Cancer Management and Research最新文献

Patients with advanced gastroesophageal junction (GEJ) adenocarcinoma typically exhibit poor clinical outcomes, especially with brain metastases (BMs). Here, we present a notable patient with HER-2 positive advanced gastric cancer complicated with large-volume BMs who achieved long-term survival reaching 9 years through multidisciplinary treatment strategy encompassing abdominal radiotherapy, stereotactic radiosurgery (SRS), targeted therapy, and systemic chemotherapy. These findings highlight the need for balancing efficacy and safety to develop individualized radiotherapy strategies for large-volume BMs. This outcome highlights the potential benefits of comprehensive approaches and the feasibility of proactive local interventions for oligoprogressive disease. This case provides valuable experience for managing similar cases and offers new ideas for combining novel modalities like antibody-drug conjugates (ADC) drugs, immunotherapy, and radiotherapy.

Background: Platinum-resistant recurrent ovarian cancer remains a major therapeutic challenge. Immune checkpoint inhibitors (ICIs) combined with chemotherapy are widely used, but clinical benefits remain limited. Thymosin α1 (Tα1), an immunomodulatory peptide, may synergize with ICIs to enhance anti-tumor immunity.

Methods: This retrospective study included 386 patients with PROC, with 193 patients receiving Tα1 combined with PD-1/PD-L1 inhibitors and chemotherapy (experimental group), and 193 patients receiving PD-1/PD-L1 inhibitors and chemotherapy alone (control group). Baseline clinical characteristics, clinical efficacy, immune parameters, progression-free survival (PFS), and adverse events were compared between the two groups. Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression were used to assess PFS and associated prognostic factors. Continuous and categorical variables were compared using t-test and χ² -test, respectively. Statistical significance was defined as p < 0.05.

Results: Baseline characteristics were comparable between the two groups. The experimental group showed significantly higher objective response rate (43% vs 30.2%; p = 0.008) and disease control rate (87% vs 69.8%; p = 0.000). The median PFS was significantly longer in the experimental group (3.0 vs 1.1 months; HR = 3.22, 95% CI: 2.59-4.01; p = 0.000). Post-treatment, patients in the experimental group demonstrated significantly elevated levels of IgA, IgG, IgM, CD3⁺, CD4⁺, CD4⁺/CD8⁺ ratio, and NK cells compared to the control group (all p < 0.01), while CD8 levels remained similar. The incidence of adverse events was lower in the experimental group (50.8% vs 65.8%; χ² = 8.35, p = 0.004), primarily due to a reduced rate of myelosuppression.

Conclusion: The addition of Tα1 to PD-1/PD-L1 inhibitor-based chemotherapy may enhance treatment efficacy, improve immune response, and reduce immunosuppression-related toxicity in patients with platinum-resistant recurrent ovarian cancer.

Background: Patients with locally advanced rectal cancer (LARC) have considerable rates of postoperative recurrence and metastasis, and existing scoring systems lack specificity. This study aims to establish and validate a prognostic model using inflammatory nutritional index CALLY for overall survival (OS) and progression-free survival (PFS) in patients with LARC following neoadjuvant chemoradiotherapy (NACRT), with the goal of enabling early risk assessment and intervention in LARC patients.

Methods: One hundred and thirty-one LARC patients were analyzed undergoing NACRT followed by surgery (January 2020-May 2024). The median follow-up was 27 months. LASSO regression and multivariate Cox analysis identified prognostic factors. Nomograms for 2-/3-year OS and PFS were constructed and validated using KM, time-dependent ROC curves, calibration plots, and decision curve analysis (DCA). Bootstrap method was used to internally verify the nomogram model.

