Primary Tumor Stage Research Articles

LINC00365 as a potential biomarker for total nephrectomy in advanced-stage renal cell carcinoma patients

BackgroundRenal cell carcinoma (RCC) is one of the most frequent urological cancers globally that has a good prognosis in the early tumor stages. However, there is a poor prognosis in metastatic RCC patients. Therefore, it is needed to evaluate the molecular biology of RCC progression to introduce the efficient diagnostic and therapeutic markers in these patients. Long non-coding RNAs (lncRNAs) have key roles in regulation of molecular mechanisms during RCC progression. In the present study, we assessed the levels of LINC00365 expressions in RCC patients to suggest that as a tumor marker in these patients. MethodsFifty fresh RCC tumor tissues and their normal margins were collected to assess the levels of LINC00365 expressions and probable correlations with clinicopathological features of RCC patients. ResultsThere was significant LINC00365 up regulation in females compared with males (p=0.050). Among the RCC patients with total nephrectomy, there was a significant LINC00365 up regulation in advanced stage compared with primary stage tumors (p=0.035). RCC patients older than 60 years old who were undergone the total nephrectomy had also significant LINC00365 up regulation compared with RCC patients younger than 60 years old (p=0.039). Conclusionsgiven the significant increase in LINC00365 expression in advanced stage RCC tumors and patients over 60 years old who had total nephrectomy; it could serve as a useful diagnostic marker in screening programs for old high-risk individuals. It was also noticed that female RCC patients had elevated levels of LINC00365 expressions in their tumor samples, suggesting its potential use as a gender-specific diagnostic marker for high-risk females. Nevertheless, evaluating the levels of LINC00365 in serum samples of RCC patients is necessary to suggest that as a reliable diagnostic marker in clinical settings.

Androgen receptor expression and clinical characteristics in breast cancer

ObjectiveTo investigate the relationship between the expression of androgen receptor (AR) and clinical characteristics in breast cancer.Patients and methodsThe clinical records of all 432 patients tested for AR in our institution between January 2020 and May 2023 were reviewed. Clinical characteristics, age, menopausal status, tumor node metastasis (TNM) stage, distant metastasis, pathological complete response (pCR), histopathological features histological grade, estrogen receptor (ER), progesterone receptor, Her-2, Ki-67, and molecular subtype were registered for all patients.ResultsAbout 377 (87.27%) of the 432 patients had AR expression.No significant difference in AR expression was found with age, menopausal status, TNM stage of primary tumor, or pCR. AR was positively and significantly associated with the histological grade, and recurrence. The AR expression was significantly related with molecular subtypes, including ER, PR Her-2, Ki67 and molecular subtype. ER (OR = 10.489, 95%CI: 5.470–21.569), PR (OR = 7.690, 95%CI: 3.974–16.129, Her-2 (OR = 10.489, 95%CI: 2.779–23.490 and tumor recurrence (OR = 0.110, 95%CI: 0.031–0.377 were significant independent risk factors affecting AR expression.ConclusionsAR expression can serve as a reliable basis for judging the clinical molecular types and poor prognosis for breast cancer. AR may be a novel biomarker and target in AR-positive breast cancer depending on significant difference in AR expression among different molecular types of breast cancer.

Intravoxel incoherent motion diffusion-weighted imaging in evaluating preoperative staging of esophageal squamous cell carcinoma

