Stage T1-T2 Research Articles

Clinical correlation of p16 expression with lymphatic invasion and epithelial-mesenchymal transition (EMT) in oropharyngeal carcinomas

Background/Aim To examine the clinical correlation of p16 expression with Epithelial–Mesenchymal Transition (EMT) markers and lymphatic invasion in OPSCC patients in terms of clinical status at presentation, subsequent progression, and survival. Methods Tissue blocks of biopsy-proven Oropharyngeal Squamous Cell Carcinoma were subjected to Immunohistochemistry (IHC) for evaluating the expression of p16, e-cadherin, vimentin and podoplanin. This expression pattern was correlated with the demographic details, treatment response and survival patterns. Results 60 patients were finally available for evaluation in this study. Prevalence of HPV infection in our study was found to be 11.7%. E-cadherin expression was found in all HPV-associated patients whereas vimentin was not expressed in any of these. 71.4% patients had low Podoplanin expression and 85.7% had low lymphatic vessel count. Among the HPV- associated patients, 85.8% had T3-T4 stage, 100% had N2-N3 disease and 95% had stage IV disease. It was also found that p16-positive patients had significantly higher 1-year Overall survival (OS) (80%, p=0.045), higher 1-year Progression-free survival (PFS) (60%) and higher 1-year Locoregional recurrence-free survival (LRRFS) (75%) when compared to p16-negative patients. Conclusion Prevalence of HPV infection was found to be similar to that of previous studies conducted in India. As previous literature suggests, the HPV-positive patients in our study presented with advanced nodal disease at presentation and thereby, an advanced overall stage. Further follow-up of these patients including their treatment details, determination of possible prognostic markers, and evaluation of their survival parameters can be done which can help in modifying the existing treatment modalities as HPV-associated OPSCC are known to have better prognosis according to literature.

Risk Factor Analysis and Prediction of Para-Aortic Lymph Node Metastases in Locally Advanced Cervical Cancer.

The indications of prophylactic extended-field radiotherapy (EFRT) remain uncertain. This study aims to identify the risk factors for para-aortic lymph node (PALN) metastases in locally advanced cervical cancer (LACC) and determine which part of patients may benefit from prophylactic EFRT. Between January 2015 and July 2023, a single-center retrospective analysis was performed on patients with stages IB3 and IIA2-IVA cervical cancer. Lymph node involvement was assessed using positron emission tomography/computed tomography (PET/CT). Risk factors were evaluated by logistic regression. A prediction nomogram model was developed and validated. Among 329 patients, 64 (19.5%) had PALN metastases. Univariate analysis indicated that tumor size > 5.3 cm, tumor maximum standardized uptake value (SUVmax) > 9.8, bilateral pelvic lymph node (PLN) metastases, the number of positive PLNs ≥ 3, and T3-T4 stages were related to PALN metastases. After multivariate logistic analysis, it was found that tumor size > 5.3 cm (odds ratio [OR] = 3.129, 95% confidence interval [CI] = 1.536-6.374, p = 0.002), and the number of positive PLNs ≥ 3 (OR = 11.260, 95% CI = 3.506-36.158, p < 0.001) were independent risk factors. The C-index of the nomogram was 0.886 (95% CI = 0.844-0.927). The calibration plot showed that the nomogram was well-fitted. Decision curve analysis (DCA) exhibited excellent clinical utility. Tumor size > 5.3 cm and the number of positive PLNs ≥ 3 are independent risk factors of PALN metastases. The nomogram shows pretty good accuracy, which may provide a valuable reference for guiding patients who are very likely to develop PALN metastases to receive prophylactic EFRT.

Machine learning and deep learning models for preoperative detection of lymph node metastasis in colorectal cancer: a systematic review and meta-analysis.

To evaluate the diagnostic performance of Machine Learning (ML) and Deep Learning (DL) models for predicting preoperative Lymph Node Metastasis (LNM) in Colorectal Cancer (CRC) patients. A systematic review and meta-analysis were conducted following PRISMA-DTA and AMSTAR-2 guidelines. We searched PubMed, Web of Science, Embase, and Cochrane Library databases until February 16, 2024. Study quality and risk of bias were assessed using the QUADAS-2 tool. Data were analyzed using STATA v18, applying random-effects models to all analyses. Twelve studies involving 8321 patients were included, with most published in 2021-2024 (9/12). The pooled AUC of ML models for predicting LNM in CRC patients was 0.87 (95% CI: 0.82-0.91, I2:86.17) with a sensitivity of 78% (95% CI: 69-87%) and a specificity of 77% (95% CI: 64%-90%). In addition, when assessing the AUC reported by radiologists, both junior and senior radiologists had similar performance, significantly lower than the ML models. (P < 0.001). Subgroup analysis revealed higher AUCs in prospective studies (0.95, 95% CI: 0.87-1) compared to retrospective studies (0.85, 95% CI: 0.81-0.89) (P = 0.03). Studies without external validation exhibited significantly higher AUCs than those with external validation (P < 0.01). While there was no significant difference in AUC and sensitivity between the T1-T2 and T2-T4 stages, specificity was significantly higher in the T2-T4 stages than the low stages of T1 and T2 (95%, 95% CI: 92-98% vs. 61%, 95% CI: 44-78%; P < 0.01). ML models demonstrate strong potential for preoperative LNM staging and treatment planning in CRC, potentially reducing the need for additional surgeries and related health and financial burdens. Further prospective multicenter studies, with standardized reporting of algorithms, modality parameters, and LNM staging, are needed to validate these findings.

