Tumor Size Research Articles

Association of PD-L1 Expression with Clinicopathologic Characters in Gastric Cancer: A Comprehensive Meta-analysis.

The expression level of programmed death ligand-1(PD-L1) in patients with gastric cancer is the key to determining the use of immune drugs. The relationship between PD-L1 expression level and clinical characteristics is worth exploring. By setting the search terms correlated to PD-L1 and gastric cancer, a nearly comprehensive search was carried out in four major databases, and the deadline for searching was September 1, 2022. The retrieved documents were further screened by strict inclusion and exclusion criteria after removing the duplication. Next, the quality of the included studies was evaluated with the Newcastle-Ottawa Scale (NOS) scale. Finally, the STATA15.1 software was used to process data and draw plots, and the odds ratios (ORs) were adopted to assess the pooled effect size. A total of 85 works of literature were included in this study through screening strictly, and detailed data were extracted after evaluating the quality of the literature. The process of analysis was conducted in the whole population, Asia-Africa population, European and American population, and Asian population with CPS≥1, amd all found that the expression of PD-L1 in gastric cancer was correlated with age, tumor size, EBV infection, Her-2 expression and microsatellite status. However, the subgroup of the region also found some differences in Asian and Western regions, which was interesting and worth studying further. The included research of this study did not have significant publish bias. After careful analysis, this study found that age (>60 years), tumor size (>5cm), EBV infection (+), Her-2 expression (+), microsatellite status (MSI), and mismatch repair status (dMMR) were risk factors for positive expression of PD-L1 in gastric cancer.

Mathematical model for IL-2-based cancer immunotherapy

A basic mathematical model for IL-2-based cancer immunotherapy is proposed and studied. Our analysis shows that the outcome of therapy is mainly determined by three parameters, the relative death rate of CD4+ T cells, the relative death rate of CD8+ T cells, and the dose of IL-2 treatment. Minimal equilibrium tumor size can be reached with a large dose of IL-2 in the case that CD4+ T cells die out. However, in cases where CD4+ and CD8+ T cells persist, the final tumor size is independent of the IL-2 dose and is given by the relative death rate of CD4+ T cells. Two groups of in silico clinical trials show some short-term behaviors of IL-2 treatment. IL-2 administration can slow the proliferation of CD4+ T cells, while high doses for a short period of time over several days transiently increase the population of CD8+ T cells during treatment before it recedes to its equilibrium. IL-2 administration for a short period of time over many days suppresses the tumor population for a longer time before approaching its steady-state levels. This implies that intermittent administration of IL-2 may be a good strategy for controlling tumor size.

The prognostic nutritional index as a predictor of efficacy and early recurrence for adjuvant transarterial chemoembolization in hepatocellular carcinoma.

Postoperative adjuvant transcatheter arterial chemoembolization (TACE) can prevent recurrence of hepatocellular carcinoma (HCC) in certain patients. This study aimed to identify the potential beneficiaries of adjuvant TACE. 477 patients who underwent curative resection for HCC were enrolled in this retrospectively cohort study. The trajectory of the prognostic nutritional index (PNI) during the perioperative period was fitted using a latent-class growth mixed model. The association between adjuvant TACE and recurrence-free survival in each PNI group was assessed using the Kaplan-Meier curve. Furthermore, Cox regression analysis was conducted to identify the risk factors for early recurrence after adjuvant TACE and develop a nomogram model. Patients in the PNI group III had a high risk of recurrence and could benefit from adjuvant TACE (P = 0.009). The prognostic prediction model for adjuvant TACE (PAT) incorporated eight variables (PNI, tumor size, tumor number, vascular invasion, sex, aspartate aminotransferase, gamma-glutamyl transferase, and degree of differentiation). Patients with PAT scores > 330 and 235-330 had significantly higher recurrence rates than those with PAT scores < 235 (P < 0.001). PNI may help guide the selection of adjuvant TACE beneficiaries. PAT demonstrated a high accuracy in predicting the prognosis of patients who underwent postoperative TACE.

