII, and CONUT scores were independent influences on patients' OS (all p values < 0.05). A nomogram (C-index 0.77, 95% CI: 0.71-0.84) was created based on these independent influences and later validated using a validation cohort (C-index 0.75, 95% CI: 0.68-0.81). The time-dependent receiver operator characteristic curve (ROC) showed that the area under curve (AUC) of the training cohort patients at 12, 18, and 24 months was 0.72 (95% CI: 0.63-0.81), 0.75 (95% CI: 0.67-0.85), and 0.77 (95% CI: 0.66-0.87) and the AUC of the validation cohort was 0.69 (95% CI: 0.58-0.79), 0.74 (95% CI: 0.65-0.87), and 0.71 (95% CI: 0.64-0.89), respectively. Finally, calibration was performed using calibration curves, and the results showed that nomograms based on inflammatory metrics and CONUT scores could be used to assess survival (12, 18, and 24 months) in patients with advanced BTC treated with ICIs in the first line. CONCLUSION: Patients with advanced BTC benefit more from first-line treatment with standard chemotherapy in combination with ICIs than with chemotherapy alone. In addition, nomograms based on inflammatory metrics and CONUT scores can be used to predict survival at 12, 18, and 24 months in patients with advanced BTC treated with ICIs.

PD-1 Inhibitors Combined with Tyrosine Kinase Inhibitors with or without Hepatic Artery Infusion Chemotherapy for the First-Line Treatment of HBV-Related Advanced Hepatocellular Carcinoma: A Retrospective Study.

Purpose: Comparing the efficacy and safety of programmed cell death protein-1 (PD-1) inhibitors combined with tyrosine kinase inhibitors (TKIs) with or without hepatic artery infusion chemotherapy (HAIC) in HBV-related advanced HCC and exploring prognostic predictors of the combined regimen. Patients and Methods: A total of 194 patients diagnosed with HBV-related advanced HCC between 2020 and 2022 were included in the study, including 99 in the HAIC combined with PD-1 inhibitors plus TKIs (HPT group) and 95 in the PD-1 inhibitors plus TKIs (PT group). The efficacy was evaluated according to the tumor response rate and survival, and the safety was evaluated according to the adverse events. Results: The HPT group showed higher overall response rate and disease control rate than the PT group. The median overall survival (OS) of the HPT group and the PT group were 18.10 months and 12.57 months, respectively, and the difference was statistically significant (hazard ratio (HR) = 0.519, 95% confidence interval (CI): 0.374-0.722, P < 0.001). The median progression-free survival (PFS) was 9.20 months in the HPT group and 6.33 months in the PT group (HR = 0.632, 95% CI: 0.470-0.851, P = 0.002). In addition, albumin bilirubin (ALBI) and systemic inflammatory response index (SIRI) are independent prognostic factors affecting HAIC combined with targeted immunotherapy and can be used as prognostic predictors. Almost all patients included in the study experienced treatment-related adverse events (TRAEs) of varying degrees of severity, with grade 1-2 adverse events predominating. Conclusion: The HPT group had better OS and PFS than the PT group in patients with HBV-related advanced HCC. In addition, high ALBI and high SIRI were associated with poor prognosis in the HAIC combined group.

Recent advances in natural polysaccharides against hepatocellular carcinoma: A review.

Hepatocellular carcinoma (HCC) is a malignant tumor of the digestive system that poses a serious threat to human life and health. Chemotherapeutic drugs commonly used in the clinic have limited efficacy and heavy adverse effects. Therefore, it is imperative to find effective and safe alternatives, and natural polysaccharides (NPs) fit the bill. This paper summarizes in detail the anti-HCC activity of NPs in vitro, animal and clinical trials. Furthermore, the addition of NPs can reduce the deleterious effects of chemotherapeutic drugs such as immunotoxicity, bone marrow suppression, oxidative stress, etc. The potential mechanisms are related to induction of apoptosis and cell cycle arrest, block of angiogenesis, invasion and metastasis, stimulation of immune activity and targeting of MircoRNA. And on this basis, we further elucidate that the anti-HCC activity may be related to the monosaccharide composition, molecular weight (Mw), conformational features and structural modifications of NPs. In addition, due to its good physicochemical properties, it is widely used as a drug carrier in the delivery of chemotherapeutic drugs and small molecule components. This review provides a favorable theoretical basis for the application of the anti-HCC activity of NPs.

