Adjuvant Therapy In Patients Research Articles

The impact of preoperative renal insufficiency on the outcomes of patients with pancreatic cancer undergoing pancreaticoduodenectomy.

This study evaluated the impact of renal function impairment on long-term survival outcomes and adjuvant therapy in patients with pancreatic cancer undergoing pancreaticoduodenectomy (PD). In this study, 264 patients who underwent PD for pancreatic head cancer between 2011 and 2021 were retrospectively analyzed. The patients were subsequently categorized into three groups according to the estimated glomerular filtration rate: normal group (> 90 mL/min/1.73 m2, n = 73), moderate group (45-90 mL/min/1.73 m2, n = 176), and severe group (< 45 mL/min/1.73 m2, n = 15). The primary outcomes evaluated were postoperative complications, overall survival (OS), and relapse-free survival (RFS). Additionally, the completion of adjuvant therapy and risk factors for adjuvant therapy discontinuation were analyzed. The total proportion of patients with complications was significantly higher in the severe group (p = 0.008). The proportion of patients with severe complications (Clavien-Dindo classification ≥ IIIa) did not significantly differ between the chronic kidney disease (CKD) groups (p = 0.730). The proportion of patients in whom adjuvant therapy was completed was notably lower in the severe group (p = 0.011). Multiple logistic regression analysis revealed that CKD groups and hemoglobin levels ≤ 11.5g/dL were independent predictors of adjuvant therapy completion failure (p = 0.016 and p = 0.016). There was no significant difference in the OS and RFS rates between the CKD groups (p = 0.499, p = 0.688). In patients with pancreatic cancer and CKD, performing PD safely may be feasible; however, adjuvant therapy completion is challenging.

Effect of ethyl acetate extract from Usnea longissima on chemotherapy-associated multiple organ dysfunction in rats

BackgroundThe toxic effects of doxorubicin and cisplatin in various organs have been associated with oxidative stress. Studies have shown that Usnea longissima has strong antioxidant effects. This study aimed to investigate the protective effect of ethyl acetate extract from Usnea longissima (ULE), which is known to have strong antioxidant effects, on chemotherapeutic-induced heart, kidney, liver, and ovarian toxicity. MethodsAlbino Wistar female rats were divided into five groups (12 rats per group): healthy (HG), doxorubicin (DOX), Cisplatin (CIS), Doxorubicin+ ULE (DULE), Cisplatin+ ULE (CULE). In this experiment, ULE was given 100 mg/kg orally. After 1 hour, 2.5 mg/kg doxorubicin and 2.5 mg/kg cisplatin were administered intraperitoneally. Drug treatments continued once a day for seven days. At the end of seven days, six rats from each group were euthanized and heart, kidney, liver, and ovary tissues were analyzed biochemically. The remaining rats were left in the laboratory with male rats for 45 days for reproduction. ResultsULE inhibited chemotherapeutic-induced increase in malondialdehyde, tumor necrosis factor-alpha, and interleukin 6 and a decrease in total glutathione in liver, kidney, and ovarian tissues. ULE also inhibited the increase of blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase in serum. ULE treatment had no protective effect against doxorubicin and cisplatin cardiac toxicity. On the other hand, ULE also decreased the delay in pregnancy induced by chemotherapy. ConclusionULE may be considered an adjuvant therapy in patients receiving chemotherapy to reduce liver, kidney, and ovarian toxicity.

Repurposing celecoxib as adjuvant therapy in patients with Parkinsonian disease: a new therapeutic dawn: randomized controlled pilot study.

The clinical presentations of Parkinson's disease (PD), a chronic neurodegenerative condition, include bradykinesia, hypokinesia, stiffness, resting tremor, and postural instability. Recently, neuroinflammation is involved in pathogenesis of PD. Application of nonsteroidal anti-inflammatory drugs captured attention to treat these neuroinflammation. To investigate the possible effectiveness of celecoxib in patients with PD treated with conventional treatment. Sixty outpatients who fulfilled the inclusion requirements for PD were enrolled in this randomized, prospective, and controlled study. The patients were allocated into two groups at random (n = 30); the control group received standard PD treatment, consisting of levodopa/carbidopa, and the celecoxib group received standard PD treatment plus celecoxib. A neurologist evaluated each patient at the beginning of the treatment and after 6months. Assessment of Unified Parkinson's disease rating scale (UPDRS) for each patient. Before and after treatment, α -synuclein (α-Syn), tumor necrosis factor alpha (TNF-α), Toll like receptors-4 (TLR-4), nuclear factor erythroid 2-related factor 2 (Nrf-2) and brain-derived neurotropic factor (BDNF) were assessed. Paired and unpaired t tests were used to assess statistical significance within and between groups respectively. The celecoxib group exhibited a significant and statistical reduction in the level of measured parameters by unpaired t test as followed: TLR-4 (p = 0.004), TNF-α (p = 0.042), and α-Syn (p = 0.004) apart from a significant increase in BDNF (p = 0.0005) and Nrf-2 (p = 0.004), in comparison with the control group. Also, UPDRS was significantly decreased in celecoxib group (p < 0.05). Celecoxib could be a promising adjuvant therapy in managing patients with PD. NCT05962957.

