Postoperative Adjuvant Therapy Research Articles

PECULIARITIES OF ORAL CANCERS IN POLAND - A REVIEW OF THE LITERATURE

Oral cancers are seen frequently. By 2040, according to the Global Cancer Observatory (GCO), their number will increase by around 40%. Exposure to alcohol, tobacco smoke, human papillomavirus (HPV) or a diet low in fibre is often part of everyday life, which is a risk factor for developing oral cancer. The most common of these is oral squamous cell carcinoma. The most common treatment is primary surgical resection with or without postoperative adjuvant therapy. In addition, various combination therapies including chemotherapy with radiotherapy or immunotherapy are used. Oral cancers are usually detected early but delayed treatment can lead to a bad prognosis and require facial reconstructive surgery. Aim: The aim of the publication was to bring together the latest information on oral cancer in Poland. We wanted to present the division, the most commonly observed symptoms and the proposed treatment. Methods: Analysis of information on oral cancer using PubMed sources, including classification of cancer types, symptoms and possible treatments. Conclusions: Oral cancers are a common problem for the population of Poland. Their incidence is likely to increase over the next decade. The environment, lifestyle and diet have a key influence on their formation. The most common treatment is their resection combined with radiation therapy, chemotherapy or immunotherapy.

Update on the management of ductal carcinoma in situ of the breast: current approach and future perspectives.

The standard treatment for ductal carcinoma in situ became well established through the results of several valuable clinical trials, and its therapeutic benefits have now come to be taken for granted. Ductal carcinoma in situ has an extremely good prognosis with the current treatment approach, with a 10-year breast cancer-specific survival rate of 97-98%. According to one retrospective cohort study, the breast cancer-specific survival rate of patients with low-grade ductal carcinoma in situ does not differ significantly between patients undergoing and not undergoing surgery. Some patients with ductal carcinoma in situ are not at a risk of progression to invasive cancer, but the predictors of such progression have not yet been clearly identified. Therefore, the same therapeutic strategies have been used to treat ductal carcinoma in situ and under the assumption that they have risks of invasive breast cancer, and a well-balanced risk/benefit ratio in respect of treatment has not yet been achieved. Based on the results of several recent clinical trials aimed at ensuring provision of a well-balanced treatment for patients with ductal carcinoma in situ which carries a good prognosis, de-escalation of postoperative adjuvant therapy has now begun. Currently, not only is the optimization of postoperative adjuvant therapy accelerating, but also clinical trials to de-escalate basic surgical treatments are under way. There is a possibility of achieving individualized treatment for patients with ductal carcinoma in situ of the breast with reduced treatment intervention. In this review, we present an overview of the current treatment approaches and potential future management strategies for ductal carcinoma in situ of the breast.

Vulvar Paget's disease: a population-based cancer registry descriptive study.

Although vulvar Paget's Disease (VPD) is a rare skin cancer associated with an excellent prognosis, high recurrence rates are associated with impaired quality of life. Our objective was to investigate the epidemiological and clinical features of VPD diagnosed in a French administrative area (Franche Comté). This retrospective study investigated clinical, histologic, therapeutic and follow-up data of patients with VPD diagnosed between 1981 and 2021, including data from the Doubs cancer registry. Among the 21 patients included (19 intra-epithelial and 2 invasive VPD), the median time to diagnosis was 24 months [0-110 months], with a median age of 72 years [38-88 years]. An associated cancer was present in 6 patients (29%). At 5 years of follow-up, the recurrence rate was 26%, but then increased to 42% after a median follow-up of 145 months [31-503 months]. Among the 14 patients first surgically treated, incomplete resection (positive margins) was observed in all patients (100%), associated with a postoperative recurrence rate of 86% which was much higher than the rate observed in patients first topically treated (20%). Postoperative adjuvant therapy (surgical revision, laser, imiquimod) significantly increased the recurrence-free survival (p < 0.001). Postoperative recurrence of VPD is frequent, mainly after 5 years, proving the importance of prolonged follow-up. Recurrence-free survival was significantly higher after postoperative adjuvant treatment.