Case Report: Opposite Tumoral and Hormonal Responses to Low-dose Pasireotide in Cushing’s Disease

Background:: Pasireotide is a multireceptor somatostatin analogue approved for the treatment of patients with Cushing's disease (CD) who are ineligible or poor candidates for pituitary surgery. Here we present a patient with severe recurrent CD who was treated with pasiretide and showed opposite results between hormonal levels and pituitary tumour size. Case Presentation:: A 54-year-old woman was diagnosed with CD, a first surgical transsphenoidal procedure was performed at the time of diagnosis, and the disease recurred seven years later. She underwent a second transsphenoidal surgery, but despite apparent complete removal of the adenoma, the hypercortisolism worsened. Magnetic resonance imaging showed a tiny remnant of the adenoma adjacent to the cavernous sinus, and ketoconazole was started at a dose of 800 mg/day. Due to the persistence of pathological urinary free cortisol levels, 600 μg bid pasireotide was added. The combination therapy induced first normalisation of urinary free cortisol and later hypoadrenalism, so that ketoconazole was discontinued and pasireotide was maintained. A marked clinical improvement was achieved with pasireotide. Adrenal insufficiency persisted despite progressive tapering of the pasireotide dose to 150 mg once daily. Pituitary magnetic resonance imaging performed at 12 and 24 months during low-dose pasireotide treatment showed a few millimetres increase of the remnant. Conclusions:: This report suggests that CD Pas induces an opposite effect between hormonal profile and increase of pituitary tumor size. This peculiar phenomenon may be a consequence of the unusually low doses of pasireotide needed to control hormonal hypersecretion.

Solitary large malignant lymphoma in the head and neck region.

The present study examined the clinical characteristics of patients with a final diagnosis of solitary large malignant lymphoma of the head and neck after surgery. Between January 2015 and December 2022, 13 patients with a final diagnosis of solitary large malignant lymphoma of the head and neck after surgery were enrolled. The most common symptom of solitary large malignant lymphoma was a neck mass (n=11; 84.6%). The most common sites of the head and neck were neck level II (eight patients), neck level IV (two patients), parotid glands (two patients) and the tongue (two patients). The number of malignant lymphomas was as follows: 11 patients had one large tumor and two patients had two large tumors. The mean tumor size was 4.0±1.3 cm (range; 2.7-6.8 cm). Among the two patients with two lymphomas, the size of the second neck mass was 3.2 cm in one patient and 2.7 cm in the other patient. The most common type of solitary large malignant lymphoma was diffuse large B-cell lymphoma (n=6, 46.2%). A total of 12 patients are currently under follow-up without disease recurrence after treatment completion and one patient diagnosed 1 month ago is currently undergoing radiation therapy. The follow-up period was 47.3±19.0 months (range; 1-62 months). The possibility of solitary large malignant lymphoma of the head and neck should be considered. As it is difficult to accurately diagnose solitary large malignant lymphoma before surgery, surgical resection is required for differentiation from other diseases.

Asiaticoside promoted ferroptosis and suppressed immune escape in gastric cancer cells by downregulating the Wnt/β-catenin pathway

BackgroundOur previous study has revealed that asiaticoside (AC) promotes endoplasmic reticulum stress and antagonizes proliferation and migration of gastric cancer (GC) via miR-635/HMGA1 axis. However, the effect and mechanism of AC on other progressions of GC, such as ferroptosis and immune escape, are still unknown. MethodsAGS and HGC27 cells were incubated with 1, 2 and 4 μM of AC for 24 h. Mice xenografted with AGS cells were intragastrically injected with AC. The effect and mechanism of AC on GC were determined by the measurement of the ferrous iron level, the ROS level and the glutathione peroxidase (GSH) content, flow cytometry, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry and western blotting assays. ResultsAC increased the Fe2+ level and the ROS level, but decreased the expression of GPX4 and SLC7A11 and the GSH level. Besides, AC enhanced the percent of CD8+ T cells and the IFN-γ concentration, but reduced the PD-L1 expression and the IL-10 level. Mechanically, AC downregulated the relative levels of β-catenin, active-β-catenin, p-GSK3β/GSK3β, cyclin D1 and c-Myc in GC cells, which were rescued with the application of LiCl (an activator of Wnt/β-catenin pathway) in AGS cells. Moreover, activation of Wnt/β-catenin pathway by LiCl or the β-catenin overexpression inverted the effect of AC on ferroptosis and immune escape in GC cells. In vivo, AC treatment declined the tumor size and weight, the level of GPX4, SLC7A11, PD-L1 and IFN-γ, and the expression of Wnt/β-catenin pathway. ConclusionAC enhanced ferroptosis and repressed immune escape by downregulating the Wnt/β-catenin signaling in GC.