AR expression-independent XRCC3 mediates DNA damage-induced p53/Bax signaling pathway activation against prostate cancer

BackgroundAndrogen deprivation therapy (ADT) resistance is closely associated with altered AR status. Aberrant AR expression is critical for the induction of ADT resistance, necessitating the identification of an anti-PCa target independent of AR expression.MethodsTranscriptomic data and clinical information of PRAD were obtained from TCGA database. Genes with PCa-related and AR expression-independent were screened by bioinformatics, and characterized by PPI and GO functional enrichment analyses. Candidate genes were locked by co-expression correlation and disease-free survival (DFS) analyses. A prognostic gene set was established using LASSO Cox regression algorithm. Cox proportional risk regression was performed to identify a key prognostic gene. Expression of the target protein in PCa tissues was verified by The Human Protein Atlas database. In vitro validation of cellular function and molecular mechanism by knockdown and overexpression of the target gene.ResultsTwo AR expression-independent genes (SLC43A1 and XRCC3) were available for the optimal prognostic model. This gene set effectively predicted PRAD patients’ DFS at 1-, 3- and 5-year, where XRCC3 and tumor (T) stage were independent risk factors. XRCC3 was higher expressed in PRAD patients with T3-T4 stages and accompanied by poorer DFS. IHC staining also validated its higher expression in high-risk PCa tissues. In vitro experiments demonstrated that silencing XRCC3 significantly inhibited 22Rv1 and DU145 cell proliferation, migration and invasion, while promoted apoptosis. Further, silencing XRCC3 promoted DNA damage-induced p53/Bax signaling pathway activation, which was absent with overexpression.ConclusionSilencing XRCC3 exerts anti-PCa effects by promoting DNA damage-induced p53/Bax signaling pathway activation in an AR expression-independent manner.

Survival Risk Score for Invasive Nonmetastatic Breast Cancer: A Real-World Analysis.

This study aimed to develop a multivariable, weighted overall survival (OS) risk score (SRS) for nonmetastatic (M0) invasive breast cancer (M0-BC, SRSM0-BC). This study included a training (1,890 patients) and a validation cohort (850 patients) from the Reggio Emilia Cancer Registry (RE-CR). Ten traditional prognostic variables were evaluated. In the training set, all the variables but the human epidermal growth factor receptor were significantly associated with OS at univariable analysis. A multivariable model identified an increased death risk for estrogen receptor (hazard ratio [HR], 2.0 [95% CI, 1.1 to 3.1]; P = .021), tumor stages T2-T3 (HR, 2.4 [95% CI, 1.3 to 4.7]; P = .009) and T4 (HR, 5.1 [95% CI, 2.0 to 13.0]; P < .001), and age >74 years (HR, 5.7 [95% CI, 4.0 to 8.2]; P < .001). By assigning scores according to HRs, four risk categories were generated (P for trend <.001). The HRs of death in the high- (282 patients, 15.6%), intermediate-high (275 patients, 15.2%), and intermediate-risk (349 patients, 19.2%) categories patients were, respectively, 27.3, 12.9, and 3.5 times higher, compared with the low-risk (909 patients, 50%) group. Harrell'C index was 81.1%, and the explained variation in mortality was 66.6. Internal cross-validation performed on the accrual index dates yielded a Harrell'C index ranging from 79.5% to 82.3% and an explained variation in mortality ranging from 60.3% to 69.4%. In the validation set, the same risk categories (P for trend <.001) were devised. The Harrell'C index and the explained variation in mortality were 76.1% and 53.7%, respectively, in the whole cohort, maintaining an elevated percentage according to the two accrual index dates. SRSM0-BC using the real-world RE-CR data set may represent a low-cost, accessible, globally applicable model in daily clinical practice, helping to prognostically stratify patients with invasive M0-BC.