Survival outcomes of neoadjuvant versus adjuvant therapy in patients with T1c, node‐negative, human epidermal growth factor receptor 2–positive breast cancer: A Surveillance, Epidemiology, and End Results population‐based study

AbstractBackgroundPersistent debates exist regarding the superiority of neoadjuvant therapy (NAT) over adjuvant therapy (AT) for patients with T1c, node‐negative, human epidermal growth factor receptor 2–positive (HER2+) breast cancer, and relevant guidelines for these patients are lacking.MethodsData on patients with T1cN0M0‐stage HER2+ breast cancer who received chemotherapy and surgery were extracted from 2010 to 2020 from the Surveillance, Epidemiology, and End Results database. Propensity score matching (PSM) was used to create well‐balanced cohorts for the NAT and AT groups. Kaplan–Meier (KM) analysis and Cox proportional hazards models were used to assess the differences between NAT and AT in terms of overall survival (OS) and breast cancer–specific survival (BCSS). Additionally, logistic regression models were used to explore factors associated with response to NAT.ResultsAfter PSM, 2140 patient pairs were successfully matched, which achieved a balanced distribution between the NAT and AT groups. KM curves revealed similar OS and BCSS between patients receiving NAT and those undergoing AT. A multivariate Cox model identified achieving pathological complete response (pCR) after NAT, compared with AT, as a protective prognostic factor for OS (hazard ratio, 0.52; 95% CI, 0.35–0.77; p &lt; .001) and BCSS (hazard ratio, 0.60; 95% CI, 0.37–0.98; p = .041). A logistic regression model revealed that White race and hormone receptor–negative status independently predicted pCR.ConclusionsFor patients with T1cN0M0‐stage HER2+ breast cancer, NAT demonstrated comparable OS and BCSS to AT. Patients who achieved pCR after NAT exhibited significantly better survival outcomes compared with those who received AT.

Effectiveness of autologous mononuclear cells as adjuvant therapy in patients with ischaemic diabetic foot ulcers receiving indirect lower limb revascularization.

The current study aimed to evaluate the effectiveness of peripheral blood mononuclear cells (PB-MNCs) therapy for patients with ischaemic diabetic foot ulcers (DFUs) treated through indirect revascularization. The study is a prospective non-controlled observational study including patients with neuro-ischaemic DFUs who received indirect peripheral revascularization and showed a persistence of wound ischaemia defined by the absence of angiographic collateral vessels and TcPO2 values < 30mmHg in the wound angiosome area. All patients received 3 cycles of PB-MNCs therapy administered along the wound related artery based on the angiosome theory. The primary outcomes measures were healing, major amputation, and survival after 1year of follow-up. The secondary outcomes measures were the evaluation of tissue perfusion by TcPO2 and foot pain defined by the Numerical Rating Scale (NRS). Overall 52 (9.7%) patients were included. Most patients were aged (> 70years), all of them were affected by Type 2 Diabetes with a long diabetes duration (> 20years). Almost 80% were assessed as grade 2D- 3D of Texas University Classification. Forty-four patients (84.6%) patients healed and survived, 2 (3.85%) healed and deceased, 2 (3.85%) not healed and deceased, 4 (7.7%) not healed and survived. No major amputations were recorded. A significant increase of TcPO2 after PB-MNCs therapy were recorded in comparison to the baseline (43 ± 9 vs 18 ± 8mmHg, p < 0.0001), such asa concomitant reduction of foot pain (1.8 ± 1.2 vs 6.2 ± 2.1, p < 0.0001). PB-MNCs resulted effective to promote wound healing and limb salvage in diabetic patients with ischaemic DFUs who received indirect revascularization.

Potential of Vitamin D and l-Cysteine Co-supplementation to Downregulate Mammalian Target of Rapamycin: A Novel Therapeutic Approach to Diabetes.