Hepatoblastoma: Experience of the paediatric haematology and oncology department, Hassan II university hospital of Fez.

Introduction: Hepatoblastoma is the most common malignant hepatic tumour in children. However, it is a rare disease, representing approximately 2% of childhood tumours. The treatment combines chemotherapy with surgical excision. The objective of this study was to describe the epidemiological, clinical, therapeutic and progressive aspects of hepatoblastoma treated in the paediatric haematology and oncology department at the University Hospital Hassan II of Fès. Patients and Methods: This was a descriptive and retrospective study conducted over a 11-year period. All patients aged 0 to 15 years who were admitted and treated for hepatoblastoma were included. Results: 24 patients met the study criteria, including 9 boys and 15 girls. The average age at diagnosis was 11.52 months ± 4.9. The most common reason for consultation was abdominal distension. Hepatomegaly was observed in 50% of cases. The average tumour size was 116 mm. At the time of diagnosis, one-third of patients had pulmonary metastases, and all patients were classified as high risk. Therapeutically, 19 patients (79.17%) received chemotherapy and 16 (66.67%) underwent surgery. On the evolutionary level, we observed a recovery without events in 10 (41.67%) patients. Conclusion: hepatoblastoma is a rare tumour, but remains the most common hepatic tumour in children. Despite progress in diagnostic and therapeutic means, the mortality rate is significant.

Neoadjuvant therapy with intensity-modulated radiotherapy combined with S-1 for borderline-resectable pancreatic cancer.

We evaluated the efficacy of neoadjuvant chemotherapy with intensity-modulated radiotherapy (NAC-IMRT) in patients with borderline-resectable pancreatic cancer (BRPC). BRPC patients were treated with IMRT (45Gy/15fr) combined with two courses of S-1 (40mg/m2 bid) before surgery. Outcomes after NAC-IMRT, surgery, and survival were then evaluated. This single-center retrospective study assessed 26 consecutive patients. Twenty-six patients (BR-PV: 7, BR-A: 19) with a median age of 73 years were enrolled from 2016 to 2021. Ten (38%) patients were 75-years-old and above. Twenty-three patients completed NAC-IMRT treatment. The median reductions in tumor size and cancer antigen 19-9 level were 13.6% and 69%, respectively. All 26 patients underwent resection within a median time of 71 days after NAC-IMRT initiation. R0 resection was achieved in 24 patients (92%). The median overall survival (OS) was 28.0 months, and the 1- and 3-year OS rates were 100% and 34%, respectively. The median progression-free survival (PFS) was 12.5 months, and the 1- and 3-year PFS rates were 50% and 32%, respectively. No significant differences were observed in OS between the patients under and over the age of 75 (29vs. 20 months, p=0.86). The 12 patients who completed NAC-IMRT, resection, and subsequent adjuvant chemotherapy (AC) exhibited a 3-year survival rate of 73%, which was significantly better than that of the patients who did not receive or complete AC (median OS, not reached vs. 19 months, p<0.001). NAC-IMRT showed outstanding clinical efficacy with acceptable tolerability in patients with BRPC, including geriatric patients.

Prognostic significance of MRI features in patients with solitary large hepatocellular carcinoma following surgical resection.

To assess the prognostic impact of preoperative MRI features on outcomes for single large hepatocellular carcinoma (HCC) (≥ 8 cm) after surgical resection. This retrospective study included 151 patients (mean age: 59.2 years; 126 men) with a single large HCC who underwent gadoxetic acid-enhanced MRI and surgical resection between 2008 and 2020. Clinical variables, including tumor markers and MRI features (tumor size, tumor margin, and the proportion of hypovascular component on hepatic arterial phase (AP) (≥ 50% vs. < 50% tumor volume) were evaluated. Cox proportional hazards model analyzed overall survival (OS), recurrence-free survival (RFS), and associated factors. Among 151 HCCs, 37.8% and 62.2% HCCs were classified as ≥ 50% and < 50% AP hypovascular groups, respectively. The 5- and 10-year OS and RFS rates in all patients were 62.0%, 52.6% and 41.4%, 38.5%, respectively. Multivariable analysis revealed that ≥ 50% AP hypovascular group (hazard ratio [HR] 1.7, p = 0.048), tumor size (HR 1.1, p = 0.006), and alpha-fetoprotein ≥ 400 ng/mL (HR 2.6, p = 0.001) correlated with poorer OS. ≥ 50% AP hypovascular group (HR 1.9, p = 0.003), tumor size (HR 1.1, p = 0.023), and non-smooth tumor margin (HR 2.1, p = 0.009) were linked to poorer RFS. One-year RFS rates were lower in the ≥ 50% AP hypovascular group than in the < 50% AP hypovascular group (47.4% vs 66.9%, p = 0.019). MRI with ≥ 50% AP hypovascular component and larger tumor size were significant factors associated with poorer OS and RFS after resection of single large HCC (≥ 8 cm). These patients require careful multidisciplinary management to determine optimal treatment strategies. Preoperative MRI showing a ≥ 50% arterial phase hypovascular component and larger tumor size can predict worse outcomes after resection of single large hepatocellular carcinomas (≥ 8 cm), underscoring the need for tailored, multidisciplinary treatment strategies. MRI features offer insights into the postoperative prognosis for large hepatocellular carcinoma. Hypovascular component on arterial phase ≥ 50% and tumor size predicted poorer overall survival and recurrence-free survival. These findings can assist in prioritizing aggressive and multidisciplinary approaches for patients at risk for poor outcomes.