Application of Surface Plasmon Resonance Imaging Biosensors for Determination of Fibronectin, Laminin-5, and Type IV Collagen in Plasma, Urine, and Tissue of Renal Cell Carcinoma.

Laminin, fibronectin, and collagen IV are pivotal extracellular matrix (ECM) components. The ECM environment governs the fundamental properties of tumors, including proliferation, vascularization, and invasion. Given the critical role of cell-matrix adhesion in malignant tumor progression, we hypothesize that the concentrations of these proteins may be altered in the plasma of patients with clear cell renal cell carcinoma (ccRCC). This study aimed to evaluate the serum, urine, and tissue levels of laminin-5, collagen IV, and fibronectin among a control group and ccRCC patients, with the latter divided into stages T1-T2 and T3-T4 according to the TNM classification. We included 60 patients with histopathologically confirmed ccRCC and 26 patients diagnosed with chronic cystitis or benign prostatic hyperplasia (BPH). Collagen IV, laminin-5, and fibronectin were detected using Surface Plasmon Resonance Imaging biosensors. Significant differences were observed between the control group and ccRCC patients, as well as between the T1-T2 and T3-T4 subgroups. Levels were generally higher in plasma and tissue for fibronectin and collagen IV in ccRCC patients and lower for laminin. The ROC (Receiver operating characteristic) analysis yielded satisfactory results for differentiating between ccRCC patients and controls (AUC 0.84-0.93), with statistical significance for both fibronectin and laminin in plasma and urine. Analysis between the T1-T2 and T3-T4 groups revealed interesting findings for all examined substances in plasma (AUC 0.8-0.95). The results suggest a positive correlation between fibronectin and collagen levels and ccRCC staging, while laminin shows a negative correlation, implying a potential protective role. The relationship between plasma and urine concentrations of these biomarkers may be instrumental for tumor detection and staging, thereby streamlining therapeutic decision-making.

Dosimetric Evaluation of Hippocampus Sparing Intensity Modulated Radiation Therapy in Patients With Stage T1-T2 and Stage T3-T4 Nasopharyngeal Carcinoma

PurposeTo compare the hippocampus (HPC) dose reduced by HPC-sparing IMRT plans between nasopharyngeal carcinoma (NPC) patients of stages T1-T2 and T3-T4, and to investigate the correlation between the dose of the hippocampus and the volume of PTVnx70 (the planning target volume of the primary tumor in the nasopharynx received 70 Gy). Methods and MaterialsFifty-eight NPC patients were retrospectively evaluated. HPC non-sparing IMRT or sparing IMRT for each patient was designed according to the protocol for NPC. Dose-volume histogram (DVH) was used to evaluate the IMRT plans for each patient. The difference values of HPC parameters (e.g., Dmin[NS] - Dmin[S]) between HPC sparing and non-sparing plans in stage T1-T2 Group and stage T3-T4 Group were compared. The correlations between the dose of the hippocampus and the volume of PTVnx70 were analyzed. ResultsThere was no significance between HPC-sparing and non-sparing IMRT plans. Compared with the HPC non-sparing plans, the HPC sparing plans significantly decreased both dosimetric and volumetric parameters for the HPC (P < 0.05), except for Dmin, D98%, and V5. The medians of Dmedian[NS] - Dmedian[S], Dmean[NS] - Dmean[S], D40%[NS] - D40%[S], V30[NS] - V30[S], V40[NS] - V40[S] and V50[NS] - V50[S] in the T1-T2 Group were significantly lower than in the T3-T4 Group (P < 0.05), respectively. Both dosimetric and volumetric parameters for the HPC were positively correlated with the volume of PTVnx70 in HPC-sparing and non-sparing plans (P < 0.05). The volume of PTVnx70 was positively correlated with Dmedian[NS] - Dmedian[S], Dmean[NS] - Dmean[S], D40%[NS] - D40%[S], V40[NS] - V40[S] and V50[NS] - V50[S] (P < 0.05). ConclusionsHPC-sparing IMRT plans may play a more significant role in decreasing Dmedian, Dmean, D40%, and V30 ∼ V50 of HPC in NPC patients with stages T3-T4 than those in stages T1-T2. PTVnx70 volume of NPC patients are positively correlated with all dosimetric and volumetric parameters of HPC and the reduction of specific dosage parameters by HPC-sparing IMRT plans.

Image-guided Hypofractionated Radiotherapy as an Alternative to Radical Prostatectomy in Localized Prostate Cancer in Elderly Patients with Low Life Expectancy.