Diabetes, a metabolic disease associated with an increased health care burden and mortality, is currently on the rise. Both upregulation of the mammalian target of rapamycin (mTOR) and decreased levels of vitamin D (VD) and l-cysteine (LC) have been associated with diabetes. The overactivation of mTOR leads to insulin desensitization and metabolic dysfunction including uncontrolled hyperglycemia. This review summarizes various studies that have shown an inhibitory effect of VD or LC on mTOR activity. Findings from preclinical studies suggest that optimizing the VD and LC status in patients with diabetes can result in mTOR suppression, which has the potential to protect these individuals from microvascular and macrovascular complications while enhancing the regulation of their blood glucose. Given this information, finding ways to suppress mTOR signaling and also increasing VD and LC status is a possible therapeutic approach that might aid patients with diabetes. Future clinical trials are needed to investigate whether VD and LC co-supplementation can successfully downregulate mTOR and can be used as adjuvant therapy in patients with diabetes.

Real-world effectiveness of adjuvant octreotide therapy in patients with pancreatic neuroendocrine tumors at high recurrence risk: A multicenter retrospective cohort study.

Adjuvant therapy for pancreatic neuroendocrine tumors (PanNETs) after radical resection lacks evidence-based data and remains controversial. This study aimed to validate whether long-acting octreotide is a potential candidate for adjuvant therapy in patients with G2 PanNETs at high recurrence risk by clustering real-world data. A retrospective review of patients with nonmetastatic grade 2 PanNETs who underwent radical resection at six research centers between 2008 and 2020 was conducted. Propensity score matching and inverse probability of treatment weight analysis were used to control confounding factors. Overall, 357 patients (octreotide group, n = 82; control group, n = 275) were analyzed. Kaplan-Meier survival analyses showed that the octreotide group had longer disease-free survival (DFS) compared with the control group (36 months: 93.3% vs. 79.0%, p = .0124; 60 months: 71% vs. 67.6%, p = .0596, respectively), as well as overall survival (OS) (60 months: 98% vs. 83.8%, p = .0117, respectively). Multivariate analyses indicated that octreotide long-acting repeatable (LAR) adjuvant therapy was associated with higher OS (p = .0270) at 60 months. Propensity score matching analysis showed that octreotide adjuvant therapy was associated with higher DFS (p = .0455) and OS (p = .0190) at 60 months. Similar results were obtained via inverse probability of treatment weight analysis. Subgroup analysis indicated that octreotide LAR was associated with a high DFS in patients with lymph node metastasis or Ki-67 <10% PanNETs. Adjuvant therapy with long-acting octreotide following radical resection of nonmetastatic G2 PanNETs may be associated with improved DFS and OS in a real-world setting.

Ginseng Radix et Rhizoma enhanced the effect of metoprolol in chronic heart failure by inhibiting autophagy in male C57BL/6J mice.

Ginseng Radix et Rhizoma (GS) is frequently used as an adjuvant therapy for patients with heart failure (HF). Metoprolol is widely used in patients with HF. However, there is no report on the combined effects of GS and metoprolol in patients with HF. This study investigated the combined effects of GS and metoprolol in male C57BL/6J mice with HF and the underlying mechanisms. We utilized a mouse myocardial HF model to measure the serum levels of creatine kinase (CK) and creatine kinase-MB form (CK-MB) using an automated biochemical analyzer. Lactate dehydrogenase (LDH) and cardiac troponin (cTnT) levels were determined using enzyme-linked immunosorbent assays. Autophagy of myocardial cells was evaluated using transmission electron microscopy, and changes in signal pathway proteins related to autophagy were analyzed by Western blotting. GS combined with metoprolol improved heart function, reduced heart damage, and decreased serum levels of CK, CK-MB, LDH, and cTnT. The combination of GS and metoprolol decreased autophagy in myocardial cells by reducing the levels of autophagy-related proteins (LC3, p62, Beclin1, and Atg5) and increasing the ratios of p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR. GS enhanced the anti-heart failure effect of metoprolol. Its mechanism of action might be related to the inhibition of autophagy mediated by the activation of the PI3K/Akt/mTOR pathway.