Impact of thyroid carcinoma invasion of recurrent laryngeal nerve on cervical lymph node metastasis.

Papillary thyroid carcinoma (PTC) has a favorable prognosis. However, involvement of the recurrent laryngeal nerve (RLN) significantly increases the risk of recurrence. RLN invasion was an important factor in determining the extent of thyroid surgery. The purpose of this study was to compare clinicopathologic features and characterize risk factors of central and lateral lymph node metastasis (LLNM) of RLN invasion in patients with PTC. A retrospective review was conducted of 130 patients with PTCs who had exclusive tumor involvement of the RLN at our institution between January 2014 and February 2019. All patients underwent total thyroidectomy and high-dose radioactive iodine (RAI) therapy. The clinicopathologic factors and prognostic outcomes of the patients with solitary and multiple RLN involvements were compared. Kaplan-Meier method was performed to compare the outcomes of tumor recurrence. Univariate and multivariate logistic regression analyses were used to identify risk factors associated with LLNM. The invasion of the RLN was similar on both sides, with 58.5% on the right, 40.0% on the left, and 1.5% on both sides. Significant differences were observed in tumor size (p < 0.001), lymph node metastasis classification (p = 0.002), RLN resection (p < 0.001), and thyroglobulin (p = 0.010) in the solitary and multiple groups. During the median follow-up of 67 months, 9 (6.9%) patients developed recurrence. There were no statistical differences in recurrence for age, tumor size, gender, multifocality, lymph node metastasis (LNM), and RLN resection. According to receiver operating characteristic (ROC) curve analyses, a cut-off of tumor size > 1.7 cm was identified as the most sensitive and specific predictor of RLN with multiple involvements or LNM invasion. Univariate and multivariate analyses revealed that central lymph node metastasis (CLNM) and RLN invasion by LNM can serve as independent risk factors for LLNM (p = 0.006 and p < 0.001, respectively). Our results indicate that recurrence was comparable in patients with solitary and multiple RLN involvements. Multiple RLN involvement was associated with pathological features such as larger tumors, RLN resection, and LLNM. The presence of LNM invading RLN and multiple nerve involvement increases the risk of intraoperative RLN resection. A higher risk of multiple invasion or LNM invasion should be considered when tumor size > 1.7 cm. The presence of CLNM and RLN invaded by LNM were independent predictors for LLNM, which could aid surgeons in deciding on lateral lymph node dissection.

The Use of Chatbots in Head and Neck Mucosal Malignancy Treatment Recommendations.