Radical prostatectomy is appropriate for any patient whose cancer appears clinically localised to prostate. However because of potential perioperative morbidity, radical prostatectomy is generally reserved for patients whose life expectancy is more than ten years. Moderate hypofractionation for localized prostate cancer is safe and effective. There is a growing body of evidence in support of extreme hypofractionation for localized prostate cancer. Hypofractionation for prostate cancer was originally carried out in the pursuit of efficiency and convenience, but has now attracted greatly renewed interest based upon a hypothesis that prostate cancers have a higher sensitivity to fraction size, reflected in a low α/β ratio, then do late responding organs at risk such as the rectum or bladder. From January 2017 to December 2020 we treated 112 patients of localised Prostate Cancer with Image Guided Radiotherapy (IGRT). They were in range of 75-85 years. They were of stage T1-T3, N0 or N1. There were significant comborbidities. ECOG performance status was 0-1. They were given 3 months of Androgen Deprivation Therapy (ADT) before starting IGRT. Patients were immobilised with casts and subject to CT simulation. CBCT was taken daily. Dose was 70 Gy @ 250 cGy per fraction at a frequency of 5 fractions per week. Complete blood counts were done weekly for assessment of haematological toxicity. Androgen Deprivation Therapy was continued post IGRT. All the patients were able to complete the treatment. Evaluation was done at one month, three month and six months post treatment. 104 out of 112 patients achieved complete response. Other 8 had near complete response. There were no acute grade 3-4 toxicities. Grade 1-2 toxicities like skin desquamation, diarrhoea, burning micturition were managed conservatively. Late toxicity was rectal bleeding seen after one year of completion of treatment and was managed with steroid enemas. 23 patients required argon plasma laser therapy. Image guided radiotherapy is well tolerated, easy to implement and an effective alternative to radical prostatectomy in elderly patients with comorbidities and low life expectancy.

TRANSCRIPTOME PROFILING AND EXAMINATION OF INDIVIDUALS DIAGNOSED WITH ESOPHAGEAL SQUAMOUS CELL CARCINOMA ORIGINATING FROM KAZAKHSTAN

Esophageal cancer stands as the eighth most prevalent cancer globally and the sixth most prevalent in Kazakhstan, with esophageal squamous cell carcinoma (ESCC) as its primary histological subtype, often diagnosed in advanced stages. This project aimed to unveil the genetic underpinnings of ESCC by examining differentially expressed genes (DEGs) via whole-transcriptome sequencing of Kazakhstani patients. Tissue samples from 22 individuals undergoing Ivor-Lewis esophagectomy at the Oncology Center in Astana were collected. Utilizing STAR software and DESeq2 package, DEGs were mapped and defined, followed by functional analysis using various R packages. The study encompassed 13 males and 9 females, averaging 65.72 ± 8.26 years old, with 86% diagnosed at advanced stages T3-T4. Analysis of tumor and normal esophageal tissues unveiled 6689 DEGs, including 2056 upregulated and 4633 downregulated genes (adjusted p-value &lt;0.05). Additionally, 42 up-regulated and 2 down-regulated KEGG pathways were identified (p-value &lt;0.05). The top 300 DEGs were mapped to a protein-protein interaction (PPI) network, and functional enrichment analysis revealed three modules comprising closely connected genes. Within our patient cohort, ESCC with moderate dysplasia emerged as the most prevalent histologic subtype, associated with poor prognosis. High-throughput sequencing techniques facilitate the identification of molecular pathways implicated in esophageal carcinogenesis, potentially revolutionizing diagnosis and treatment strategies. This research has been funded by the Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan (Program targeted funding BR18574184 and grant AP09058660), and Nazarbayev University funding CRP grant 021220CRP2222.

Impacts of 18F-FDG PET/CT Parameters on Differential Diagnosis and Outcome of Patients with Primary Invasive Mucinous and Lepidic Predominant Adenocarcinoma of the Lung.

The purpose of this study was to investigate whether 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters have a role in differentiating invasive mucinous lung adenocarcinoma (IMA) from lepidic predominant lung adenocarcinoma (LPA). Additionally, we compared the 18F-FDG-PET/CT features between survivors and non-survivors. Tumors were divided into 2 groups according to CT appearance: Group 1: nodular-type tumor; group 2: mass- or pneumonic-type tumor. Unilateral and bilateral multifocal diseases were detected. Clinicopathological characteristics and PET/CT findings were compared between IMAs and LPAs, as well as between survivors and non-survivors. We included 43 patients with IMA and 14 with LPA. Tumor size (p=0.003), incidence of mass/pneumonic type (p=0.011), and bilateral lung involvement (p=0.049) were higher in IMAs than in LPAs. IMAs had more advanced T, M, and Tumor, Node, and Metastasis stages than in LPAs (p=0.048, p=0.049, and p=0.022, respectively). There was no statistically significant difference in maximum standardized uptake value (SUVmax) between the IMA and LPA (p=0.078). The SUV was significantly lower in the nodular group than in the mass/pneumonic-type group (p=0.0001). A total of 11 patients died, of whom SUVmax values were significantly higher in these patients (p=0.031). Male gender (p=0.0001), rate of stage III-IV (p=0.0001), T3-T4 (p=0.021), M1 stages (p=0.0001), multifocality (p=0.0001), and bilateral lung involvement (p=0.0001) were higher in non-survivor. Although CT images were useful for the differential diagnosis of LPAs and IMAs, SUVmax was not helpful for differentiation of these 2 groups. However, both 18F-FDG uptake and CT findings may play an important role in predicting prognosis in these patients.