Results: The study's multifactorial analysis revealed high CALLY were independently associated with improved OS (HR = 0.344, 95% CI: 0.133-0.893; P = 0.028) and PFS (HR = 0.492, 95% CI: 0.266-0.912; P = 0.024). OS nomogram (CALLY/CEA/CCI) achieved AUCs of 0.83 (2-year) and 0.76 (3-year). PFS nomogram (CALLY/PLR/CEA/CA724/vascular invasion) showed superior 3-year accuracy (AUC = 0.81) but lower 2-year accuracy (AUC = 0.71). Calibration curves confirmed good prediction-observation agreement. DCA revealed wider clinical applicability for 3-year PFS. Survival KM curve for OS suggested that high-risk patients had 8.25-fold higher mortality (95% CI: 3.05-22.30).

Conclusion: A prognostic nomogram of LARC patients after NACRT in terms of OS and PFS was established based on the inflammatory nutritional Index CALLY, in which the PFS model showed excellent long-term predictive accuracy and clinical utility, providing individualized risk stratification and advance intervention to guide adjuvant therapy.

Background: Pancreatic cancer is most often diagnosed at an advanced stage because it develops silently, and its early symptoms are vague and nonspecific. Grouping patients by their primary symptom clusters could provide valuable prognostic insights, enabling more accurate predictions of the stage at diagnosis, the likelihood of surgical resection, and expected survival.

Methods: Single-center retrospective cohort study of 164 adults with histologically confirmed pancreatic adenocarcinoma. Patients were grouped by primary symptom cluster: obstructive (jaundice/dark urine/pruritus/steatorrhea), systemic (anorexia, fatigue, weight loss, or dyspnea/neurologic), pain-predominant (abdominal/back/epigastric pain or acute pancreatitis), or control (asymptomatic/incidental).

Results: The study included 164 patients with a median age of 69 years (range 57-81); 56.7% were male. At diagnosis, the overall stage distribution was as follows: stage I, 11%; stage II, 15.9%; stage III, 24.4%; and stage IV, 48.8%. Patients in the obstructive, systemic, and pain-predominant groups were more likely to present with advanced disease than those in the control group (p<0.05). Among the symptomatic groups, the systemic cluster had a higher proportion of advanced-stage cases compared with both the obstructive and pain-predominant groups (p<0.05). In contrast, no difference was found between the obstructive and pain-predominant groups (p>0.05). In Cox proportional hazards analysis, symptom cluster category, stage at diagnosis, surgical resection status, treatment rate, treatment type, and localization were identified as independent predictors of overall survival (p<0.05). Median survival was longest in the control group (37.6 months), followed by the obstructive (16.0 months), pain-predominant (11.8 months), and systemic (7.8 months) groups, with all between-group comparisons reaching significance (p<0.05).

Conclusion: Presenting symptom clusters are strongly associated with disease stage, surgical resectability, and survival outcomes in pancreatic cancer. Early recognition of high-risk symptom profiles may improve surgical opportunities and outcomes.

Triple-negative breast cancer (TNBC) is highly malignant with poor prognosis, and immune checkpoint inhibitors (ICIs) provide only limited survival benefits. A key emerging subtype is HER2 low-expressing TNBC, where HER2 expression influences immune microenvironment, clinical behavior, and therapeutic response. Antibody-drug conjugates (ADCs), particularly trastuzumab deruxtecan (T-DXd), have markedly improved survival and also exert antitumor effects through immune activation. Preclinical data suggest synergy when T-DXd is combined with ICIs. However, HER2-low TNBC often has an immune-suppressive microenvironment, underscoring the need for additional strategies. Tumor vaccines and genomics-driven targeted drugs, such as trastuzumab-α-amanitin conjugates, hold promise in reactivating antitumor immunity. This review summarizes current progress in immunotherapy for HER2 low-expressing TNBC, with emphasis on ADCs, combination regimens, and emerging precision strategies, aiming to inform future research and clinical application.