BackgroundThe aim of this research is to prospectively investigate the diagnostic performance of intravoxel incoherent motion (IVIM) using the integrated slice-specific dynamic shimming (iShim) technique in staging primary esophageal squamous cell carcinoma (ESCC) and predicting presence of lymph node metastases from ESCC.MethodsSixty-three patients with ESCC were prospectively enrolled from April 2016 to April 2019. MR and IVIM using iShim technique (b = 0, 25, 50, 75, 100, 200, 400, 600, 800 s/mm2) were performed on 3.0T MRI system before operation. Primary tumour apparent diffusion coefficient (ADC) and IVIM parameters, including true diffusion coefficient (D), pseudodiffusion coefficient (D*), pseudodiffusion fraction (f) were measured by two independent radiologists. The differences in D, D*, f and ADC values of different T and N stages were assessed. Intraclass correlation coefficients (ICCs) were calculated to evaluate the interobserver agreement between two readers. The diagnostic performances of D, D*, f and ADC values in primary tumour staging and prediction of lymph node metastasis of ESCC were determined using receiver operating characteristic (ROC) curve analysis.ResultsThe inter-observer consensus was excellent for IVIM parameters and ADC (D: ICC = 0.922; D*: ICC = 0.892; f: ICC = 0.948; ADC: ICC = 0.958). The ADC, D, D* and f values of group T1 + T2 were significantly higher than those of group T3 + T4a [ADC: (2.55 ± 0.43) ×10− 3 mm2/s vs. (2.27 ± 0.40) ×10− 3 mm2/s, t = 2.670, P = 0.010; D: (1.82 ± 0.39) ×10− 3 mm2/s vs. (1.53 ± 0.33) ×10− 3 mm2/s, t = 3.189, P = 0.002; D*: 46.45 (30.30,55.53) ×10− 3 mm2/s vs. 32.30 (18.60,40.95) ×10− 3 mm2/s, z=-2.408, P = 0.016; f: 0.45 ± 0.12 vs. 0.37 ± 0.12, t = 2.538, P = 0.014]. The ADC, D and f values of the lymph nodes-positive (N+) group were significantly lower than those of lymph nodes-negative (N0) group [ADC: (2.10 ± 0.33) ×10− 3 mm2/s vs. (2.55 ± 0.40) ×10− 3 mm2/s, t=-4.564, P < 0.001; D: (1.44 ± 0.30) ×10− 3 mm2/s vs. (1.78 ± 0.37) ×10− 3 mm2/s, t=-3.726, P < 0.001; f: 0.32 ± 0.10 vs. 0.45 ± 0.11, t=-4.524, P < 0.001]. The combination of D, D* and f yielded the highest area under the curve (AUC) (0.814) in distinguishing group T1 + T2 from group T3 + T4a. D combined with f provided the highest diagnostic performance (AUC = 0.849) in identifying group N + and group N0 of ESCC.ConclusionsIVIM may be used as an effective functional imaging technique to evaluate preoperative stage of primary tumour and predict presence of lymph node metastases from ESCC.

Tumor Budding: A Novel Prognostic Marker in Breast Carcinoma with Correlation of Histopathological and Immunohistochemical Parameters

Introduction Breast cancer is a highly heterogenous tumor with different subtypes showing varying prognosis. Tumor budding is an unfavorable histological feature of many epithelial cancers. The purpose of this study is to analyze the association between tumor bud density with various histological and immunohistochemical characteristics and to explore its prognostic role in breast carcinoma. Materials and Methods A retrospective analysis was performed on 100 patients of breast cancer diagnosed in our institute from January to December 2017. Hematoxylin and eosin (H&amp;E) stained slides from tumors and immunohistochemical slides were reviewed independently by two pathologists, and clinical data were acquired from computerized records. Patients on neoadjuvant chemotherapy were excluded from the study. Results The study comprised 100 patients of invasive breast carcinoma. The median age was 52 years, and 96% were invasive ductal carcinoma. The median follow-up was 34 months. High tumor bud density was substantially correlated with primary tumor staging (T3, T4; 73% [11/15] cases) and lymph node staging (N2, N3; 68% [13/19] cases) with p-values of 0.017 and 0.023, respectively. Systemic metastasis (85% [6/7] cases) was significantly associated with high tumor bud density (p =0.025) but lymphovascular invasion (LVI) and perineural invasion (PNI) were not significantly associated with tumor bud density (p = 0.762 and 0.862, respectively). Patients with N2 nodal stage had low event-free survival rate than N0/N1 nodal stage irrespective of tumor bud status. Grade 3 tumors with high tumor bud density had worse event-free survival than any other grades. There was no association of tumor bud density with tumor staging, necrosis, PNI, LVI, estrogen receptor (ER), progesterone receptor (PR) and Her2/neu, and event-free survival. Conclusion Strong relationships have been found between tumor bud density and poor prognostic variables such as primary tumor staging and lymph node staging. These results provide credence to the idea that tumor bud density can be an assessable prognostic feature that should be taken into account while reporting breast cancer cases. Tumor bud density evaluation has to be standardized nevertheless if it is to be widely adopted.

Evaluating the role of sarcopenia and [18F]FDG PET/CT parameters in prognosis of pancreatic ductal adenocarcinoma