236. THE ROLE OF ADJUVANT THERAPY FOLLOWING NEOADJUVANT CHEMORADIOTHERAPY AND ESOPHAGECTOMY IN ESOPHAGEAL CANCER

Abstract Background The objective of this study was to assess the role of adjuvant therapy following neoadjuvant chemoradiotherapy and esophagectomy in esophageal squamous cell carcinoma (ESCC). Methods We conducted a retrospective analysis involving 506 ESCC patients who underwent trimodal therapy. The clinical significance of adjuvant therapy on overall survival and disease-free survival was evaluated using Kaplan–Meier curves with log-rank tests, the Cox regression model, and a forest plot displaying hazard ratios (HR) with 95% confidence intervals. Results Among the 506 patients who had clinically positive lymph nodes and no metastasis after neoadjuvant chemoradiotherapy and esophagectomy, those who received adjuvant therapy exhibited shorter post-resection overall survival (OS) and disease-free survival (DFS), with a statistically significant difference between the two groups (Log-Rank, OS: P = 0.002; DFS: P &amp;lt; 0.001). Adjuvant therapy was not identified as an independent prognostic factor for OS (HR: 1.249; 95% CI: 0.869-1.796; P = 0.230), but it was a significantly unfavorable independent prognostic factor for DFS (HR: 1.868; 95% CI: 0.349-2.586; P &amp;lt; 0.001). Conclusion Adjuvant therapy is associated with poorer overall survival (OS) and disease-free survival (DFS) outcomes in ESCC patients with ypTNM stage I and II on final pathology following neoadjuvant chemoradiotherapy and esophagectomy. However, there was no significant difference observed in patients with ypTNM stage III or IV. Therefore, it is not recommended to undergo postoperative adjuvant therapy for patients with ypTNM stage I and II ESCC. However, for patients with ypTNM stage III and IV ESCC, further research is needed to explore adjuvant treatment strategies.

Impact of Lymph Node Dissection for Patients With Clinically Node-Negative Intrahepatic Cholangiocarcinoma: A Multicenter Cohort Study.

Lymph node status is a prominent prognostic factor for intrahepatic cholangiocarcinoma (ICC). However, the prognostic value of performing lymph node dissection (LND) in patients with clinical node-negative ICC remains controversial. The aim of this study was to evaluate the clinical value of LND on long-term outcomes in this subgroup of patients. We retrospectively analyzed patients who underwent radical liver resection for clinically node-negative ICC from three tertiary hepatobiliary centers. The propensity score matching analysis at 1:1 ratio based on clinicopathological data was conducted between patients with and without LND. Recurrence-free survival (RFS) and overall survival (OS) were compared in the matched cohort. Among 303 patients who underwent radical liver resection for ICC, 48 patients with clinically positive nodes were excluded, and a total of 159 clinically node-negative ICC patients were finally eligible for the study, with 102 in the LND group and 57 in the non-LND group. After propensity score matching, two well-balanced groups of 51 patients each were analyzed. No significant difference of median RFS (12.0 vs. 10.0 months, P = 0.37) and median OS (22.0 vs. 26.0 months, P = 0.47) was observed between the LND and non-LND group. Also, LND was not identified as one of the independent risks for survival. Among 51 patients who received LND, 11 patients were with positive lymph nodes (lymph node metastasis (LNM) (+)) and presented significantly worse outcomes than those with LND (-). On the other hand, postoperative adjuvant therapy was the independent risk factor for both RFS (hazard ratio (HR): 0.623, 95% confidence interval (CI): 0.393 - 0.987, P = 0.044) and OS (HR: 0.585, 95% CI: 0.359 - 0.952, P = 0.031). Furthermore, postoperative adjuvant therapy was associated with prolonged survivals of non-LND patients (P = 0.02 for RFS and P = 0.03 for OS). Based on the data, we found that LND did not significantly improve the prognosis of patients with clinically node-negative ICC. Postoperative adjuvant therapy was associated with prolonged survival of ICC patients, especially in non-LND individuals.

The benefit of dupilumab as a postoperative short-term adjuvant therapy for chronic rhinosinusitis with nasal polyps: A preliminary study.

Recent evidence recommends the use of biologics in patients with severe uncontrolled type 2 chronic rhinosinusitis with nasal polyp (CRSwNP) owing to its propensity for recurrence after functional endoscopic sinus surgery (FESS). Among the type 2 biologics used for the treatment of nasal polyps, dupilumab (Dupi, anti-IL-4) exhibited superior efficacy and safety in indirect comparison studies. This study aimed to evaluate the objective and subjective outcomes of patients with CRSwNP treated with and without adjuvant Dupi therapy after FESS. Adult patients with type 2 CRSwNP who underwent FESS with adjuvant Dupi after surgery were enrolled. A matched control group without adjuvant Dupi therapy were recruited during the same period. All patients underwent nasal endoscopy and completed the sinonasal outcome test-22 questionnaire evaluations at baseline and 3 months after surgery. A total of 10 patients who received postoperative adjuvant therapy with Dupi and 20 patients who underwent surgery only were included. Patients with add-on Dupi therapy had significantly higher eosinophil cationic protein levels in the serum, eosinophil counts in peripheral blood, prevalence of asthma, and nasal polyp score at baseline. Both treatments were effective in reducing the patient's symptoms by SNOT-22 at 3 months postoperatively. However, patients with adjuvant Dupi therapy exhibited significantly better endoscopic scores than those with surgery only (p = .022). Surgery plays an important role in treating patients with CRSwNP, and adjuvant Dupi use may facilitate objective mucosal recovery postoperatively. 4.