Keratin 17 (KRT17), a type I intermediate filament protein normally restricted to basal epithelia and hair follicles, is aberrantly overexpressed across diverse aggressive malignancies where it correlates strongly with poor prognosis. Beyond driving core oncogenic processes like cell proliferation, migration, apoptosis evasion, and metabolic reprogramming, KRT17 is increasingly recognized as a pivotal regulator of cancer therapy resistance. Mechanistically, KRT17 induces chemoresistance in multiple cancers through distinct pathways: activating AKT/ERK signaling and epithelial-mesenchymal transition (EMT) in bladder cancer; modulating Wnt/β-catenin in triple-negative breast cancer; influencing the EMT/Snail2/E-cadherin axis in cervical cancer; and engaging FAK/SRC/ERK/CXCL8 immunosuppression in pancreatic cancer. It also contributes to resistance in gastric, thyroid, and skin cancers via EMT, AKT/mTOR, and immune evasion. While KRT17 predominantly drives therapy resistance and immunosuppression across various malignancies, it exhibits a contrasting, context-dependent role in colorectal cancer, where its expression is associated with enhanced T-cell infiltration and improved response to immunotherapy. Given its cancer-specific overexpression, multifaceted role in malignancy (including resistance), and promising preclinical evidence that targeting KRT17 can reverse resistance, KRT17 emerges as a significant diagnostic/prognostic biomarker and a compelling therapeutic target. This review critically synthesizes evidence for KRT17's role in drug resistance and evaluates its potential for overcoming this major barrier to successful cancer treatment.

Objective: To analyze the relationship between the standardized uptake value (SUV) derived from 18F-FDG PET/CT imaging and the clinical characteristics of colon cancer, and to evaluate its diagnostic performance relative to CT imaging in identifying lymph node metastasis.

Methods: A retrospective analysis was conducted on 113 patients with pathologically confirmed primary colon cancer. All patients underwent preoperative 18F-FDG PET/CT and CT examinations. The SUV of the primary lesion was measured. Patients were grouped based on clinicopathological features, and differences in SUV across groups were analyzed. The diagnostic efficacy of PET/CT and CT for lymph node metastasis was evaluated using receiver operating characteristic (ROC) curves, with pathology as the gold standard.

Results: The lesion SUV was not significantly related to sex, age, lesion location, CA199, or CA242 (P > 0.05). However, it was significantly associated with maximum lesion diameter (P < 0.001), AJCC stage (P = 0.001), pathological type (P < 0.001), differentiation grade (P < 0.001), lymph node metastasis (P < 0.001), and CEA expression (P < 0.001). Spearman correlation analysis showed that SUV was positively correlated with these significant parameters (all P < 0.05). For diagnosing lymph node metastasis, the area under the curve (AUC) for 18F-FDG PET/CT imaging was 0.943, which was significantly higher than that for CT imaging (0.836) (Z = 3.965, P < 0.05), with superior sensitivity and specificity.

Conclusion: SUV values on 18F-FDG PET/CT are positively correlated with key indicators of tumor aggressiveness in colon cancer, including tumor size, stage, differentiation grade, and lymph node metastasis. 18F-FDG PET/CT demonstrates significantly better diagnostic performance than CT alone for the detection of lymph node metastasis.

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment regimen for locally advanced rectal cancer (LARC). However, pathologic complete response (pCR) rates remain suboptimal, and distant metastasis remains a significant cause of treatment failure. While immune checkpoint inhibitors (ICIs) has demonstrated promising efficacy and safety in microsatellite instability-high (MSI-H) rectal cancer patients, less than 5% of rectal cancers exhibit MSI-H characteristics. The majority are microsatellite stable (MSS) types, which are generally unresponsive to immunotherapy alone. Recent studies have indicated that the addition of radiotherapy can convert immune checkpoint-insensitive "cold" tumors into more responsive "hot" tumors. Therefore, combining immunotherapy with nCRT may enhance the pCR rate and improve prognosis in LARC patients.

Objective: The study aimed to evaluate the safety and efficacy of serplulimab in combination with conventional nCRT for treating LARC, particularly in patients with high-risk factors.