This study investigates the relationship between 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters, clinicopathological characteristics, and sarcopenia in patients with pancreatic ductal adenocarcinoma (PDAC) and evaluates their prognostic roles. Material and methodsThe primary tumor's maximum standard uptake (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) values, as well as clinicopathological factors, were evaluated retrospectively. Computed tomography (CT) was used to assess the skeletal muscle index (SMI). Sarcopenia was defined based on SMI calculated at the third lumbar vertebra (L3). SMI cut-off values ​​for sarcopenia were accepted as 44.77 cm2/m2 for men and 32.50 cm2/m2 for women. The primary endpoint was the overall survival (OS). OS data were analyzed by the Kaplan-Meier method and compared using the log-rank test. To identify predictive factors for sarcopenia, multivariable logistic regression was used following univariable logistic regression. Cox proportional hazards regression analyses were used to find predictors of OS. ResultsOf the 86 patients included in the study, 37 (43%) were diagnosed with sarcopenia. Compared with non-sarcopenic patients, sarcopenia was observed in older patients (P=0,028) and patients with lower body mass index (BMI) (p=0,001). Age and BMI independently predicted sarcopenia. Univariate analysis identified sarcopenia, advanced stage, and higher primary tumor TLG as significant predictors of overall survival. Multivariate Cox regression analysis revealed that the advanced tumor stage (p=0.017) and higher TLG (p=0,042) independently predicted OS. The median OS was 9.4 months in non-sarcopenic patients and 5.0 months in sarcopenic patients (p=0,021). ConclusionIn this study cohort, advanced-stage disease and higher primary tumor TLG were identified as independent predictors of OS in patients with PDAC. Additionally, we emphasize the importance of incorporating [18F]FDG PET/CT-derived sarcopenia assessments into the prognostic evaluation and clinical management of PDAC patients. While sarcopenia was associated with shorter OS in univariate analysis, it was not an independent predictor in multivariate analysis.

Factors influencing pathological complete response and tumor regression in neoadjuvant radiotherapy and chemotherapy for high-risk breast cancer

BackgroundPathological complete response (pCR) is a well-established prognostic factor in breast cancer treated with neoadjuvant systemic therapy (naST). The determining factors of pCR are known to be intrinsic subtype, proliferation index, grading, clinical tumor and nodal stage as well as type of systemic therapy. The addition of neoadjuvant radiotherapy (naRT) to this paradigm might improve response, freedom from disease, toxicity and cosmetic outcome compared to adjuvant radiotherapy. The factors for pCR and primary tumor regression when neoadjuvant radiation therapy is added to chemotherapy have not been thoroughly described.MethodsWe performed a retrospective analysis of 341 patients (cT1-cT4/cN0-N+) treated with naRT and naST between 1990 and 2003. Patients underwent naRT to the breast and mostly to the supra-/infraclavicular lymph nodes combined with an electron or brachytherapy boost. NaST was given either sequentially or simultaneously to naRT using different regimens. We used the univariate and multivariate regression analysis to estimate the effect of different subgroups and treatment modalities on pCR (ypT0/Tis and ypN0) as well as complete primary tumor response (ypT0/Tis; bpCR) in our cohort. Receiver operating characteristic (ROC) analysis was performed to evaluate the interval between radiotherapy (RT) and resection (Rx) as well as radiotherapy dose.ResultsOut of 341 patients, pCR and pbCR were achieved in 31% and 39%, respectively. pCR rate was influenced by resection type, breast cancer subtype, primary tumor stage and interval from radiation to surgery in the multivariate analysis. Univariate analysis of bpCR showed age, resection type, breast cancer subtype, clinical tumor stage and grading as significant factors. Resection type, subtype and clinical tumor stage remained significant in multivariate analysis. Radiation dose to the tumor and interval from radiation to surgery were not significant factors for pCR. However, when treatment factors were added to the model, a longer interval from radiotherapy to resection was a significant predictor for pCR.ConclusionsThe factors associated with pCR following naST and naRT are similar to known factors after naST alone. Longer interval to surgery might to be associated with higher pCR rates. Dose escalation beyond 60 Gy did not result in higher response rates.

Molecular imaging with 68Ga-PSMA PET/CT in high grade glioma: A biomarker for tumour neo-angiogenesis.

There are several promising radiotracers used for both staging and restaging of primary and recurrent brain tumours based on various mechanisms of tracer localization in tumour cells. 68Ga-PSMA PET has extremely low background uptake in normal brain tissue and consequently high tumour-to-brain ratio making it a promising imaging radiotracer for gliomas. 68Ga-PSMA demonstrates utility in evaluating high grade glioma during both initial workup or when suspecting recurrence. Herein the authors evaluate the role of this imaging modality and the potential future it holds in the management of high grade gliomas.

Evaluation of Applicability of Tumor Budding and Poorly Differentiated Clusters as Additional Prognostic Markers in Colorectal Cancers

Purpose Very few studies have assessed tumor budding (TB) and poorly differentiated cell clusters (PDCs) simultaneously in colorectal cancers (CRCs). The goal of this study was to establish a correlation between these two pertinent histological features and to reinforce the importance of their incorporation in routine histopathological reporting of CRC cases as a means to predict clinical outcome. Methods Resection specimens of colorectal carcinoma were included in the study. Patients who received presurgical therapy, or refused consent were excluded. PDC and TB were evaluated in routine hematoxylin and eosin-stained histopathological sections taken from the advancing edge of the tumor. TB and PDC were reported by selecting a “hotspot” chosen after review of all available slides with invasive tumor. It was then followed by their correlation with other known prognostic factors. Results Spearman's rho calculator for strength of association between TB and PDC as well as association of TB and PDC individually with known prognostic factors revealed statistical significance. Correlation of TB and PDC with histologic grade, primary tumor (pT), and regional lymph node (pN) stage was done based on one-way analysis of variance calculator, which yielded statistically significant results. Conclusion Evaluation of these two histological parameters in the same hotspot field at the tumor invasive front plays a fundamental role in the definition of cancer aggressiveness and prediction of tumor behavior.