LOW EJECTION FRACTION PATIENTS' RESPONSE TO HEART FAILURE REVERSAL THERAPY – A SINGLE CASE STUDY

In India, chronic heart failure (CHF) has increased significantly despite improved medicine therapy. The overall prognosis of CHF patients was found to be unsatisfactory due to a decreased ejection fraction or a low aerobic capacity in CHF patients, resulting in rising mortality and morbidity rates. Perhaps complementary and alternative medications can aid in the treatment of congestive heart failure as an adjuvant. Ayurveda is one approach which can be applied to the treatment. Several studies have demonstrated the efficacy of panchakarma therapy in treating a variety of illnesses, and it can be treated as Heart failure reversal therapy. Heart failure reversal therapy (HFRT) is a unique treatment intended to improve cardiorespiratory endurance in patients with CHF. This study quantifies the maximal aerobic capacity (MAC) of patients with CHF whose mortality and morbidity rates are rising. The objective of the present investigation was to assess the efficacy of HFRT as an adjuvant therapy for patients with CHF and a low ejection fraction. In the present case report, HF was treated for six months with conventional medicine. Then, only Ayurveda treatment was offered, along with lifestyle adjustment, after examining the cause and risk factors for heart disease. This case report thereby describes the beneficial role of Ayurveda in heart failure with poor ejection fraction (35%) in a 65-year-old male with comorbidities who has been treated in our institute for six months.

Short-term versus long-term metronomic adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: A propensity score-matched real-world study

BackgroundThis retrospective study aimed to determine the optimal metronomic chemotherapy duration (MTCD) as adjuvant therapy for patients with locally advanced nasopharyngeal carcinoma (LANPC). MethodsThis study involved LANPC patients treated with metronomic chemotherapy (MTC) using a 5-FU prodrug (S1, capecitabine, or tegafur) from May 2013 to September 2020. The optimal MTCD threshold was established using X-tile Bioinformatics software. The overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were compared between short-term and long-term groups using propensity score matching (PSM). ResultsA total of 546 patients were analyzed. MTCD was an independent prognostic factor for OS, PFS, and DMFS (all P < 0.05). Patients were categorized into long-term (>3 months) and short-term (≤3 months) MTCD groups. After a median follow-up of 48 months, significant differences were observed in 4-year OS (97.0 % vs. 87.1 %; P < 0.01), PFS (84.6 % vs. 70.9 %; P < 0.01), DMFS (87.3 % vs. 78.8 %; P < 0.01), and LRRFS (95.3 % vs. 87.4 %; P < 0.01) between the long-term and short-term groups. In the PSM-matched cohort of 196 patients per group, the long-term group demonstrated superior 4-year OS and LRRFS (97.3 % vs. 87.1 %, P < 0.01; 95.2 % vs. 90.0 %, P < 0.05). No significant differences in acute toxicities were observed between the groups (P > 0.05). ConclusionExtended MTC with a 5-FU prodrug (>3 months) may benefit NPC patients. Further prospective studies are needed to validate these findings.

Effect of Curcuma longa Extract as Adjuvant Therapy on IL-6 Serum Levels in Leprosy Type 1 Reaction Patients

Type 1 leprosy reaction / Reversal reaction (RR) is an inflammatory episode in existing leprosy lesions and aggravates the pain rate. Long-term therapy with steroids causes a variety of side effects, so an adjuvant therapy alternative is needed to alleviate steroid use. Curcuma longa rhizome extract has become an anti-inflammatory therapy choice in various previous inflammatory diseases. This study aims to determine the anti-inflammatory effect of Curcuma longa rhizome extract as an adjuvant therapy for reversal reaction patients by analyzing serum levels of IL-6 as a marker of inflammation. The pre and post-test randomized single-blinded controlled trial was conducted on two groups, namely control (RR patients with steroid therapy &amp; placebo) and treatment (steroid therapy &amp; Curcuma longa rhizome extract 1 gram/day). IL-6 serum levels were analyzed from sampling before and after the intervention for one month. The serum levels of IL-6 post-test in the control group were significantly higher than those of the pre-test. The treatment group showed lower serum levels of IL-6 post-test compared to pre-test, although there was no significant difference. Curcuma longa rhizome extract 1 gram/day for one month as adjuvant therapy for patients with type 1 leprosy reaction did not significantly reduce serum IL-6 levels.