Methods: A retrospective analysis was conducted using data from patients with LARC treated at the First Affiliated Hospital with Nanjing Medical University between November 2023 and July 2024. All enrolled patients received conventional radiotherapy combined with CapeOX or capecitabine monotherapy, along with serplulimab, followed by TME 8-12 weeks post-nCRT. The primary endpoint was the pCR rate, while secondary endpoints included the incidence of adverse events.

Results: A total of 29 patients were enrolled, with a median age of 60 years. About 79.3% patients had tumors located within 10 cm from the anal margin. Pre-treatment stages were uniformly categorized as IIIB or IIIC, with 51.7% classified as cT4 and 86.2% as cN2. Additionally, 65.5% exhibited tumor invasion of the mesorectal fascia. All 29 patients underwent R0 resection. Postoperative pathology revealed that 31.0% (9/29) patients achieved tumor regression grade (TRG) 0, 31.0% (9/29) patients achieved TRG 1. The most common adverse events included lymphocytopenia, fatigue, neutropenia, and anal pain. Grade 3 toxicity was observed in 48.3% of patients, with no grade 4 or 5 adverse reactions noted.

Conclusion: The combination of serplulimab with nCRT demonstrated safety and efficacy in patients with high-risk pMMR LARC. However, further verification through longer follow-up periods and large-scale prospective studies is warranted.

Purpose: This study focused on developing and testing a comprehensive model that explores the social determinants of health influencing the quality of life of young breast cancer survivors, particularly highlighting the impact of treatment regret.

Methods: This descriptive-analytical study with a cross-sectional design was conducted on 462 young female breast cancer survivors referred to the Yazd Radiation Therapy Center. Data were collected using a demographic questionnaire, the standard decision regret scale, the perceived social support scale, the reproductive concern inventory, and the quality-of-life questionnaire for breast cancer survivors. Then, using path analysis test, the relationship between social determinants of health and quality of life in breast cancer survivors was examined. Data were analyzed by SPSS-26 and LISREL-8 software.

Results: According to the results of path analysis, among the structural determinants of health examined, socioeconomic status (β=0.279) had the most positive effect on the quality of life. Also, among the intermediate determinants, treatment regret (β=-0.26) and fertility concerns (β=-0.36) had the most direct and negative effect on the quality of life of breast cancer survivors. The fertility concerns had the most indirect and negative effect on the quality of life of young female survivors with the mediation of treatment regret (β=-0.039). The results also indicated an acceptable goodness of fit for the model.

Conclusion: Socioeconomic status had the strongest influence on the quality of life of young breast cancer survivors, partly through social support. Fertility concerns also affected quality of life directly and indirectly via treatment regret. Addressing fertility-related distress should be a key component of supportive care. Although fertility preservation options such as egg or embryo freezing exist in Iran, limited access and awareness highlight the need for early fertility counseling and integrated psychosocial support to improve survivors' well-being.

Implications for cancer survivors: To improve their quality of life, it is essential to implement strategies such as creating support groups in treatment centers, offering counseling on fertility options, and providing regular follow-up programs for their physical and mental health.

Background: Primary gastric malignant melanoma (PGMM) is an exceedingly rare non-epithelial tumor. Only a limited number of cases have been documented, posing significant diagnostic and therapeutic challenges.

Case presentation: A 75-year-old man presented with cough and sputum. Computed tomography (CT) suggested a malignant tumor with multiorgan metastasis. Gastroscopy revealed multiple polypoid lesions, and histopathology confirmed melanoma. After multidisciplinary discussion, primary gastric melanoma was diagnosed. Despite aggressive treatment, the disease progressed rapidly, and the patient died six months after diagnosis.

Conclusion: This case highlights the importance of early endoscopy in patients with metastatic tumors of unknown origin. Although outcomes remain poor, this report contributes to the understanding of PGMM diagnosis and management.