PRIORITI: Phase 4 study of triptorelin or active surveillance in high-risk prostate cancer.

To evaluate the efficacy and safety of triptorelin after radical prostatectomy (RP) in patients with negative lymph nodes. PRIORITI (NCT01753297) was a prospective, open-label, randomized, controlled, phase 4 study conducted in China and Russia. Patients with high-risk (Gleason score ≥ 8 and/or pre-RP prostate-specific antigen [PSA] ≥ 20ng/mL and/or primary tumor stage 3a) prostate adenocarcinoma without evidence of lymph node or distant metastases were randomized to receive triptorelin 11.25mg at baseline (≤ 8weeks after RP) and at 3 and 6 months, or active surveillance. The primary endpoint was biochemical relapse-free survival (BRFS), defined as the time from randomization to biochemical relapse (BR; increased PSA>0.2ng/mL). Patients were monitored every 3 months for at least 36 months; the study ended when 61 BRs were observed. The intention-to-treat population comprised 226 patients (mean [standard deviation] age, 65.3 [6.4] years), of whom 109 and 117 were randomized to triptorelin or surveillance, respectively. The median BRFS was not reached. The 25th percentile time to BRFS (95% confidence interval) was 39.1 (29.9-not estimated) months with triptorelin and 30.0 (18.6-42.1) months with surveillance (p=0.16). There was evidence of a lower risk of BR with triptorelin versus surveillance but this was not statistically significant at the 5% level (p=0.10). Chemical castration was maintained at month 9 in 93.9% of patients who had received triptorelin. Overall, triptorelin was well tolerated and had an acceptable safety profile. BRFS was observed to be longer with triptorelin than surveillance, but the difference was not statistically significant.

The Impact of Second Opinion Expert Pathology Review in Patient Management at the Time of Transurethral Resection of the Bladder

Background and objectivePathological features in non–muscle-invasive bladder cancer specimens are pivotal in determining correct patients’ therapeutic management. Sparse data exist regarding the importance of second opinion performed by an expert uropathologist. This study aimed to assess the importance of a second opinion by an expert uropathologist in the management of bladder cancer. MethodsThe study relied on 272 bladder cancer specimens from 231 patients seeking a pathology second opinion after transurethral resection of the bladder for a clinical suspicion of bladder cancer, relapse, or second-look procedure. Pathology second opinion was offered by an experienced fellowship-trained uropathologist. Discrepancies were recorded considering primary tumor staging, the presence of muscularis propria, and the presence of histological variants. Cases were categorized as no significant discordance, major discordance without management change, and major discordance with management change according to the European Urology Association (EAU) guidelines. Key findings and limitationsAmong 272 second opinion cases, 39% (108/272) had major discordance and 28% (75/272) had major discordance with change in management according to the EAU guidelines. Upstaging and downstaging were reported in 66 (24%) patients. Improper identification of the presence of muscularis propria was found in 46 (17%) cases, of which 11 (4%) were deemed clinically relevant. Differences regarding the presence of histological variants were diagnosed in 40 cases (15%), resulting in eight (3%) changes in clinical management. In ten specimens (4%), multiple clinically relevant discrepancies were found. Conclusions and clinical implicationsThe second opinion evaluation changed the clinical management in 25% of the cases. These results support the importance of specimen review by an expert uropathologist as a major driver in the correct bladder cancer management. Patient summaryWe investigated the importance of a second opinion performed by an expert uropathologist in the management of bladder cancer. We found that 25% had their treatment plan changed due to the revised pathological report.