A prospective single arm cohort study: An analysis of the effectiveness of surgical treatment of locally advanced breast cancer

BackgroundBreast cancer stands as a globally significant contributor to both incidence rates and mortality among women. Approximately 10–15 % of women will face a diagnosis of an advanced yet potentially treatable stage of the disease. When individuals diagnosed with locally advanced breast cancer (LABC) exhibit resistance to preoperative chemotherapy and experience tumor progression, they unfortunately forfeit the opportunity for surgical intervention, thereby diminishing the prospects for a radical cure. MethodWe conducted a prospective, single-arm cohort study aimed at evaluating the feasibility of locally modified radical resection for LABC with skin invasion. The primary endpoints encompassed overall survival (OS) and disease-free survival (DFS), whereas the secondary endpoint focused on the quality of life (QoL) among breast cancer patients. ResultsBetween March 2018 and December 2022, a total of 38 eligible patients were enrolled in this study. The Kaplan-Meier estimates for 1-year, 3-year, and 5-year DFS among all patients were 69.8 %, 53.3 %, and 37.5 %, respectively. Correspondingly, the OS rates were 100.0 %, 85.6 %, and 68.0 %. Both univariate and multivariate analyses revealed that patients with a history of neoadjuvant chemotherapy who exhibited stable or progressive disease had inferior DFS outcomes. Notably, patients demonstrated clinically meaningful and statistically significant enhancements in functional status and overall QoL. However, no notable improvement was observed in specific symptom domains. ConclusionPatients with locally advanced breast cancer, specifically those presenting with T4 tumors, who undergo surgical intervention followed by postoperative adjuvant therapy, can attain favorable prognostic outcomes and experience an enhanced quality of life.

Pathological complete response after conversion therapy in unresectable hepatocellular carcinoma: a retrospective study

BackgroundHepatocellular carcinoma is a highly lethal tumor worldwide, and China has a correspondingly high incidence and mortality rate. For patients with unresectable hepatocellular carcinoma, the prognosis is often poor. The objective of this retrospective study was to investigate the effects of conversion therapies on these patients.MethodsThe study included patients between the ages of 18 and 75 who were initially diagnosed with unresectable hepatocellular carcinoma and received conversion therapy. After completing surgery, the patients underwent pathological diagnosis, which showed complete necrosis. The study was conducted retrospectively at the First Affiliated Hospital, Zhejiang University School of Medicine, from January 2019 to December 2021. The main objectives of the study were to evaluate the overall survival and recurrence-free survival.ResultsA total of 60 patients who met the inclusion criteria were enrolled. The median age of the patients was 56.6 ± 9.5 years, and 85% of them were male. The one-year overall survival rate (OS) was 98.3%, and the three-year OS was 95.6%. The one-year recurrence-free survival rate (RFS) was 81.1%, and the three-year RFS was 71.4%. In subgroup analysis, there was no statistically significant difference in RFS between patients with BCLC stages 0-A and BCLC stages B-C (p = 0.296). Additionally, there was no statistically significant difference in RFS between patients who received postoperative new adjuvant therapy and those who did not (p = 0.324).ConclusionsConversion therapy followed by surgical resection could be a promising treatment for patients with initially unresectable hepatocellular carcinoma, and the prognosis is good with a pathological complete response.

Whole-Exome Sequencing Identifies Germline BLM Mutation in Ovarian Hepatoid Adenocarcinoma with Favorable Response to Niraparib and Anlotinib Combination Therapy-A Case Report and Literature Review.