Ultra-Hypofractionated Whole Breast Radiotherapy with Automated Hybrid-VMAT Technique: A Pilot Study on Safety, Skin Toxicity and Aesthetic Outcomes.

The most prevalent treatment-related side effect related to adjuvant radiotherapy (RT) for breast cancer is acute skin toxicity in the irradiated area. The purpose of this single-institution pilot study is to provide preliminary clinical results on the feasibility and safety of a breast ultra-hypofractionated radiation treatment delivered using an automated hybrid-VMAT technique. Skin damage was assessed both with clinical examination and objectively using a Cutometer equipment. Patients received 26 Gy to the whole breast and 30 Gy to the tumoral bed in 5 fractions using an automated hybrid-VMAT approach with the option for the breath hold technique if necessary. Acute and late toxicities were clinically evaluated at baseline, 1- and 6-months after treatment using the CTC-AE v.5.0 scale. An instrumental evaluation of the skin elasticity was performed using a Cutometer® Dual MP580. Two parameters per patient, R0 (the total skin firmness) and Q1 (the elastic recovery), were registered at the different timelines. From June 2022 to January 2024, 30 patients, stage T1-T2, N0 were enrolled in the study. Four out of 30 (13.3%) patients reported G2 acute skin toxicities. At 6 months, G2 late toxicity was registered in 3 patients (10%). A total of 2160 measures of R0 and Q1 were recorded. At 1 month after treatment, no correlation was found between measured values of R0 and Q1 and clinical evaluation. At 6 months after treatment, clinical late toxicity ≥1 was strongly associated with decreased R0 and Q1 values ≥24% (p = 0.003) and ≥18% (p = 0.022), respectively. Ultra-hypofractionated whole-breast radiotherapy, when supported by advanced treatment techniques, is both feasible and safe. No severe adverse effects were observed at any of the different timeframes. Acute and late skin toxicities were shown to be lower in contrast to data presented in the literature.

The Dilemma for Early-Stage Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma: To Treat or Not to Treat?

Primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (MALToma) is typically treated with radiotherapy. Some studies suggested a "wait and watch" approach due to the adverse effects of radiotherapy. However, the benefits of observation for localized conjunctival MALToma remain unclear. Therefore, we aimed to explore the clinical course of early-stage conjunctival MALToma, distinguish heterogeneity between T1 and T2 patients, and identify prognostic factors. This retrospective study involved patients with stage T1-T2 conjunctival MALToma and lasted >6 months. Clinical characteristics were compared between T1 and T2 subjects. Prognostic factors were examined with Cox regression. The research comprised 32 subjects with early-stage conjunctival MALToma, of whom 25% underwent observation. No individuals expired regardless of choosing observation or radiotherapy. The T1 patients were younger (p = 0.002) and more inclined towards observation only (p = 0.035) than the T2 subjects. Despite more of the T1 patients undergoing watchful waiting than the T2 subjects, the T1 patients seemed to have longer systemic relapse-free survival than the T2 subjects (17 vs. 13 years, p = 0.343). CD43 may imply poor prognosis (p = 0.049). Careful observation may be suggested for early-stage conjunctival MALToma. While more of the T1 individuals were younger and chose observation than the T2 patients, survival seemed longer in the T1 subjects without significance. CD43 may indicate shorter survival in early-stage cases.