Repurposing metformin as adjuvant therapy in patients with ulcerative colitis treated with mesalamine: A randomized controlled double-blinded study

BackgroundUlcerative colitis (UC) is a type of inflammatory bowel disease associated with persistent inflammation. Animal studies proved the efficacy of metformin in UC. AimTo investigate the potential role of metformin and its protective pathways in patients with UC. MethodsThis is a randomized, controlled, and double-blinded clinical trial that included 60 participants with mild to moderate UC and was divided randomly into two groups (n = 30). For 6 months, the mesalamine group received 1 g of mesalamine three times daily (t.i.d.). For six months, the metformin group received mesalamine 1 g t.i.d. and metformin 500 mg twice daily. A gastroenterologist evaluated patients at baseline and 6 months after starting the treatment in order to measure serum levels of zonulin, sphingosine 1 phosphate (S1P), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Biopsies from the colon were used to measure gene expression of zonula occuldin-1 (ZO-1), signal transducer and activator of factor-3 (STAT-3), and intracellular adhesion molecule-1 (ICAM-1). The numeric pain rating scale (NRS) and partial Mayo score were also assessed for each patient. ResultsWhen compared to the mesalamine group, the metformin group demonstrated a statistical decrease in serum IL-6, zonulin, TNF-α, SIP, gene expression of ICAM-1 and STAT-3, and a significant increase in colonic ZO-1 when compared to the mesalamine group. The metformin group also showed a significant decrease in NRS and partial Mayo score index in comparison with the mesalamine group. ConclusionMetformin may be a promising additional therapy for UC patients.Trial registration identifier: NCT05553704.

Potential efficacy and safety of Xiyanping injection as adjuvant therapy in treatment of suppurative acute tonsillitis: a meta-analysis, trial sequential analysis, and certainty of evidence.

Background: Antibiotic resistance has emerged as a global concern. Xiyanping injection (XYP), a traditional Chinese medicine injection, has been extensively utilized for the treatment of suppurative acute tonsillitis (SAT) in China, exhibiting clinical efficacy. Consequently, there is a need for further evaluation of the potential effectiveness and safety of this treatment. This meta-analysis consolidated data from multiple independent studies to assess the overall treatment efficacy of XYP as adjuvant therapy in patients with SAT. Methods: The search for randomized controlled trials (RCTs) encompassed databases from their inception to 1 April 2024, including the Cochrane Library, PubMed, Embase, SinoMed, CNKI, Wanfang, VIP, and CBM. Data extraction, methodological quality assessment, and meta-analysis were performed independently by two researchers. Review Manager 5.4 was used for data analysis. Various tools were employed for assessment, including forest plots to visualize results, funnel plots to detect publication bias, trial sequential analysis to estimate sample size, and GRADE to evaluate evidence quality. Results: A comprehensive analysis of 32 RCTs involving 4,265 cases was conducted. When compared to conventional treatments (CTs; β-lactams/clindamycin hydrochloride injection/ribavirin) alone, the combination of XYP with CTs demonstrated significant reductions in symptom duration. This included sore throat (MD = -21.08, 95% CI: -24.86 to -17.29, p < 0.00001), disappearance of tonsillar redness and swelling (mean difference [MD] = -20.28, 95% confidence interval [CI]: -30.05 to -10.52, p < 0.0001), tonsil purulent discharge (MD = -22.40, 95% CI: -28.04 to -16.75, p < 0.00001), and normalization of temperature (MD = -19.48, 95% CI: -22.49 to -16.47, p < 0.00001). Furthermore, patients receiving CTs combined with XYP exhibited lower levels of interleukin-6 (MD = -7.64, 95% CI: 8.41 to -6.87, p < 0.00001) and interleukin-8 (MD = -5.23, 95% CI: -5.60 to -4.86, p < 0.00001) than those receiving CTs alone. Additionally, the combination therapy significantly improved the recovery rate (relative risk [RR] = 1.55, 95% CI: 1.37 to 1.77, p < 0.00001), white blood cell count recovery rate (RR = 1.13, 95% CI: 1.04 to 1.23, p = 0.004), and disappearance rate of tonsillar redness and swelling (RR = 0.51, 95% CI: 1.14 to 1.38, p < 0.00001), with no significant increase in adverse events (RR = 0.47, 95% CI: 0.20 to 1.10, p = 0.08). Conclusion: The current systematic review and meta-analysis tentatively suggest that the combination of XYP and CTs yields superior clinical outcomes for patients with SAT compared to CTs alone, with a favorable safety profile. Nonetheless, these findings warrant further confirmation through more rigorous RCTs, given the notable heterogeneity and publication bias observed in the included studies. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=296118, identifier CRD42022296118.

Benefits of adjuvant treatment with the Pingxiao capsule in patients with early breast cancer: A single‑center retrospective cohort study.