Determinants of pathological complete response and tumor regression in high-risk breast cancer treated with neoadjuvant radiotherapy and chemotherapy.

e12652 Background: Pathological complete response (pCR) is a recognized prognostic indicator in breast cancer patients undergoing neoadjuvant systemic therapy (naST). Known determinants of pCR include intrinsic subtype, proliferation index, grading, clinical tumor and nodal stage, as well as the type of systemic therapy. Incorporating neoadjuvant radiotherapy (naRT) may enhance response rates, disease-free survival, toxicity profiles, and cosmetic outcomes compared to adjuvant radiotherapy. However, the factors influencing pCR and primary tumor regression with the addition of neoadjuvant radiotherapy to chemotherapy are not well-documented. Methods: A retrospective analysis was conducted on 341 patients (cT1-cT4/cN0-N+) who received naRT and neoadjuvant chemotherapy between 1990 and 2003. Treatment included naRT to the breast and, in most cases, to the supra-/infraclavicular lymph nodes, complemented by an electron or brachytherapy boost. NaST was administered either sequentially or concurrently with RT, utilizing various regimens. Univariate and multivariate regression analyses were employed to evaluate the impact of different subgroups and treatment modalities on pCR (ypT0/Tis and ypN0) and complete primary tumor response (ypT0/Tis). Receiver operating characteristic (ROC) analysis assessed the interval between radiotherapy (RT) and surgical resection (Rx), as well as the radiotherapy dose. Results: Out of 341 analyzed patients, 31.1% achieved pCR. Multivariate analysis revealed that pCR rates were affected by the planned type of resection, breast cancer subtype, primary tumor stage, and the interval between radiation and surgery. The biologically effective dose to the tumor did not significantly impact pCR. Univariate analysis identified age, resection type, breast cancer subtype, clinical tumor stage, and grading as significant factors for primary tumor regression. In the multivariate analysis, resection type, subtype, and clinical tumor stage remained significant. Radiation dose to the tumor and the interval from radiation to surgery were not significant for pCR. However, a longer interval from radiotherapy to resection significantly predicted pCR when treatment factors were included in the model. Conclusions: The factors associated with pCR following combined neoadjuvant chemotherapy and radiotherapy are akin to those identified with neoadjuvant chemotherapy alone. A prolonged interval to surgery may be linked to higher pCR rates. Escalating the dose beyond 60 Gy did not lead to increased response rates.

Neoadjuvant immunotherapy (neoIT) in melanoma: A prediction tool for pathological response and recurrence, and the role of adjuvant (Adj) therapy (Tx) to improve recurrence-free survival (RFS).

9579 Background: NeoIT with anti-PD-1 (PD1) showed better event-free survival than adjuvant (adj)IT and is standard of care for pts with stage IIIB–D melanoma. Many pts achieve a Major Pathological Response with neoIT (MPR; complete [pCR] or near-complete [near-pCR] pathological response) and may not require additional Tx; pts with non-MPR (partial [pPR] or no [pNR] pathological response) are at higher risk of recurrence, and may benefit from adj Tx. We sought to: 1) predict pts with non-MPR and at higher risk of recurrence with PD1-based neoIT, and 2) study the role of adjuvant (adj) Tx in pts with pNR. Methods: Pts with stage IIIB–D melanoma treated with PD1-based neoIT were included. Demographics, disease characteristics, baseline blood parameters, radiological response, and clinical outcomes were examined. A multivariate penalized logistic regression model was developed to predict non-MPR and recurrence. Results: Of 184 pts, 30 (16%) had PD1 alone, 107 (58%) had PD1 + anti-CTLA-4 (PD1+IPI), and 47 (26%) had PD1 + novel IT agents. Of the 179 (97%) who underwent surgery, 114 (64%) had MPR (95 [53%] with pCR and 19 [11%] with near-pCR) and 65 (36%) had non-MPR (20 [11%] with pPR and 45 [25%] with pNR). Five pts did not receive surgery (due to clinical progression in 4). The combination of pre-neoIT clinical and pathological features predicted non-MPR pts with an AUC of 0.73. The addition of radiological response (% change from baseline in tumor size: adjusted odds ratio [AOR] 18.94, p=0.0001) to clinical features (pre-neoIT neutrophil [AOR 1.29, p=0.0476] and lymphocyte count [AOR 1.64, p=0.0467], largest lymph node long axis [AOR 1.02, p=0.1056], hemoglobin level [AOR 0.99, p=0.6728], and primary tumor staging [T4 vs. T1; AOR 1.83, p=0.0457]) improved the predictive accuracy (AUC = 0.86). For pts with ≥6 months FU, 2% (2/98) of pts with MPR and 34% (20/58) of pts with non-MPR (20% [4/20] with pPRs and 42% [16/38] with pNR) recurred. Amongst non-MPR pts, the combination of mitotic rate in the primary melanoma (&gt;1 vs. ≤1 mitosis/mm2; AOR 8.23, p&lt;0.0001) and % change from baseline in tumor size (AOR 13.59, p=0.0005) predicted recurrence with an AUC of 0.81. The median % change from baseline in tumor size was +12% in recurrent vs -11% in non-recurrent pts (p=0.0047). Pts with &gt;30% reduction in tumor size did not recur. Of the 38 pts with pNR, the recurrence rate was 64% (7/11) with no adj Tx, 27% (3/11) with adj targeted therapy (TT), and 38% (6/16) with adj PD1. Conclusions: Clinical, pathological, and radiological features can accurately predict MPR or non-MPR to neoIT, as well as recurrence, facilitating response-directed Tx. Acknowledging the small numbers of patients, these early data suggests that Adj TT or PD1 reduces recurrence and should be discussed with pts with pNR. De-escalation of surgery (± adj Tx) should be investigated in MPR pts.