Efficacy and safety analysis of chemotherapy combined with immunotherapy compared with standard chemotherapy for advanced biliary tract malignant tumors.

OBJECTIVE: The treatment of biliary tract (BTC) cancer remains relatively limited, especially in the setting of advanced BTC. Immune checkpoint inhibitors (ICIs) have shown some effects in a variety of solid tumors, but their efficacy and safety in patients with advanced BTC are still elusive, which require in-depth analysis. METHODS: The clinical information of 129 patients diagnosed with advanced BTC between 2018 and 2021 were retrospectively reviewed. All patients were treated with chemotherapy, while a portion of them (64 patients) were treated with ICIs, the other 64 patients were not. Therefore, we divided the patients into two groups, SC (standard chemotherapy) and CI (chemotherapy in combined with immunotherapy), then we analyzed the benefit of adding ICIs according to efficacy, adverse events, progression-free survival (PFS), progressive disease (PD), and the influence of various factors and effectiveness. RESULTS: The mean PFS was 9.67 months for CI group and 6.83 months for SC group. The PFS was prolonged by 2.84 months with ICI addition, and the difference was statistically significant (t = 3.114, 95% CI: 1.06-4.74, p < 0.001). The objective response rate (ORR) was 32.81% (21/64) for the CI group versus 10.77% (7/65) for the SC group, and the disease control rate (DCR) was 79.69% (51/64) versus 67.69% (44/65), respectively. Regression analysis showed that factors such as changes in CA19-9, the level of PD-L1 expression, tobacco and alcohol, and the neutrophil-lymphocyte (NLR) ratio all influenced PFS (p < 0.05 for all these factors). For the treatment-related adverse events (TRAEs), the highest grade 3-4 adverse effects were thrombocytopenia in 7.75% (10/129) and neutropenia in 3.1% (4/129), immune-related adverse events (irAEs) occurred in 32.8% (21/64), and all were grade 1-2. CONCLUSIONS: Our results showed that ICIs combined with chemotherapy exhibited good antitumor activity with acceptable safety and could be recommended as first-line treatment for patients with advanced BTC.

Retrospective study of the combination of TP and PF regimens with or without immune checkpoint inhibitors for the first-line treatment of locally advanced or advanced esophageal squamous cell carcinoma.

Objective: To investigate the efficacy and safety differences between the cisplatin + paclitaxel (TP) and cisplatin + fluorouracil (PF) regimens in combination with or without immune checkpoint inhibitors (ICIs) in advanced esophageal squamous cell carcinoma (ESCC) first-line treatment and prognostic factors. Methods: We selected the medical records of patients with late stage ESCC admitted to the hospital between 2019 and 2021. Based on the first-line treatment regimen, control groups were divided into chemotherapy plus ICIs (n = 243) and non-ICIs (n = 171), 119 (49%) in the TP + ICIs group, 124 (51%) in the PF + ICIs group, 83 (48.5%) in the TP group, and 88 (51.5%) in the PF group in the control group. We analyzed and compared factors related to efficacy, safety, or response to toxicity and prognosis across four subgroups. Results: The overall objective response rate (ORR) and disease control rate (DCR) of the TP plus ICIs group were 42.1% (50/119) and 97.5% (116/119), respectively, which were 6.6% and 7.2% higher than those of the PF plus ICIs group. Patients in the TP combined with ICIs group had higher overall survival (OS) and progression-free survival (PFS) than those in the PF combined with ICIs group [hazard ratio (HR) = 1.702, 95% confidence interval (CI): 0.767-1.499, p = 0.0167 and HR = 1.158, 95% CI: 0.828-1.619, p = 0.0055] ORR and DCR were 15.7% (13/83) and 85.5% (71/83) in the TP chemotherapy alone group, significantly higher than the PF group [13.6% (12/88) and 72.2% (64/88)] (p < 0.05), OS and PFS were also better in patients treated with TP regimen chemotherapy than PF (HR = 1.173, 95% CI: 0.748-1.839, p = 0.0014 and HR = 0.1.245, 95% CI: 0.711-2.183, p = 0.0061). Furthermore, following the combination of TP and PF diets with ICIs, the OS of the patients was higher than that of the group treated with chemotherapy alone (HR = 0.526, 95% CI: 0.348-0.796, p = 0.0023 and HR = 0.781, 95% CI: 0.0.491-1.244, p < 0.001). Regression analysis showed that the neutrophil-to-lymphocyte ratio (NLR), the control nuclear status score (CONUT), and the systematic immune inflammation index (SII) were independent prognostic factors for the efficacy of immunotherapy (p < 0.05). The overall incidence of treatment-associated adverse events (TRAEs) was 79.4% (193/243) and 60.8% (104/171) in the experimental and control groups, respectively, and there was no statistically significant difference in TRAEs between TP + ICIs (80.6%) and PF + ICIs (78.2%) (61.4%) and PF groups (60.2%) (p > 0.05). Overall, 21.0% (51/243) of patients in the experimental group experienced immune-related adverse events (irAEs), and all of these adverse effects were tolerated or remitted following drug treatment without affecting follow-up. Conclusion: The TP regimen was associated with better PFS and OS with or without ICIs. Furthermore, high CONUT scores, high NLR ratios, and high SII were found to be associated with poor prognosis in combination immunotherapy.