Early breast cancer (EBC) is cancer that has not spread beyond the breast or the axillary lymph nodes. The present retrospective cohort study investigated the efficacy and safety of the Pingxiao capsule (PXC), which contains a formula of traditional Chinese herbs, as adjuvant therapy in patients with EBC in a single Chinese academic medical center. Patients with EBC who had received surgery and chemotherapy were analyzed and divided into the PXC and non-PXC groups. Disease-free survival (DFS) time, overall survival (OS) time, demographic characteristics and adverse events were examined. Kaplan-Meier survival curves were used to compare the differences in DFS and OS. A total of 371 participants with a median age of 54 years were included in this study. The median DFS time of all patients was 101 months. The overall DFS rate was 72.1% in the PXC group compared with 63.6% in the non-PXC group. For women with hormone receptor-negative tumors, the DFS rate in the PXC group was significantly higher than that in the non-PXC group, irrespective of node status. Adjuvant treatment with PXC for ≥3 months was associated with significantly longer median DFS time compared with that in the non-PXC group. In addition, the incidence of neutropenia rated to be grade 2 or higher was significantly lower in the PXC group compared with that in the control group, and a markedly, but non-significantly, lower prevalence of nausea was observed in PXC group (0 vs. 4.1%). In conclusion, PXC as an adjuvant therapy along with chemotherapy is associated with prolonged DFS times in patients with EBC when compared with chemotherapy alone. The therapeutic value of combined PXC and systemic chemotherapy should be further elucidated by rigorous prospective clinical trials.

Toripalimab (anti-PD-1) plus recombinant human endostatin as adjuvant therapy in patients with resected stage III melanoma: Interim analysis of an open-label phase II trial.

e21557 Background: Patients with completely resected stage III melanoma are under high risk of disease recurrence. Recurrence-free survival (RFS) remains unsatisfactory despite there is adjuvant anti-PD-1 monotherapy following surgery, with the 1-year RFS about 70% and 2-year RFS about 49% in our country. It's urgent to explore combined regimens with anti-PD-1 to further improve the RFS. Here we report the interim efficacy and safety results of toripalimab (a PD-1 inhibitor) plus recombinant human endostatin (an angiogenesis inhibitor) as combined adjuvant therapy for patients with resected stage III melanoma. Methods: This prospective single-center, single-arm, open-label phase II trial screened adult patients with stage III melanoma who had undergone complete tumor resection within the previous 13 weeks for eligibility. Toripalimab was administrated in intravenous drip to patients at 3 mg/kg every 2 weeks in a 4-week cycle (day 1 and day 15 of each cycle), for up to 13 cycles or until disease recurrence, unacceptable toxicity or decease. Recombinant human endostatin was administrated in a continuous intravenous infusion at a dose of 210 mg from day 1 to day 3 for each 4-week cycle, for up to 6 cycles or until disease recurrence, unacceptable toxicity or decease. The primary endpoints were the 1-year and 2-year RFS. Results: By the data cut-off on Jan 25, 2024, 43 eligible patients with resected stage III melanoma between October 2021 and December 2023 were enrolled. In ITT population (n = 43), patients' median age was 56 (IQR 52~69) years. There were 25 (58%) male and 18 (42%) female; 27 (63%) with acral melanoma and 16 (37%) with cutaneous melanoma. With a median follow-up of 14 months, the 1-year and 2-year RFS rates were 83% and 71%, respectively. For security, 33 (77%) patients experienced at least one adverse event (AE), including 27 grade 1-2 AEs and 6 grade 3~4 AEs. One patient discontinued the combined therapy due to immunotherapy-associated myocarditis. Conclusions: Toripalimab in combination with recombinant human endostatin as adjuvant therapy could further improve disease-free survival in Chinese patients with completely resected stage III melanoma, with a manageable toxicity profile. Clinical trial information: 05907512 .

The efficacy and safety study of thymosin α1 combined with PD-1 antibodies as adjuvant therapy in patients with hepatocellular carcinoma with high-risk recurrence factors after radical resection.