Whole transcriptome analysis to reveal epithelial-mesenchymal transition after neoadjuvant therapy with or without additional anti-EGFR treatment: Subgroup analysis of esophageal squamous cell carcinomas of the SAKK 75/08 and the EORTC AIO POWER study.

4071 Background: In localized disease of esophageal squamous cell cancer (ESCC), a trend in higher pathological response rates and longer time to treatment failure was seen by addition of anti-EGFR treatment to radio-chemotherapy (RCTX) compared to RCTX alone (SAKK 75/08 trial and others). On the contrary, the effect of anti-EGFR treatment to chemotherapy (CTX) remains unclear as no survival benefit was detected within advanced patients (EORTC-AIO-POWER study). Since perfect discrimination and selection of subgroups with highest benefit for anti-EGFR treatment (AB) is missing, we investigated the predictive values of whole transcriptomic gene expression analysis (WTGE) applied on biopsy tissue. Methods: 50 pretherapeutic formalin fixed paraffin embedded specimens of ESCC patients from SAKK 75/08 study were analyzed for the effect of RCTX with and without anti-EGFR AB. As well as 26 historic controls of primary resected tumor stage equally distributed ESCC were analyzed. For the advanced setting, we analyzed 28 additional pretherapeutic biopsies and compared groups from CTX to CTX plus AB. The HTG EdgeSeq method was used for NGS-based WTGE. Response to treatment was assessed by histopathological tumor regression in localized disease and clinical courses. Response to treatment in the advanced tumor setting was assessed to the clinical course of stable disease and partial response versus non-responders. Results: Firstly, NGS-based WTGE failed to show significant differences in expression patterns between responding and non-responding ESCC patients, irrespective of treatment protocols and EGFR AB in the localized as well in advanced disease setting. Secondly however, comparison between pre-treatment biopsies and posttreatment residual tumor tissues detected 781 genes that were upregulated and 623 that were downregulated with gene sets associated with muscle processes and epithelial-mesenchymal transition (EMT) in the localized disease. EMT genes were also enriched in residual tumors after neoadjuvant RCTX compared to primary resection in an independent control cohort. Additionally performed immunohistochemical studies showed lower numbers of ZEB-1 positive ESCC in an independent collection of tumors treated by neoadjuvant RCTX compared to primary resection. Conclusions: Our Whole transcriptomic gene expression analyses suggest that EMT is involved in responses to neoadjuvant protocols including EGFR targeting therapies. Targeting EMT may be a molecular pathway to increase complete responses after neoadjuvant RCTX in ESCC.

Glucopeptide Superstructure Hydrogel Promotes Surgical Wound Healing Following Neoadjuvant Radiotherapy by Producing NO and Anticellular Senescence.

Neoadjuvant radiotherapy, a preoperative intervention regimen for reducing the stage of primary tumors and surgical margins, has gained increasing attention in the past decade. However, radiation-induced skin damage during neoadjuvant radiotherapy exacerbates surgical injury, remarkably increasing the risk of refractory wounds and compromising the therapeutic effects. Radiation impedes wound healing by increasing the production of reactive oxygen species and inducing cell apoptosis and senescence. Here, a self-assembling peptide (R-peptide) and hyaluronic-acid (HA)-based and cordycepin-loaded superstructure hydrogel is prepared for surgical incision healing after neoadjuvant radiotherapy. Results show that i) R-peptide coassembles with HA to form biomimetic fiber bundle microstructure, in which R-peptide drives the assembly of single fiber through π-π stacking and other forces and HA, as a single fiber adhesive, facilitates bunching through electrostatic interactions. ii) The biomimetic superstructure contributes to the adhesion and proliferation of cells in the surgical wound. iii) Aldehyde-modified HA provides dynamic covalent binding sites for cordycepin to achieve responsive release, inhibiting radiation-induced cellular senescence. iv) Arginine in the peptides provides antioxidant capacity and a substrate for the endogenous production of nitric oxide to promote wound healing and angiogenesis of surgical wounds after neoadjuvant radiotherapy.