Case Report: A case of advanced duodenal adenocarcinoma in complete remission after chemotherapy combined with targeted therapy and radiotherapy.

Duodenal adenocarcinoma (DA) is an extremely rare and highly aggressive malignant tumor of the digestive system. Due to the lack of specific clinical characteristics, it is easy to misdiagnosis and miss diagnosis, and the lack of specific consensus and recommendation for treatment, so it often refers to stomach cancer and colorectal cancer. Now, we report a case of a patient with advanced DA who achieved complete remission (CR) after undergoing chemoradiotherapy combined with targeted therapy. The patient was pathologically diagnosed with DA after radical surgery in October 2020, and he failed to undergo adjuvant chemotherapy on time due to the COVID-19 outbreak. The patient found multiple lymph node liver and abdominal metastases 6 months after the operation. Considering the progression of the disease, XELOX regimen (oxaliplatin + capecitabine) chemotherapy was given for 1 cycle. After 1 cycle of treatment, the tumor markers remained elevated; the carcinoembryonic antigen (CEA) was 5.03 ng/ml (0-5 ng/ml), and the carbohydrate antigen 19-9 (CA19-9) was 747.30 U/ml (0-37 U/ml). The patient also developed intolerable capecitabine-related treatment-related adverse events (TRAEs), namely, hand-foot syndrome. For the above reasons, capecitabine was replaced as S-1 at cycle 2, and the chemotherapy regimen became SOX (oxaliplatin + S-1); bevacizumab injection was also added to the SOX regimen, and it was further treated regularly for 7 cycles with the regimen of SOX plus bevacizumab. Liver metastases showed a continuous narrowing trend throughout the treatment period; tumor markers also showed a downward trend. Finally, the patient achieved complete remission (CR) at cycle 7. After completion of chemotherapy, radiotherapy was administered to the resistant metastatic lymph nodes present in the patient's abdominal cavity for a total of 10 times. However, the patient developed severe bone marrow suppression and obstructive jaundice during the course of radiotherapy and finally failed to complete the radiotherapy plan. Currently, the patient continued maintenance therapy with bevacizumab and S-1 and showed no recurrence or metastasis after review. In this case of advanced DA, we referred to both CRC and gastric cancer in the treatment regimen of the patient. At the same time, targeted drugs and radiotherapy were also added to the basis of chemotherapy, which has no clear consensus recommendation or case for reference in the treatment of advanced DA. Thankfully, the patient's disease was controlled and remained stable after treatment with this regimen. Therefore, for patients with advanced DA who lack standardized treatment regimens and guidelines, the combination of chemotherapy with targeted therapy and radiotherapy may be one of the effective treatment modalities.