e16226 Background: Anti-PD-1 immunotherapy has revolutionized unresectable hepatocellular carcinoma (HCC) treatment. The efficacy of postoperative adjuvant therapy (PAT) using anti-PD-1 in treating HCC is currently the subject of extensive research. This study explored the efficacy and safety of anti-PD-1 antibodies combined with thymosin alpha-1 (Tα1) for patients with HCC and high-risk recurrent factors (HRRFs) post-hepatectomy. Methods: Data from 273 patients with HCC and HRRFs who underwent hepatectomy at Tongji Hospital (January 2019 to July 2022) were prospectively collected. Patients were nonrandomly divided into Tα1+ anti-PD-1 antibodies (65, 23.8%), anti-PD-1 antibodies (84, 30.8%), and control (no adjuvant therapy, 124, 45.4%) groups based on finances and willingness. After propensity score matching (PSM), recurrence-free survival (RFS) and overall survival (OS) were compared. Cox regression analysis identified the RFS- and OS-related prognostic factors, followed by subgroup analysis. Results: After PSM, 65 patients were matched. The anti-PD-1 antibodies + Tα1 group exhibited longer RFS than the anti-PD-1 antibodies (P = 0.014) and control (P &lt; 0.0001) groups. The anti-PD-1 antibodies group had longer RFS than the control group (P &lt; 0.0001). The anti-PD-1 antibodies + Tα1 (P = 0.00049) and anti-PD-1 antibodies groups (P = 0.0041) demonstrated longer OS than the control group. The 1- and 2-year RFS rates in the Tα1 + anti-PD-1 antibodies, anti-PD-1 antibodies, and control groups were 98.4%, 86.2%, and 49.2% (P &lt; 0.001), and 80.2%, 65.8%, and 24.6% (P &lt; 0.001), respectively. The corresponding 1-, 2-, and 3-year OS rates were 100.0%, 100.0%, and 84.6% (P &lt; 0.001), 98.0%, 91.4%, and 69.0% (P &lt; 0.001), and 91.3%, 86.8%, and 57.4% (P &lt; 0.001), respectively. Multivariable analyses suggested that the Tα1 + anti-PD-1 antibodies treatment improved the RFS and OS more than the non-anti-PD-1 antibodies + Tα1 treatment (hazard ratio (HR): 0.174, 95% confidence intervals (CI): 0.089–0.340, P &lt; 0.001 and HR: 0.240, 95% CI: 0.084–0.683, P = 0.008, respectively). Subgroup analysis demonstrated significant RFS and OS benefits for patients with HCC and vascular invasion treated with Tα1 + anti-PD-1 antibodies. Grade 1 and 2 toxicities included rash/pruritus (21.5%), diarrhea (18.5%), and reactive cutaneous capillary endothelial proliferation (RCCEP)(15.4%). Grade 3 toxicities included RCCEP (1.5%), diarrhea (1.5%), rash/pruritus (0.8%), edema (0.8%), hepatitis (0.8%), nausea/vomiting (0.8%), and hypothyroidism (0.8%). No grade 4/5 toxicities or severe adverse events were detected. Conclusions: Combining anti-PD-1 antibodies with Tα1 as adjuvant therapy is safe, improving postoperative prognosis in patients with HCC and HRRFs after hepatectomy, proving more effective than anti-PD-1 antibodies alone.

Efficacy and safety of donafenib as adjuvant therapy for patients with hepatocellular carcinoma undergoing curative resection: A retrospective, multicenter cohort study.

e16234 Background: A growing incidence of hepatocellular carcinoma and its high risk of recurrence after curative-intent treatment underscore the need for effective adjuvant treatment options. This study aimed to assess the efficacy of adjuvant donafenib in patients with hepatocellular carcinoma (HCC) following radical resection. Methods: This multicenter, real-world study retrospectively gathered clinical data of 82 patients who had undergone radical resection of HCC and received adjuvant therapy with donafenib. The primary endpoint was recurrence-free survival (RFS). The secondary endpoints included overall survival (OS) and safety. Kaplan-Meier analysis was performed to evaluate RFS and OS, while the Cox proportional-hazards model was used to estimate risk factors for tumor recurrence and death. Results: A total of 82 patients with HCC who received donafenib following surgical resection were included in the study, of which were classified as high risk for tumor recurrence (with multiple or large tumor, microvascular invasion, poor tumor differentiation). The median duration of donafenib adjuvant therapy was 10.6 months (range: 0.2–26.1 months). All patients completed follow-up as required, with a median follow-up time of 19.4 months (range: 2.8–57.6 months). During the follow-up period, a totally postoperative recurrence rate was 15.9% (13/82). 1-year recurrence rate and 2-year recurrence rate were 7.3% (6/82) and 12.2% (10/82), and 1-year survival rate and 2-year survival rate were 95.1% (78/82) and 93.9% (77/82). Kaplan-Meier analysis demonstrated that patients with higher preoperative AFP level (AFP &gt; 400ng/mL), higher preoperative PIVKA-II level (PIVKA-II &gt; 40mAU/mL), or poor tumor differentiation (Edmondson stage III-IV) exhibited higher rate of tumor recurrence after operation (all p value &lt; 0.05). Multivariate analysis indicated that preoperative AFP level was an independent risk factor for tumor recurrence in patients with donafenib treatment. Treatment-related adverse events (TRAEs) occurred in 67.1% (55/82) of patients, of which the most frequent were hand-foot syndrome (25.6%, 21/82), diarrhea (20.7%, 17/82), and fatigue (17.1%, 14/82). Only 8.5% (7/82) of patients had a grade ≥3 TRAEs, with the most common being hand-foot syndrome (2.4%, 2/82) and hypertension (2.4%, 2/82). No treatment-related deaths were reported. Conclusions: This study represents the largest multicenter investigation of adjuvant therapy with donafenib to date, and the findings indicate that donafenib has the potential to be an effective treatment option for preventing postoperative recurrence in HCC. Furthermore, the preoperative AFP ≤400ng/mL can serve as an effective biomarker for postoperative administration of donafenib in HCC patients.