As cancer patients increasingly use chatbots, it is crucial to recognize ChatGPT's potential in enhancing health literacy while ensuring validation to prevent misinformation. This study aims to assess ChatGPT-3.5's capability to provide appropriate staging and treatment recommendations for head and neck mucosal malignancies for vulnerable populations. Forty distinct clinical vignettes were introduced into ChatGPT to inquire about staging and treatment recommendations for head and neck mucosal malignancies. Prompts were created based on head and neck cancer (HNC) disease descriptions (cancer location, tumor size, lymph node involvement, and symptoms). Staging and treatment recommendations according to the 2021 National Comprehensive Cancer Network (NCCN) guidelines were scored by three fellowship-trained HNC surgeons from two separate tertiary care institutions. HNC surgeons assessed the accuracy of staging and treatment recommendations, such as the completeness of surgery and the appropriateness of treatment modality. Whereas ChatGPT's responses were 95% accurate at recommending the correct first-line treatment based on the 2021 NCCN guidelines, 55% of the responses contained inaccurate staging. Neck dissection was incorrectly omitted from treatment recommendations in 50% of the cases. Moreover, 40% of ChatGPT's treatment recommendations were deemed unnecessary. This study emphasizes ChatGPT's potential in HNC patient education, aligning with NCCN guidelines for mucosal malignancies, but highlights the importance of ongoing refinement and scrutiny due to observed inaccuracies in tumor, nodal, metastasis staging, incomplete surgery options, and inappropriate treatment recommendations. Otolaryngologists can use this information to caution patients, families, and trainees regarding the use of ChatGPT for HNC education without expert guidance.

High MAL2 expression predicts shorter survival in women with triple-negative breast cancer.

Due to its lack of conventional surface receptors, triple-negative breast cancer (TNBC) is inherently resistant to most targeted therapies. MAL2 overexpression prompts endocytosis, conferring resistance to novel therapeutics. This study explores the role of MAL2 and PD-L1 in TNBC patients' prognosis. We performed immunohistochemical analysis on 111 TNBC samples collected from 76 patients and evaluated the expression of MAL2 and PD-1. We expanded the study by including The Cancer Genome Atlas (TCGA) cohort. MAL2 expression did not correlate with stage, grade, tumor size, lymph node invasion, metastasis, and PD-1 expression. Patients with high MAL2 had significantly lower 5-year survival rates (71.33% vs. 89.59%, p = 0.0224). In the tissue microarray cohort (TMA), node invasions, size, recurrence, and low MAL2 (HR 0.29 [CI 95% 0.087-0.95]; p < 0.05) predicted longer patients' survival. In the TCGA cohort, patients with low MAL2 had significantly longer overall survival and disease-specific survival than patients with high MAL2. Older age and high MAL2 expression were the only independent predictors of shorter patient survival in the BRCA TCGA cohort. High MAL2 predicts unfavorable prognosis in triple-negative breast cancer, and its expression is independent of PD-1 levels and clinicopathological features of TNBC.

Predictive Value of Pre-treatment Hematological Parameters for Response to Definitive Chemoradiation in Locally Advanced Cervical Cancer: A Prospective Study

Background: More than 90% of cervical cancers are related to chronic inflammation caused by HPV. Several studies have shown that laboratory hematological parameters can detect the severity of systemic inflammation. Objectives: Our current cohort study investigated the predictive role of pretreatment hematological parameters for response to definitive chemoradiotherapy in patients with locally advanced cervical cancer (LACC). Methods: Prospectively, patients with LACC who candidates for definitive chemoradiation at Shohadaye Haftom-e-Tir are and Firozgar Hospitals (Tehran, Iran) were included in our study between April 2021 and December 2022. Hematological parameters were obtained from the blood sample test and peripheral blood smear before treatment. All patients diagnosed in stage IB to IVA received a similar treatment protocol and follow-up. Patients were divided into complete clinical (CR) and non-complete clinical responses (Non-CR). Leukocyte, Lymphocyte, neutrophil, platelet, hemoglobin (Hb), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR), were documented and then compared between two groups of responders. We used receiver operating characteristic (ROC) analysis to investigate the predictive value of these hematological parameters. Results: Out of 34 patients who met the inclusion criteria, 25 (73/5%) patients were complete responders and 9 (26.5%) were non-complete responders. The average number of neutrophils, leukocytes, and NLR was significantly higher among Non-complete responders. Hemoglobin in patients with non-complete responses was significantly lower than that of the other group of responders. Receiver operating characteristic curve analysis showed that the optimized cut-off values for pretreatment Hb and NLR were 11 and 2.1, respectively. Neutrophil-to-lymphocyte ratio cut-off point &gt; 2.1 is significantly associated with larger tumor size, low Hb, high platelet, and high leukocyte. Conclusions: hematological markers such as NLR can be a simple and inexpensive predictive factor to evaluate therapeutic response to chemoradiation in LACC patients.

Colorectal Sarcomatoid Carcinoma: 30-Year Experience.