Enhanced Prognostic Factors for Disease-Free Survival in Penile Squamous Cell Carcinoma: Insights From Songklanagarind Hospital

ObjectiveThis study aimed to investigate disease-free survival (DFS) outcomes and associated prognostic factors among surgically treated penile cancer patients at Songklanagarind Hospital, Thailand, over a 20-year period. MethodsA retrospective analysis was conducted on 208 primary penile cancer patients treated between January 2001 and December 2022. Disease-free survival was assessed using Kaplan-Meier survival curves, and Cox proportional hazard models were employed for multivariate analysis. ResultsAll of patients (100%) were squamous cell carcinoma of penis, with 38.9% having T1 tumors, 70.7% well-differentiated tumors, and 32.6% diagnosed at stage III. The recurrence rate was 16.8%, with a mean time to recurrence of 25.9 months. Disease-free survival rates at 1, 3, and 5 years were 82.1%, 72%, and 70.2%, respectively. Median overall survival was 18.2 months, with rates at 1, 3, and 5 years at 68.7%, 44.7%, and 36.4%, respectively. Significant associations were found between disease-free survival and higher T stage, clinical chronic inflammation, delayed onset of symptoms, primary lesion location, groin node metastasis, lymphovascular invasion, and pelvic lymph node metastases. However, multivariate analysis revealed that higher primary tumor stage (T) was the only independent prognostic factor for disease-free survival. ConclusionThis study provides valuable insights into disease-free survival outcomes in penile cancer treatment at a single institution over an extended period. Higher pathologic T stage emerged as the sole independent prognostic factor for disease-free survival. Further validation through large-scale prospective studies is warranted.

Ribosome-binding protein-1 (RRBP1) expression in prostate carcinomas and its relationship with clinicopathological prognostic factors.

Studies in recent years have shown that ribosome-binding protein-1 (RRBP1) is expressed at high rates in many cancers and that it may be a potential prognostic biomarker. The objective of the present study is to determine the RRBP1 expression level in prostatic carcinoma and neighboring non-neoplastic prostate tissue, the relationship between its expression level with prognostic factors, and the role of RRBP1 in the development of prostate cancer. The study included 45 patients who were diagnosed with prostatic carcinoma and underwent radical prostatectomy in our center between the years 2010 and 2021. Pathology reports were reviewed. Mann-Whitney U test was used for the comparison of RRBP1 and GADPH values of the cases (control and tumoral tissue) between the primary tumor stage (pT) and Gleason score (GS) groups. Hierarchical regression analysis was used to explain the effective variables in explaining the RRBP1 value of the research cases. According to the Mann-Whitney U test, mean and median RRBP1-T values of the cases with GS ≥ 8 were detected to be statistically significantly higher than the mean and median RRBP1-T values of the cases with GS < 8. We found out that RRBP1 was expressed at higher rates in patients with high GS and advanced-stage patients. This result indicated that RRBP1 expression may be important in predicting the prognosis of prostate carcinoma.

Socio-demographic Determinants for Distant Metastases of Breast Cancer

Background: In Bangladesh, breast cancer continues to be the second-most common disease overall (12.5%) and the most prevalent cancer in women (27.4%). Patients with late-stage illness who present in low-income regions with distant metastases have a very poor prognosis. Objective: To determine the socio-demographic variables for breast cancer distant metastases in Bangladeshi women treated at a tertiary level hospital. Materials and Methods: This case control study was done from July 2017 to June, 2018 in National Institute of Cancer Research and Hospital (NICRH), Mohakhali, Dhaka. Results: A total number of 42 patients were taken as cases and another 84 patients without distant metastases were taken as controls. Mean age in case group was 42.67 ±9.27 years and in control group it was 45.13±9.60 years. The majority of the study participants in both the case (33.3%) and control (38.1%) groups had only completed kindergarten. In both the case group (71.5%) and the control group (85.7%), the majority of the women were found to be married. In both categories, the majority of the participants were sedentary workers. Additionally, Table 4 demonstrates that there is no statistically significant difference between the two groups with regard to co-morbidities, a positive family history, cigarette use, type of employment, and the existence of obesity (P &gt; 0.05), stage of primary tumor (p=0.002, OR= 5.81; 95% CI: 1.85 – 18.15). Conclusion: Both the diagnosis and the course of treatment are delayed. Due to their lack of resources and lack of knowledge, many of them did not complete the course of treatment. Additionally, each of these factors contributes to the spread of breast cancer to distant areas.

Ultrasensitive PSA: rethinking post-surgical management for node positive prostate cancer.