Tislelizumab plus sitravatinib as adjuvant therapy for patients with hepatocellular carcinoma at high risk of recurrence after surgical resection: Preliminary analysis of a multi-center, non-randomized, open-label phase 2 study.

e16239 Background: Adjuvant therapy has the potential to prevent or delay recurrence after curative-intent hepatectomy for hepatocellular carcinoma (HCC) patients. IMbrave 050 trial demonstrated improved recurrence-free survival (RFS) for HCC patients at high risk of recurrence when treated with atezolizumab plus bevacizumab, underscoring the promising potential of checkpoint inhibitor-based combination therapy as a strategy in the adjuvant setting. The aim of this study was to evaluate the efficacy and safety of tislelizumab (a PD-1 inhibitor) plus sitravatinib (a selective tyrosine kinase inhibitor) as adjuvant therapy in HCC patients at high risk of recurrence after curative-intent hepatectomy. Here, we reported the preliminary analysis results. Methods: HCC patients confirmed by histopathology or cytology, who had undergone a curative resection and with one or more of the high-risk factors for recurrence, including: a solitary tumor&gt;5 cm, a solitary tumor&gt;2cm and ≤5cm with microvascular invasion, or 2~3 lesions, were eligible. Enrolled patients received tislelizumab (200mg, IV, Q3W) and sitravatinib (100mg, PO, QD), with a maximum treatment duration of one year. The primary endpoint was 2-year RFS rate. Secondary endpoints include RFS, time to recurrence, overall survival (OS), 1-year RFS rate, 1-year and 2-year OS rate, and safety. Results: A total of 22 patients were enrolled, with hepatitis B being the most common (86.4%) etiology, and 36.4% with microvascular invasion. Most patients were at BCLC stage A (86.4%), while stage 0 and stage B accounted for 4.5 and 9.1%, respectively. Till the data cut-off date on Nov. 30th, 2023, the median follow-up duration was 6.0 months (range 0.7-16.2); 2 patients relapsed and 1 patient died. The 1-year RFS rate was 81.3% and the longest RFS (censored) was over 12.5 months. Safety profile indicated that 21 patients (95.5%) experienced treatment-related adverse events (TRAEs), and 8 (36.4%) experienced grade ≥3 TRAEs. Most common (≥10%) grade ≥3 TRAEs were hypertension (13.6%) and palmar-plantar erythrodysesthesia (13.6%). Any grade immune-related adverse events (irAEs) were observed in 12 patients (54.5%) and 3 (13.6%) experienced grade ≥ 3 irAEs. AE leading to tislelizumab delay was observed in 2 patients (9.1%) and sitravatinb delay in 16 patients (72.7%). Dose reduction of sitravatinib occurred in 81.8% of patients due to AE. One patient died due to treatment-related pulmonary infection and biliary fistula. Conclusions: For patients with HCC at high risk of recurrence after curative-intent resection, tislelizumab plus sitravatinib showed preliminarily positive signal in controlling recurrence and had managable safety profile as adjuvant therapy. Further follow-up is needed to validate these findings with more mature data. Clinical trial information: NCT05407519 .

Tislelizumab combined with gemcitabine and cisplatin (GC) as adjuvant therapy in patients with high-risk upper urothelial carcinoma (UTUC) after surgery: A 2-year follow-up, real-world study.

Tislelizumab combined with gemcitabine and cisplatin (GC) as adjuvant therapy in patients with high-risk upper urothelial carcinoma (UTUC) after surgery: A 2-year follow-up, real-world study.

Evaluation of adjuvant role of topical cyclosporine 1% in acute Stevens-Johnson syndrome: a randomised control trial

PurposeTo evaluate the role of topical cyclosporine A 1% (CsA) as an adjuvant therapy in patients with acute Stevens-Johnson syndrome (SJS).MethodsThis is a randomised controlled trial in which 44 patients...