Background: Primary colorectal sarcomatoid carcinoma is a rare and aggressive malignant neoplasm that displays mixed epithelial and mesenchymal differentiation, with uncertain histogenesis. First described in 1986, there is a paucity of literature related to this condition and there are no evidence-based treatment guidelines. The aim of our study is to present our 30-year experience with primary colorectal sarcomatoid carcinoma. Methods: Retrospective single-center analysis of all patients treated for primary colorectal sarcomatoid carcinoma from 1992 to 2022. The primary outcome was response to treatment strategy and overall survival. Results: A total of six cases met eligibility criteria. Three were male (50%) with a mean age at diagnosis of 59years (range, 49-72). Four neoplasms were located in the rectum (66%) and two in the colon. Mean tumor size at diagnosis was 4.8cm (range, 2.8-7.0). Three patients were treated endoscopically and three underwent oncologic surgical resection. Five experienced recurrence and one expired from other comorbidities. The mean survival among those with colonic and rectal sarcomatoid carcinoma was 7months (range, 3-11) and 39months (range, 9-60), respectively. Discussion: Primary colorectal sarcomatoid carcinoma is a rare malignant tumor with poor prognosis. Treatment modalities have not been standardized and despite multimodal therapy, disease recurrence and/or metastasis is likely to occur. Further studies are necessary to determine optimal treatment to improve outcomes.

Characteristics of her2-positive breast cancer, and the current use of anti-her2 therapy and its related factors

ABSTRACT Objective: To describe the characteristics of patients with HER2-positive breast cancer and to identify the proportion of patients using anti-HER2 therapy, and treatment-making related factors. Methods: An analytical cross-sectional study was conducted on 79 patients with BC and HER2-positive diagnosed by immunohistochemistry (IHC) or with FISH at the Oncology Department of Hue University of Medicine and Pharmacy Hospital and Oncology Center of Hue Central Hospital from 1/2021 to 12/2022. Clinical and pathological features, type of drug, number of cycles using anti-Her2 therapy were recorded using medical documents. The decision-making related factors were recorded by questionnaire interviewing patients and relatives. Exclusion criteria included recurrent or previously treated tumors; having contraindications with anti-HER2 therapy; not being willing to participate in the study. SPSS 22.0 was used for the analysis. Results: Mean age was 54.14 ± 11.03. Patients with right-sided BC accounted for 53.1%. 60.8% of tumors were located in the upper right quadrant of the breast. Patient’s self-report of lumps was the most common cause of hospitalization (77.2%). By ultrasound, 60.2% of participants had a tumor size of 2 - 5cm. Abnormal lymph nodes were identified in 40.8% of patients. Histopathologically, invasive ductal carcinoma was found in the majority of tumors (75.9%). Stage II was predominant with 59.5% and 7.6% of patients with stage IV. The rate of treatment with Trastuzumab in our study was 27.8%. The main reason that patients refused anti-HER-2 therapy was financial problems (96.5%). The awareness of anti-HER2 therapy among patients and their relatives was significantly associated with the treatment decision (p = 0.007). Conclusion: Regarding the positive-HER2 BC patients, invasive ductal carcinoma was the major histopathological finding. More than half of the patients were classified as stage II of the disease. The rate of patients undergoing antiHER2 therapy was 27.8%. Financial problems were found to be the main reason for refusal of treatment. Awareness of anti-HER2 therapy is significantly associated with the patient’s decision on treatment.

IL-2-free tumor-infiltrating lymphocyte therapy with PD-1 blockade demonstrates potent efficacy in advanced gynecologic cancer

BackgroundTumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer.MethodsPatient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence.ResultsIn matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p < 0.0001) and underwent IL-2 absence in vivo. In the clinical section, all enrolled patients received TIL infusion using a modified TIL therapy regimen successfully with a manageable safety profile. Five (36%, 95% CI 16.3–61.2) out of 14 evaluable patients experienced objective responses, and three complete responses were ongoing at 19.5, 15.4, and 5.2 months, respectively. Responders had longer overall survival (OS) than non-responders (p = 0.036). Infused TILs showed continuous proliferation and long-term persistence in all patients and showed greater proliferation in responders which was indicated by the Morisita overlap index (MOI) of TCR clonotypes between infused TILs and peripheral T cells on day 14 (p = 0.004) and day 30 (p = 0.004). Higher alteration of the CD8+/CD4+ ratio on day 14 indicated a longer OS (p = 0.010).ConclusionsOur modified TIL therapy regimen demonstrated manageable safety, and TILs could survive and proliferate without IL-2 intravenous administration, showing potent efficacy in patients with advanced gynecologic cancer.Trial registrationNCT04766320, Jan 04, 2021.