Prognostic and clinicopathological value of the controlling nutritional status (CONUT) score in patients with head and neck cancer: a meta-analysis

BackgroundThe efficiency of controlling nutritional status (CONUT) score in detecting the prognosis of head and neck cancer (HNC) patients has been investigated in some works, but no consistent findings are obtained. Therefore, this work focused on evaluating the precise prognostic role of CONUT for HNC patients through meta-analysis.MethodsThe effect of CONUT on predicting the prognosis of HNC patients was evaluated through calculating combined hazard ratios (HRs) as well as 95% confidence intervals (CIs). The correlations of CONUT with clinicopathological features of HNC patients were investigated through combined odds ratios (ORs) and 95%CIs. This study used the random-effects model in the case of significant heterogeneity; or else, we selected the fixed-effects model.ResultsThere were eight articles involving 1,478 patients enrolled for the current meta-analysis. We adopted the fixed-effects model for OS and DFS analysis because of the non-significant heterogeneity. As demonstrated by our combined findings, high CONUT score could significantly predict the poor overall survival (OS) (HR = 1.94, 95%CI = 1.55–2.44, p < 0.001) and disease-free survival (DFS) (HR = 1.93, 95%CI = 1.45–2.56, p < 0.001) of HNC. In addition, higher CONUT score was significantly connected to T3-T4 stage (OR = 3.21, 95%CI = 1.94–5.31, p < 0.001) and N1-N3 stage (OR = 3.10, 95%CI = 1.74–5.53, p < 0.001).ConclusionAccording to findings in the present meta-analysis, high CONUT score significantly predicted the prognosis of OS and DFS for HNC patients. Higher CONUT score was also correlated to larger tumor size and LN metastasis in HNC. Due to it is a cost-effective and easily available parameter, CONUT could serve as promising prognostic biomarker for HNC.

Assessing Axillary Lymph Node Burden and Prognosis in cT1-T2 Stage Breast Cancer Using Machine Learning Methods: A Retrospective Dual-Institutional MRI Study.

Pathological axillary lymph node (pALN) burden is an important factor for treatment decision-making in clinical T1-T2 (cT1-T2) stage breast cancer. Preoperative assessment of the pALN burden and prognosis aids in the individualized selection of therapeutic approaches. To develop and validate a machine learning (ML) model based on clinicopathological and MRI characteristics for assessing pALN burden and survival in patients with cT1-T2 stage breast cancer. Retrospective. A total of 506 females (range: 24-83 years) with cT1-T2 stage breast cancer from two institutions, forming the training (N = 340), internal validation (N = 85), and external validation cohorts (N = 81), respectively. This study used 1.5-T, axial fat-suppressed T2-weighted turbo spin-echo sequence and axial three-dimensional dynamic contrast-enhanced fat-suppressed T1-weighted gradient echo sequence. Four ML methods (eXtreme Gradient Boosting [XGBoost], Support Vector Machine, k-Nearest Neighbor, Classification and Regression Tree) were employed to develop models based on clinicopathological and MRI characteristics. The performance of these models was evaluated by their discriminative ability. The best-performing model was further analyzed to establish interpretability and used to calculate the pALN score. The relationships between the pALN score and disease-free survival (DFS) were examined. Chi-squared test, Fisher's exact test, univariable logistic regression, area under the curve (AUC), Delong test, net reclassification improvement, integrated discrimination improvement, Hosmer-Lemeshow test, log-rank, Cox regression analyses, and intraclass correlation coefficient were performed. A P-value <0.05 was considered statistically significant. The XGB II model, developed based on the XGBoost algorithm, outperformed the other models with AUCs of 0.805, 0.803, and 0.818 in the three cohorts. The Shapley additive explanation plot indicated that the top variable in the XGB II model was the Node Reporting and Data System score. In multivariable Cox regression analysis, the pALN score was significantly associated with DFS (hazard ratio: 4.013, 95% confidence interval: 1.059-15.207). The XGB II model may allow to evaluate pALN burden and could provide prognostic information in cT1-T2 stage breast cancer patients. 3 TECHNICAL EFFICACY: Stage 2.

Amide proton transfer-weighted MRI for assessing rectal adenocarcinoma T-staging and perineural invasion: a prospective study.

To investigate the value of the pre-operative amide proton transfer-weighted (APTw) MRI to assess the prognostic factors in rectal adenocarcinoma (RA). This prospective study ran from January 2022 to September 2023 and consecutively enrolled participants with RA who underwent pre-operative MRI and radical surgery. The APTw signal intensity (SI) values of RA with various tumor (T), node (N) stages, perineural invasion (PNI), and tumor grade were compared by Mann-Whitney U-test or t-test. The receiver operating characteristic curve was used to evaluate the diagnostic performance of the APTw SI values. A total of 51 participants were enrolled (mean age, 58 years ± 10 [standard deviation], 26 men). There were 24 in the T1-T2 stage and 9 with positive PNI. The APTw SI max, 99th, and 95th values were significantly higher in T3-T4 stage tumor than in T1-T2; the median (interquartile range) (M (IQR)) was (4.0% (3.6-4.9%) vs 3.4% (2.9- 4.3%), p = 0.017), (3.7% (3.2-4.1%) vs 3.2% (2.8-3.8%), p = 0.013), and (3.3% (2.8-3.8%) vs 2.9% (2.3-3.5%), p = 0.033), respectively. These indicators also differed significantly between the PNI groups, with the M (IQR) (4.5% (3.6-5.7%) vs 3.7% (3.2-4.2%), p = 0.017), (4.1% (3.4-4.8%) vs 3.3% (3.0-3.9%), p = 0.022), and (3.7% (2.7-4.2%) vs 2.9% (2.6-3.5%), p = 0.045), respectively. Pre-operative APTw MRI has potential value in the assessment of T-staging and PNI determination in RA. Pre-operative amide proton transfer-weighted MRI provides a quantitative method for noninvasive assessment of T-staging and PNI in RA aiding in precision treatment planning. The efficacy of APTw MRI in RA needs further investigation. T3-T4 stage and PNI positive APTw signal intensities were higher than T1-T2 and non-PNI, respectively. APTw MRI provides a quantitative method for assessment of T staging and PNI in RA.