Clinicians may offer patients with positive lymph nodes (pN1) and undetectable PSA following surgery for prostate cancer either observation or adjuvant therapy based on AUA, EAU, and NCCN guidelines considering standard PSA detection thresholds of <0.1ng/ml. Here we sought to investigate the outcomes of pN1 patients in the era of ultrasensitive PSA testing. We queried the Northwestern Electronic Data Warehouse for patients with prostate cancer who were pN1 at radical prostatectomy and followed with ultrasensitive PSA. Patients receiving neoadjuvant treatment were excluded. We compared clinical characteristics including age, race, pre-operative PSA, Gleason grade, tumor stage, surgical margins, and nodal specimens to identify factors associated with achievement and maintenance of an undetectable PSA (defined as <0.01 ng/mL). Statistics were performed using t-test, Mann-Whitney U test, chi-squared analysis, and logistic regression with significance defined as p<0.05. From 2018-2023, 188 patients were included. Subsequently, 39 (20.7%) had a PSA decline to undetectable levels (<0.01 ng/mL) post-operatively at a median time of 63 days. Seven percent of these men (3/39) were treated with adjuvant RT + ADT with undetectable PSA levels. 13/39 (33.3%) had eventual rises in PSA to ≥0.01 ng/mL for which they underwent salvage RT with ADT. Overall, 23/39 (59%) patients achieved and maintained undetectable PSA levels without subsequent therapy at median follow-up of 24.2 mo. Compared to patients with PSA persistence after surgery or elevations to detectable levels (≥0.01 ng/mL), patients who achieved and maintained undetectable levels had lower Gleason grades (p=0.03), lower tumor stage (p<0.001), fewer positive margins (p=0.02), and fewer involved lymph nodes (p=0.02). On multivariable analysis, only primary tumor (pT) stage was associated with achieving and maintaining an undetectable PSA; pT3b disease was associated with a 6.6-fold increased chance of developing a detectable PSA (p=0.03). Ultrasensitive PSA can aid initiation of early salvage therapy for lymph node positive patients after radical prostatectomy while avoiding overtreatment in a significant subset. 20% of patients achieved an undetectable PSA and over half of this subset remained undetectable after 2 years.

Long-Term Outcomes of Self-Expandable Metallic Stents as a Bridge to Surgery for Obstructive and Symptomatic Primary Tumors of Stage IV Colorectal Cancer: A Propensity-Score Analysis.

Background: Self-expandable metallic stent (SEMS) was introduced for the treatment of obstructive colorectal cancer (CRC) a few decades ago. However, its long-term outcomes remain controversial, especially for stage IV CRC. The aim of this study was to clarify the outcomes of SEMS as a "bridge to surgery" (BTS) for obstructive and symptomatic primary tumors in stage IV CRC by one-to-one propensity-score matching. Materials and Methods: This retrospective cohort study was conducted at a single center from January 2007 to December 2017. Patients with obstructive and symptomatic primary tumors of stage IV CRC underwent primary resection (PR) or placement of a SEMS as a BTS. They were divided into SEMS and PR groups, and their short- and long-term outcomes were compared. Results: In total, 52 patients were reviewed (SEMS group, 21; PR group, 31). Sixteen patients in both groups were matched using propensity scores. Patients in the SEMS group more frequently underwent laparoscopic surgery than those in the PR group (75% versus 19%, P = .004). The two groups showed no significant differences in perioperative and pathological outcomes. The 5-year overall survival was not significantly different between groups (29% versus 20%, P = .53). Conclusions: As a BTS, the use of SEMS for obstructive and symptomatic primary tumors in CRC stage IV can be a comparable option to PR in terms of short- and long-term outcomes, and would be less invasive with respect to surgical procedures.

Characterization of cerebral radiation necrosis following the treatment of sinonasal malignancies.

Our study aims to determine the incidence and potential risk factors for cerebral radiation necrosis (CRN) following treatment of sinonasal malignancies. One hundred thirty-two patients diagnosed with sinonasal malignancies over an 18-year period were identified at two institutions. Forty-six patients meeting inclusion criteria and treated with radiation therapy were included for analysis. Demographic and clinical-pathologic characteristics were collected and reviewed. Post-treatment magnetic resonance imaging (MRI) at least 1 year following treatment was reviewed to determine presence or absence of CRN. CRN was identified on MRI in 8 of 46 patients (17.4%) following radiation treatment. Patients with a history of reirradiation were more likely to develop CRN (50% vs. 10.5%, p < .05). The BEDs of radiation were also higher in CRN patients compared to non-CRN patients, but this difference was not significant (p > .05). CRN patients had a higher proportion of tumors with skull base involvement than non-CRN patients (100% vs. 57.9%, p = .037). Demographics, comorbidities, pathology, primary tumor subsite, chemotherapy use, and stage of disease demonstrated no significant increase in risk of CRN. Reirradiation and tumor skull base involvement were significant risk factors associated with CRN. Higher average total prescribed and BEDs of radiation were seen in the CRN groups, but these differences were not statistically significant. Gender, comorbidities, tumor subsite, tumor location, and treatment type were not significantly different between groups. Level 3.