Hepatoid adenocarcinoma of the ovary represents a rare and malignant extrahepatic tumor that shares morphological and immunophenotypic similarities with hepatocellular carcinoma. Due to the ambiguous histomorphology and aggressive behavior, the diagnosis and management of hepatoid adenocarcinoma of the ovary present unique challenges. Here, we present a 67-year-old woman with massive ascites and disseminated peritoneal implants at initial diagnosis. She was treated with six cycles of neoadjuvant therapy (albumin-bound paclitaxel + nedaplatin + bevacizumab) and a debulking surgery, followed by eight cycles of postoperative adjuvant therapy (albumin-bound paclitaxel + carboplatin + bevacizumab). Elaborate pathology workup found significant involvement of angiogenesis in the tumor and confirmed the diagnosis via immunohistochemistry. Further molecular characterization of the tumor by whole-exome sequencing (WES) revealed a novel heterozygous germline mutation (NM_000057.2, c.1290_1291delinsATCAGGCCTCCATAG, p.Y430fs1) in gene BLM, likely pathogenic, suggesting a potential candidate for Poly (ADP-ribose) polymerase (PARP) inhibitors. For the maintenance therapy, she received a combination of the PARP inhibitor niraparib and the antiangiogenic anlotinib. As of now, the patient has achieved a partial response, with no apparent evidence of disease progression observed nearly 30 months. Our study sheds light on the WES-based profiling in rare cancers to screen for any treatable targets with otherwise no standard therapeutic options. The promising results with the niraparib-anlotinib combination suggest its potential as a maintenance therapy option for hepatoid adenocarcinoma of the ovary, which warrants validation in future larger cohort.

Treatment, Prognostic Markers, and Survival in Thymic Neuroendocrine Tumors, with Special Reference to Temozolomide-Based Chemotherapy.

Thymic neuroendocrine tumors (Th-NETs) are rare and aggressive, with a scarcity of research on predicting patient prognosis. Our study aimed to assess the impact of prognostic markers and temozolomide (TMZ)-based chemotherapy on survival in Th-NETs. We retrospectively reviewed the medical records of patients diagnosed with Th-NETs between 2013 and 2023 at our institution. We collected clinicopathological data, including tumor pathological grading, staging, serum concentrations of neuron-specific enolase (NSE) and pro-gastrin-releasing peptide, levels of inflammatory factors, and expression of oxygen 6-methylguanine-DNA methyltransferase (MGMT). Treatment details (such as surgery and chemotherapy) and survival outcomes were also documented. A total of 32 patients were included in our study after excluding those without complete available information. The median progression-free survival (PFS) was 12.5 months (95%CI, 8-16 months) for 19 patients who received TMZ-based chemotherapy. Twenty-one patients underwent surgery as the primary treatment, demonstrating a median disease-free survival (DFS) of 51.0 months. The inflammatory factor neutrophil-to-lymphocyte ratio (NLR) was an independent prognostic indicator of DFS in postoperative patients and PFS in TMZ-treated patients. The overall 3-, 5-, and 10-year survival rates were 86.6%, 69.5%, and 33.8%, respectively. Ki67 level exceeding 10% (p = 0.048) and absence of surgical resection (p = 0.003) were significantly associated with worse overall survival (OS). Surgical treatment was currently the primary method for treating Th-NETs, and postoperative adjuvant therapy was an essential consideration for specific patient cohorts. Despite widespread positive MGMT expression, TMZ-based chemotherapy showed promise. Some potential prognostic biomarkers such as NLR and NSE need more attention.

Application of 21-gene recurrence risk score in patients with breast cancer

Objective: To investigate the relationship between 21-gene recurrence risk score (21-Gene RS) and the prognosis and clinicopathological features of hormone receptor (HR) positive, HER2-negative early breast cancer patients who did not receive neoadjuvant therapy. Methods: A total of 469 patients with HR positive and HER2-negative early breast cancer who received surgical treatment in the First Affiliated Hospital, Zhejiang University School of Medicine from January 2014 to October 2017 were selected. Their clinicopathological data were retrospectively analyzed. Tumor tissue samples were collected from patients, and the expression of 21-gene was detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The 21-Gene RS was calculated according to the Trial Assigning Individualized Options for Treatment (TAILORx) RS grouping and National Surgical Adjuvant Breast and Bowel Project B-20 (NSABP B-20) RS grouping principles. Patients were divided into low (21-Gene RS<11 or 21-Gene RS<18), intermediate (11≤21-Gene RS<26 or 18≤21-Gene RS<31) and high (21-Gene RS≥26 or 21-Gene RS≥31) risk groups, and the clinicopathological features and prognostic differences of patients in different risk groups were compared. Statistical data were compared by chi-square test. Survival analysis was performed using Kaplan-Meier curve analysis and the differences between groups were compared using Log-rank test. Multivariate analysis was conducted by COX regression analysis. Results: Based on TAILORx RS grouping, the proportions of low-risk, intermediate-risk and high-risk groups among the 469 patients were 18.8% (88/469), 48.2% (226/469) and 33.0% (155/469), respectively. Based on NSABP B-20 RS grouping, the proportion of low-risk, intermediate-risk and high-risk groups were 43.1% (202/469), 37.5% (176/469) and 19.4% (91/469), respectively. The association of 21-Gene RS with histological grading, luminal typing, Ki-67 expression, and chemotherapy and treatment modalities were statistically significant (P<0.05) regardless of TAILORx RS grouping or NSABP B-20 RS grouping. Kaplan-Meier survival curve suggested poor prognosis in high-risk group (P<0.05, Log-rank test). Multivariate COX regression analysis showed that surgical method and 21-Gene RS were risk factors affecting the prognosis of patients. Conclusions: 21-Gene RS is significantly associated with the prognosis of patients with HR-positive, HER2-negative, early-stage breast cancer not receiving neoadjuvant therapy, as well as with their clinicopathological characteristics such as patients' histologic grade, luminal typing, Ki-67 expression, and whether or not they are treated with chemotherapy or other treatment modalities.The 21-Gene RS threshold of 11 and 26 or 18 and 31 can be used to grade the prognosis in Chinese patients with early-stage breast cancer. More researches are needed to guide the selection of postoperative adjuvant therapy for patients with HR-positive and HER2-negative early-stage breast cancer.