Transoral Robotic Surgery and Human Papillomavirus Infection: Impact on Oropharyngeal Cancer Prognosis.

Background/Objective: The incidence of oropharyngeal cancer (OPC) remains significant, with a rising prevalence of HPV-positive (HPV+) cases, underscoring the growing importance of appropriate treatment approaches for this condition. While HPV+ OPC typically exhibits a more favorable prognosis than HPV-negative (HPV-) OPC, certain HPV+ OPC patients still face adverse outcomes. This study aimed to assess the effectiveness of TORS versus traditional surgery in treating OPC patients and investigate the prognostic implications of specific variants in the HPV genome. Methods: The clinical information, including pathological features, treatments, and outcomes (death), of 135 OPC patients treated with traditional surgery from 2008 to 2018 (the non-TORS group) and 130 OPC patients treated with TORS from 2017 to 2021 (the TORS group) were obtained from Sun Yat-sen University Cancer Center (SYSUCC). A comparative analysis of 3-year overall survival (OS) was performed between these two groups. Furthermore, we conducted next-generation sequencing for the HPV16 genome of the 68 HPV+ OPC cases to characterize single-nucleotide variations (SNVs) in the HPV16 genome and evaluate its association with HPV+ OPC patient survival. Results: The comparative analysis of 3-year OS between the two groups (TORS vs. non-TORS) revealed a significant prognostic improvement in the TORS group for OPC patients with a T1-T2 classification (89.3% vs. 72.0%; p = 1.1 × 10-2), stages I-II (92.1% vs. 82.2%; p = 4.6 × 10-2), and stages III-IV (82.8% vs. 62.2%; p = 5.7 × 10-2) and for HPV- patients (85.5% vs. 33.3%; p < 1.0 × 10-6). Furthermore, three SNVs (SNV1339A>G, SNV1950A>C, and SNV4298A>G) in the HPV16 genome were identified as being associated with worse survival. These SNVs could alter protein interactions and weaken the binding affinity for MHC-II, promoting viral amplification and immune evasion. Conclusions: TORS exhibited a superior prognosis to traditional surgery in OPC patients. Additionally, identifying specific SNVs within the HPV16 genome provided potential prognostic markers for HPV+ OPC. These significant findings hold clinical relevance for treatment decision-making and prognostic assessment in patients with OPC.

Increased infiltration of M2-polarized tumour-associated macrophages is highly associated with advanced disease stage and high expression of PD-L1 in buccal mucosa carcinoma

ObjectiveTo assess the infiltration characteristics of tumour-associated macrophages (TAMs) in buccal mucosa carcinoma (BMC) and the correlation of these features with clinicopathological factors.Materials and methodsImmunohistochemistry was used to detect the expression of TAM-related markers (CD68, CD163, CD206), CD8+ T cell markers, PD-L1, and epidermal growth factor receptor (EGFR) in 46 patients with mucosal cancer after radical surgery. In addition, the correlation between TAM infiltration and clinical characteristics, PD-L1 expression, and EGFR expression was analysed.ResultsA high infiltration level of M2-polarized (CD206+) TAMs and M2-polarized (CD163+) TAMs was more common in stage T3–T4, N+, III–IV patients than in other patient groups (P < 0.05). The infiltration degree of M2-polarized (CD68+) TAMs was positively correlated with the PD-L1 TPS (P = 0.0331). The infiltration level of M2-polarized (CD206+) TAMs was higher in the EGFR high expression group than in the EGFR low expression group (P = 0.040).ConclusionHigh infiltration of M2-polarized TAMs is highly associated with advanced disease stage and higher expression of PD-L1 and EGFR in BMCs, suggesting that M2-polarized TAMs infiltration can serve as a potential therapeutic target.