Risk factor analysis and nomogram development and verification for medullary carcinoma of the colon using SEER database

Medullary Carcinoma of the Colon (MCC) is a rare histological subtype of colon cancer, and there is currently no recognized optimal treatment plan for it, with its prognosis remaining unclear. The aim of this study is to analyze the independent prognostic factors for MCC patients and develop and validate nomograms to predict overall survival (OS). A total of 760 patients newly diagnosed with MCC from 2004 to 2020 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. All patients were randomly allocated to a training group and a validation group in a 7:3 ratio. Univariate and multivariable Cox regression analyses were conducted to identify prognostic factors and construct nomograms. The nomogram prediction model was evaluated and validated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The study found that elderly women are more susceptible to MCC, and the ascending colon and cecum are the most common sites of involvement. MCC is poorly differentiated, with stages II and III being the most common. Surgery is the primary treatment for MCC. The prognosis for patients with stage IV MCC is poor, with a median survival time of only 10 months. Independent prognostic factors for MCC include age, N stage, M stage, surgery, chemotherapy, and tumor size. Among them, age < 75 years and completion of chemotherapy were protective factors for colon medullary carcinoma, while N2 (HR = 2.18, 95%CI 1.40–3.38), M1 (HR = 3.31, 95%CI 2.01–5.46), no surgery (HR = 27.94, 95%CI 3.69–211.75), and tumor diameter > 7 cm (HR = 1.66, 95%CI 1.20–2.30) were risk factors for colon medullary carcinoma. The results of ROC, AUC, calibration curves, and DCA demonstrate that the nomogram prediction model exhibits good predictive performance. We have updated the demographic characteristics of colon medullary carcinoma and identified age, N staging, M staging, surgery, chemotherapy and tumor size as independent prognostic factors for colon medullary carcinoma. Additionally, we have established nomograms for prognostic prediction. These nomograms can provide personalized predictions and serve as valuable references for clinical decision-making.

PSO-PSP-Net + InceptionV3: An optimized hyper-parameter tuned Computer-Aided Diagnostic model for liver tumor detection using CT scan slices

An automated diagnostic system leads to a supreme requirement in medical image analysis, greatly impacting the death rate due to the high spreading rate of liver tumors. However, the traditional histopathological diagnostic processes cause more disruption in the medical detection framework because of the procedure of manual estimation of CT scans and medical labor-intensive, which lead to the time consumption process. It is a highly challenging task for the segmentation of liver tumor because of the irregular appearance, distinct densities, patchy edges, and tumor sizes. To overcome this issue, an automated computer-aided diagnosis framework has been utilized to diagnose the liver cancer quickly and accurately with the less workload of expert radiologists.Presently, Deep learning-based techniques have been applied to identify the tumor regions and assist radiologists in the initial diagnosis and scrutinizing the severity level. The proposed work presents a modified pyramid scene parsing network (PSP-Net) model based on InceptionV3 deep network architecture with a particle swarm optimization algorithm, which increases the efficiency and effectiveness of the liver diagnostic model. Three publicly accessible benchmark datasets have been engaged with the pre-processing task accomplished by image normalization and data augmentation techniques. Moreover, a hyper-parameter tuned improved PSO-PSP-Net algorithm has analyzed the optimal set of gathered features. In the experimental evaluation, the proposed model outperformed than grey wolf optimization (GWO-PSP-Net), PSO-U-Net, GWO-U-Net, opposition based spotted hyena optimization (O-SHO-CRNN), and grey wolf-class topper optimization (GW-CTO) + U-Net by 8.42 %, 4.9 %, 9.54 %, 5.12 %, and 1.75 %, respectively in terms of accuracy for LiTS dataset. The developed PSO-PSP-Net model attained better accuracy than GWO-PSP-Net, PSO-U-Net, GWO-U-Net, and Residual Atrous U-Net (RA-U-Net) for the segmentation of Type-I and Type-II liver tumors by 6.88 %, 8.44 %, 13.75 %, 5.99 % and 6.12 %, 9.74 %, 17.3 %, and 5.11 %, respectively for 3DIRCAD-b1 dataset. The obtained accuracy of the developed model is 14.09 %, 7.54 %, 16.36 %, 2.64 %, and 14.9 %, 8.86 %, 17.76 %, and 4.87 % maximized than GWO-PSP-Net, PSO-U-Net, GWO-U-Net, and RA-U-Net, respectively, for the segmentation of the infected arteries and bones in the 3DIRCAD-b1 dataset. For the CHAOS dataset, the improved PSO-PSP-Net model outperformed GWO-PSP-Net, PSO-U-Net, and GWO-U-Net, respectively, in terms of overall accuracy by 7.44 %, 8.85 %, and 17.2 %, respectively. The investigational analysis validates the proposed PSO-PSP-Net model's effectiveness and performance in obtaining high segmentation accuracy in comparison with other state-of-the-art approaches.