Impact of frozen section on long-term outcomes in robot-assisted laparoscopic prostatectomy.

To compare 1-year functional and 5-year oncological outcomes of men undergoing robot-assisted laparoscopic prostatectomy (RALP) with neurovascular structure-adjacent frozen-section examination (NeuroSAFE) with those in men undergoing RALP without NeuroSAFE (standard of care [SOC]). Men undergoing RALP in our centre between 1 January 2009 and 30 June 2018 were enrolled from a prospectively maintained database. Patients were excluded if they had undergone preoperative therapy or postoperative adjuvant therapy or were enrolled in clinical trials. Patients were grouped based on use of NeuroSAFE. Follow-up was censored at 5 years. The primary outcome was difference in time to biochemical recurrence (BCR) on multivariable analysis, defined as prostate-specific antigen (PSA) >0.2 ng/L on two consecutive measurements. Secondary outcomes were difference in 1-year erectile dysfunction and incontinence. In the enrolment period, 1199 consecutive men underwent RALP, of whom 1140 were eligible, including 317 with NeuroSAFE and 823 with SOC. The median PSA follow-up was 60 months in both groups. Rates of 5-year BCR were similar on Kaplan-Meier survival curve analysis (11% vs 11%; P = 0.9), as was time to BCR on multivariable Cox proportional hazards modelling (hazard ratio 1.2; P = 0.6). Compared with the SOC group at 1 year, the NeuroSAFE group had similar unadjusted rates of incontinence (5.1% vs 7.7%) and lower unadjusted impotence (57% vs 80%). On multivariable analysis, NeuroSAFE patients had equivalent risk of incontinence (odds ratio [OR] 0.59, 95% CI 0.17-1.6; P = 0.4) but significantly reduced risk of erectile dysfunction (OR 0.37, 95% CI 0.22-0.60; P < 0.001). For men undergoing RALP, compared with SOC, NeuroSAFE patients had equivalent time to BCR and risk of 1-year incontinence, and significantly lower risk of 1-year erectile dysfunction.

Prognostic factors and impact of bone invasion in T1/2 size (

The aim of this study was to characterize the clinicopathological features and prognostic factors of T1/2 size (<4 cm) gingival squamous cell carcinoma (SCC) and to verify the impact of bone invasion. This was a single-centre, retrospective cohort study involving 206 patients with gingival SCC (maxilla or mandible), treated between 2000 and 2020. The patients were divided into three subgroups based on tumour size and bone invasion. The 5-year overall survival (OS) and disease-free survival (DFS) were 80.6% and 67.6%, respectively. Histological differentiation, advanced T stage, positive resection margin, bone invasion, and postoperative adjuvant therapy were associated with a poor prognosis (P < 0.05). Multivariate Cox analysis indicated that only histological differentiation (hazard ratio (HR) 2.68, P = 0.007) and bone invasion (HR 2.08, P = 0.036) were significantly associated with DFS. Bone invasion was observed in 145 (70.4%) patients, of whom 43 (20.9%) had a T1/2 size tumour. The subgroup with bone invasion and T1/2 size showed significantly worse OS and DFS when compared to the subgroup without bone invasion and similar or worse survival when compared to the subgroup with bone invasion and T3/T4 size. Histological differentiation and bone invasion were poor prognostic factors for gingival SCC, even in cases with small-sized tumours. For suspected bone invasion in small-sized tumours, an adequate bone margin is necessary and postoperative adjunctive therapy needs to be considered.

Neoadjuvant chemoimmunotherapy in resectable locally advanced oral squamous cell carcinoma: a single-center retrospective cohort study.