Genome-Wide Methylation Patterns in Primary Uveal Melanoma: Development of MethylSig-UM, an Epigenomic Prognostic Signature to Improve Patient Stratification.

Despite studies highlighting the prognostic utility of DNA methylation in primary uveal melanoma (pUM), it has not been translated into a clinically useful tool. We sought to define a methylation signature to identify newly diagnosed individuals at high risk for developing metastasis. Methylation profiling was performed on 41 patients with pUM with stage T2-T4 and at least three years of follow-up using the Illumina Infinium HumanMethylation450K BeadChip (N = 24) and the EPIC BeadChip (N = 17). Findings were validated in the TCGA cohort with known metastatic outcome (N = 69). Differentially methylated probes were identified in patients who developed metastasis. Unsupervised consensus clustering revealed three epigenomic subtypes associated with metastasis. To identify a prognostic signature, recursive feature elimination and random forest models were utilized within repeated cross-validation iterations. The 250 most commonly selected probes comprised the final signature, named MethylSig-UM. MethylSig-UM could distinguish individuals with pUM at diagnosis who develop future metastasis with an area under the curve of ~81% in the independent validation cohort, and remained significant in Cox proportional hazard models when combined with clinical features and established genomic biomarkers. Altered expression of immune-modulating genes were detected in MethylSig-UM positive tumors, providing clues for pUM resistance to immunotherapy. The MethylSig-UM model is available to enable additional validation in larger cohort sizes including T1 tumors.

Efficacy of chemoradiotherapy in elderly patients with stage IV inoperable head and neck cancer.

This study aimed to compare the efficacy of chemoradiotherapy (CRT) with radiotherapy (RT) alone for elderly patients (≥ 65 years) with stage IV inoperable head and neck cancer (IV-HNC). Elderly patients diagnosed with inoperable IV-HNC from 2010 to 2015 were identified using the SEER database. Then, we performed a 1:1 propensity-score matched (PSM) analysis to reduce treatment selection bias, and the prognostic role of CRT was investigated using Kaplan-Meier analysis, log-rank test, and Cox proportional hazard models. The main outcome was overall survival (OS), and the secondary outcome was cancer-specific survival (CSS). A total of 3318 patients were enrolled, of whom 601 received RT alone and 2717 received CRT. Through PSM, 526 patients were successfully matched, and balances between the two treatment groups were reached. In the matched dataset, multivariable Cox analysis revealed that CRT was associated with better OS (HR = 0.580, P < 0.001) and CSS (HR = 0.586, P < 0.001). Meanwhile, subgroups of patients with IV-HNC (younger age, male sex, being married, black race, grade I-II, oral cavity site, T3-T4 stage, N0-N1 stage, M1 stage) were inclined to benefit more from CRT treatment. Furthermore, the survival benefit of CRT was more pronounced in patients aged 65 to 80 years, but was absent in patients aged 80 years or older. This study indicated that CRT resulted in better survival than RT alone in elderly patients with inoperable IV-HNC, especially for those subpopulations that benefit more from CRT treatment.

Short-term OS as a surrogate endpoint for 5-year OS in nasopharyngeal carcinoma in non-endemic area

PurposeTo address this evidence gap and validate short-term OS at less than 5 years as a reliable surrogate endpoint for 5-year OS.MethodsWe analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, focusing on non-metastatic NPC patients diagnosed between 2010 and 2015. Patients were categorized into radiotherapy and chemoradiotherapy groups.ResultsThis retrospective study examined 2,047 non-metastatic NPC patients. Among them, 217 received radiotherapy, and 1,830 received chemoradiotherapy. Our analysis results indicated that the 4-year OS may serve as a reliable surrogate endpoint for patients with AJCC clinical stage I (80 vs. 78%, P = 0.250), regardless of the treatment received. Specifically, in the radiotherapy group, patients with stage I, T0-T1, and N0 NPC showed similar OS rates at 4 and 5 years (83 vs. 82%, P = 1.000; 78 vs. 76%, P = 0.250; 78 vs. 77%, P = 0.500, respectively). Similarly, patients with stage II-IV, T2-T4, and N1-3 NPC showed no significant difference in OS rates between 3 and 5 years (57 vs. 51%, P = 0.063; 52 vs. 46%, P = 0.250; 54 vs. 46%, P = 0.125, respectively) in the radiotherapy group. In the chemoradiotherapy group, only the 3-year OS rate did not significantly differ from that at 5 years in stage I patients (79vs. 72%, P = 0.063).ConclusionsOur study suggests that short-term surrogate endpoints may be valuable for evaluating 5-year OS outcomes in NPC patients in non-endemic areas.