RAS/RAF mutations and microsatellite instability status in primary colorectal cancers according to HER2 amplification.

HER2 amplification-associated molecular alterations and clinicopathologic features in colorectal cancers (CRCs) have not been well established. In this study, we assessed the prevalence of HER2 amplification and microsatellite instability (MSI) status of 992 patients with primary CRC. In addition, molecular alterations of HER2 amplified and unamplified CRCs were examined and compared by next-generation sequencing. HER2 amplifications were found in 41 (4.1%) of 992 primary CRCs. HER2 amplification was identified in 1.0% of the right colonic tumors, 5.1% of the left colonic tumors, and 4.8% of the rectal tumors. Approximately 95% of HER2 amplification was observed in the left colon and rectum. Seven (87.5%) of eight metastatic tumors showed HER2 amplification. Most clinicopathologic features were unrelated to HER2 amplification except tumor size and MSI status. All 41 HER2 amplified CRCs were microsatellite stable. In a molecular analysis of frequently identified somatic mutations in CRCs, HER2 amplified CRCs showed a lower rate of KRAS mutations (24.4%) but a higher rate of TP53 mutations (83%) than unamplified CRCs. No BRAF and NRAS mutations were identified in HER2 amplified CRCs. Our study suggests that HER2 amplified CRCs are mutually exclusive of MSI and harbor less frequent KRAS/NRAS/BRAF mutations but frequent T53 mutations.

NGEF is a potential prognostic biomarker and could serve as an indicator for immunotherapy and chemotherapy in lung adenocarcinoma.

Neuronal guanine nucleotide exchange factor (NGEF) plays a key role in several cancers; however, its role in lung adenocarcinoma (LUAD) remains unclear. The aim of this study was to evaluate the efficacy of NGEF as a prognostic biomarker and potential therapeutic target for LUAD. NGEF expression data for multiple cancers and LUAD were downloaded from multiple databases. The high- and low-NGEF expression groups were constructed based on median NGEF expression in LUAD samples, and then performed Kaplan-Meier survival analysis. Differentially expressed genes (DEGs) from the two NGEF expression groups were screened and applied to construct a protein-protein interaction network. The primary pathways were obtained using gene set enrichment analysis. The associations between NGEF expression and clinical characteristics, immune infiltration, immune checkpoint inhibitors (ICIs), sensitivity to chemotherapy, and tumor mutation burden (TMB) were investigated using R. Levels of NGEF expression in the lung tissue was validated using single-cell RNA sequencing, quantitative polymerase chain reaction (qPCR), immunohistochemical staining, and western blot analysis. The expression of NGEF mRNA was upregulated in multiple cancers. mRNA and protein expression levels of NGEF were higher in patients with LUAD than in controls, as validated using qPCR and western blot. High NGEF expression was an independent prognostic factor for LUAD and was associated with advanced tumor stage, large tumor size, more lymph node metastasis, and worse overall survival (OS). A total of 182 overlapping DEGs were screened between The Cancer Genome Atlas and GSE31210, among which the top 20 hub genes were identified. NGEF expression was mainly enriched in the pathways of apoptosis, cell cycle, and DNA replication. Moreover, elevated NGEF expression were associated with a high fraction of activated memory CD4+ T cells and M0 macrophages; elevated expression levels of the ICIs: programmed cell death 1 and programmed cell death 1 ligand 1 expression; higher TMB; and better sensitivity to bortezomib, docetaxel, paclitaxel, and parthenolide, but less sensitivity to axitinib and metformin. NGEF expression is upregulated in LUAD and is significantly associated with tumor stages, OS probability, immune infiltration, immunotherapy response, and chemotherapy response. NGEF may be a potential diagnostic and prognostic biomarker and therapeutic target in LUAD.