Surgery and postoperative adjuvant therapy is the standard treatment for locally advanced resectable oral squamous cell carcinoma (OSCC), while neoadjuvant chemoimmunotherapy (NACI) is believed to lead better outcomes. This study aims to investigate the effectiveness of NACI regimens in treating locally advanced resectable OSCC. Patients diagnosed with locally advanced resectable OSCC who received NACI and non-NACI were reviewed between December 2020 and June 2022 in our single center. The pathologic response was evaluated to the efficacy of NACI treatment. Adverse events apparently related to NACI treatment were graded by Common Terminology Criteria for Adverse Events, version 5.0. Disease-free survival (DFS) and overall survival (OS) rate were assessed. Our analysis involved 104 patients who received NACI. Notably, the pathological complete response (PCR) rate was 47.1%, and the major pathological response (MPR) rate was 65.4%. The top three grade 1-2 treatment-related adverse events (TRAEs) were alopecia (104; 100%), anemia (81; 77.9%) and pruritus (62; 59.6%). Importantly, patients achieving MPR exhibited higher programmed cell death-ligand 1 (PD-L1) combined positive score (CPS). The diagnostic value of CPS as a biomarker for NACI efficacy was enhanced when combined total cholesterol level. The 3-year estimated DFS rates were 89.0% in the NACI cohort compared to 60.8% in the non-NACI cohort, while the 3-year estimated OS rates were 91.3% versus 64.0%, respectively. The NACI treatment showed safe and encouragingly efficacious for locally advanced resectable OSCC patients. The high response rates and favorable prognosis suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings.

In situ engineered magnesium alloy implant for preventing postsurgical tumor recurrence

Invasive tumors are difficult to be completely resected in clinical surgery due to the lack of clear resection margins, which greatly increases the risk of postoperative recurrence. However, chemotherapy and radiotherapy as the traditional means of postoperative adjuvant therapy, are limited in postoperative applications, such as multi-drug resistance and low sensitivity, etc. Therefore, an engineered magnesium alloy rod is designed as a postoperative implant to completely remove postoperative residual tumor tissue and inhibit tumor recurrence by gas and mild magnetic hyperthermia therapy (MMHT). As a reactive metal, magnesium alloy responds to the acidic tumor microenvironment by continuously generating hydrogen. The in-situ generation of hydrogen not only protects the surrounding normal tissue, but also enables the magnesium alloy to achieve MMHT under low-intensity alternating magnetic field (AMF). Furthermore, the numerous reactive oxygen species (ROS) produced by heat stress will combine with nitric oxide (NO) generated in situ, to produce more toxic reactive nitrogen species (RNS) storm. In summary, engineered magnesium alloy can completely remove residual tumor tissue and inhibit tumor recurrence by MMHT and RNS storm under low-intensity AMF, and the biodegradability of magnesium alloy makes great potential for clinical application.

Injectable nano-in situ-thermosensitive-hydrogels based on halofuginone and silver for postoperative treatment against triple-negative breast cancer

Postoperative distant metastasis and high recurrence rate causes a dilemma in treating triple-negative breast cancer (TNBC) owing to its unforeseeable invasion into various organs or tissues. The wealth of nutrition provided by vascular may facilitate the proliferation and angiogenesis of cancer cells, which further enhance the rates of postoperative metastasis and recurrence. Chemotherapy, as a systemic postoperative adjuvant therapy, is generally applied to diminish recurrence and metastasis of TNBC. Herein, an halofuginone-silver nano thermosensitive hydrogel (HTPM&AgNPs-gel) was prepared via a physical swelling method. The in vitro anticancer efficacy of HTPM&AgNPs-gel was analyzed by investigating cell proliferation, migration, invasion, and angiogenesis capacity. Furthermore, the in vivo anti-cancer activity of HTPM&AgNPs-gel was further appraised through the tumor suppression, anti-metastatic, anti-angiogenic, and anti-inflammatory ability. The optimized HTPM&AgNPs-gel, a thermosensitive hydrogel, showed excellent properties, including syringeability, swelling behavior, and a sustained release effect without hemolysis. In addition, HTPM&AgNPs-gel was confirmed to effectively inhibit the proliferation, migration, invasion, and angiogenesis of MDA-MB-231 cells. An evaluation of the in vivo anti-tumor efficacy demonstrated that HTPM&AgNPs-gel showed a stronger tumor inhibition rate (68.17%) than did HTPM-gel or AgNPs-gel used alone and exhibited outstanding biocompatibility. Notably, HTPM&AgNPs-gel also inhibited lung metastasis induced by residual tumor tissue after surgery and further blocked angiogenesis-related inflammatory responses. Taken together, the suppression of inflammation by interdicting the blood vessels adjoining the tumor and inhibiting angiogenesis is a potential strategy to attenuate the recurrence and metastasis of TNBC. HTPM&AgNPs-gel is a promising anticancer agent for TNBC as a local postoperative treatment.

Prognostic significance of postoperative serological incomplete conversion of AFP and PIVKA-II after hepatic resection for hepatocellular carcinoma: a multicenter analysis of 1755 patients.

The value of serum biomarkers, particularly alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), gains increasing attention in prognostic evaluation and recurrence monitoring for patients with hepatocellular carcinoma (HCC). This study investigated the implications of serological incomplete conversion (SIC) of these 2 biomarkers as prognostic indicators for long-term outcomes after HCC resection. A multicenter observational study was conducted on a cohort of HCC patients presenting with AFP (>20ng/mL) or PIVKA-II (>40 mAU/mL) positivity who underwent curative-intent resection. Based on their postoperative AFP and PIVKA-II levels at first postoperative follow-up (4~8 weeks after surgery), these patients were stratified into the serological incomplete conversion (SIC) and serological complete conversion (SCC) groups. The study endpoints were recurrence and overall survival (OS). Among 1755 patients, 379 and 1376 were categorized as having SIC and SCC, respectively. The SIC group exhibited 1- and 5-year OS rates of 67.5% and 26.3%, with the corresponding recurrence rates of 53.2% and 79.0%, respectively; while the SCC group displayed 1- and 5-year OS rates of 95.8% and 62.5%, with the corresponding recurrence rates of 16.8% and 48.8%, respectively (both P < .001). Multivariate Cox regression analysis demonstrated that postoperative SIC was an independent risk factor for both increased recurrence (HR: 2.40, 95% CI, 2.04-2.81, P < .001) and decreased OS (HR: 2.69, 95% CI, 2.24-3.24, P < .001). The results emphasize that postoperative incomplete conversion of either AFP or PIVKA-II is a significant prognostic marker, indicating a higher risk for adverse oncologic outcomes following HCC resection. This revelation has crucial implications for refining postoperative adjuvant therapy and surveillance strategies for HCC patients.

NIR-responsive CN-Pt-GEM hydrogel induces necroptosis and immunotherapeutic responses prevent postoperative recurrence and wound infection in lung carcinoma

BackgroundCancer recurrence following surgical resection is a major cause of treatment failure. Finding effective methods to prevent postoperative recurrence and wound infection is an important component of successful surgery. With the development of new nanotechnology, more treatment options have been provided for postoperative adjuvant therapy. This study presents an innovative hydrogel system that stimulates tumoricidal immunity after surgical resection of non-small cell lung cancer (NSCLC) and prevents cancer relapse.ResultsThe hydrogel system is based on the excellent photothermal conversion performance of single-atom platinum (CN-Pt) along with the delivery and release of the chemotherapy drug, gemcitabine (GEM). The system is coated onto the wound surface after tumor removal with subsequent near-infrared (NIR) photothermal therapy, which efficiently induces necroptosis of residual cancer cells, amplifies the levels of damage-associated molecular patterns (DAMPs), and increases the number of M1 macrophages. The significantly higher levels of phagocytic macrophages enhance tumor immunogenicity and sensitize cancer cells to CD8 + T-cell immunity to control postoperative recurrence, which has been verified using an animal model of postoperative lung cancer recurrence. The CN-Pt-GEM-hydrogel with NIR can also inhibit postoperative wound infection.ConclusionsThese findings introduce an alternative strategy for supplementing antitumor immunity in patients undergoing resection of NSCLC tumors. The CN-Pt-GEM-hydrogel with the NIR system also exhibits good biosafety and may be adaptable for clinical application in relation to tumor resection surgery, wound tissue filling, infection prevention, and recurrence prevention.

Adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy for stage III gastric or gastro-oesophageal junction cancer after gastrectomy with D2 or more extensive lymph-node dissection (ATTRACTION-5): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial

In Asia, adjuvant chemotherapy after gastrectomy with D2 or more extensive lymph-node dissection is standard treatment for people with pathological stage III gastric or gastro-oesophageal junction (GEJ) cancer. We aimed to assess the efficacy and safety of adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy administered in this setting. ATTRACTION-5 was a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial conducted at 96 hospitals in Japan, South Korea, Taiwan, and China. Eligible patients were aged between 20 years and 80 years with histologically confirmed pathological stage IIIA-C gastric or GEJ adenocarcinoma after gastrectomy with D2 or more extensive lymph-node dissection, with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 and available tumour tissue for PD-L1 expression analysis. Patients were randomly assigned (1:1) to receive either nivolumab plus chemotherapy or placebo plus chemotherapy via an interactive web-response system with block sizes of four. Investigational treatment, either nivolumab 360 mg or placebo, was administered intravenously for 30 min once every 3 weeks. Adjuvant chemotherapy was administered as either tegafur-gimeracil-oteracil (S-1) at an initial dose of 40 mg/m2 per dose orally twice per day for 28 consecutive days, followed by 14 days off per cycle, or capecitabine plus oxaliplatin consisting of an initial dose of intravenous oxaliplatin 130 mg/m2 for 2 h every 21 days and capecitabine 1000 mg/m2 per dose orally twice per day for 14 consecutive days, followed by 7 days off treatment. The primary endpoint was relapse-free survival by central assessment. The intention-to-treat population, consisting of all randomly assigned patients, was used for analysis of efficacy endpoints. The safety population, defined as patients who received at least one dose of trial drug, was used for analysis of safety endpoints. This trial is registered with ClinicalTrials.gov (NCT03006705) and is closed. Between Feb 1, 2017, and Aug 15, 2019, 755 patients were randomly assigned to receive either adjuvant nivolumab plus chemotherapy (n=377) or adjuvant placebo plus chemotherapy (n=378). 267 (71%) of 377 patients in the nivolumab group and 263 (70%) of 378 patients in the placebo group were male; 110 (29%) of 377 patients in the nivolumab group and 115 (31%) of 378 patients in the placebo group were female. 745 patients received assigned treatment (371 in the nivolumab plus chemotherapy group; 374 in the placebo plus chemotherapy group), which was the safety population. Median time from first dose to data cutoff was 49·1 months (IQR 43·1-56·7). 3-year relapse-free survival was 68·4% (95% CI 63·0-73·2) in the nivolumab plus chemotherapy group and 65·3% (59·9-70·2) in the placebo plus chemotherapy group; the hazard ratio for relapse-free survival was 0·90 (95·72% CI 0·69-1·18; p=0·44). Treatment-related adverse events occurred in 366 (99%) of 371 patients in the nivolumab plus chemotherapy group and 364 (98%) of 374 patients in the placebo plus chemotherapy group. Discontinuation due to adverse events was more frequent in the nivolumab plus chemotherapy group (34 [9%] of 371 patients) than the placebo plus chemotherapy group (13 [4%] of 374 patients). The most common treatment-related adverse events were decreased appetite, nausea, diarrhoea, neutrophil count decreased, and peripheral sensory neuropathy. The results of this trial do not support the addition of nivolumab to postoperative adjuvant therapy for patients with untreated, locally advanced, resectable gastric or GEJ cancer. Ono Pharmaceutical and Bristol Myers Squibb.

Clinical diagnosis and treatment of 37 cases of gallbladder neuroendocrine carcinoma

ObjectiveThis study aims to investigate the clinical and pathological characteristics, treatment approaches, and prognosis of gallbladder neuroendocrine carcinoma (GB-NEC).MethodsRetrospective analysis was conducted on the clinical data of 37 patients with GB-NEC admitted to Shanxi Cancer Hospital from January 2010 to June 2023. The study included an examination of their general information, treatment regimens, and overall prognosis.ResultsTwelve cases, either due to distant metastasis or other reasons, did not undergo surgical treatment and received palliative chemotherapy (Group 1). Two cases underwent simple cholecystectomy (Group 2); four patients underwent palliative tumor resection surgery (Group 3), and nineteen patients underwent radical resection surgery (Group 4). Among the 37 GB-NEC patients, the average pre-surgery CA19-9 level was 113.29 ± 138.45 U/mL, and the median overall survival time was 19 months (range 7.89–30.11 months). Of these, 28 cases (75.7%) received systemic treatment, 25 cases (67.6%) underwent surgical intervention, and 16 cases (64.0%) received postoperative adjuvant treatment, including combined radiochemotherapy or chemotherapy alone. The median overall survival time was 4 months (0.61–7.40 months) for Group 1 (n = 12), 8 months for Group 2 (n = 2), 21 months (14.67–43.33 months) for Group 3 (n = 4), and 19 months (range 7.89–30.11 months) for Group 4 (n = 19). A significant difference in median overall survival time was observed between Group 1 and Group 4 (P = 0.004).ConclusionSurgery remains the primary treatment for GB-NEC, with radical resection potentially offering greater benefits to patient survival compared to other therapeutic options. Postoperative adjuvant therapy has the potential to extend patient survival, although the overall prognosis remains challenging.