Clinicopathological Factors Research Articles

Hispanic/Latino Ethnicity is an Independent Predictor of Worse Survival for Gastric Cancer in a Multicenter Safety-Net Patient Population.

Various population-based studies have shown Hispanic/Latino ethnicity is a risk factor for worse survival in patients with gastric cancer linked to disparate access to care. We aimed to address whether Hispanic patients treated within safety-net hospital systems continue to experience this survival deficit compared to non-Hispanic patients. We performed a retrospective cohort study comparing survival between Hispanic and non-Hispanic patients diagnosed with gastric adenocarcinoma between January 1, 2016 to December 31, 2020 within Los Angeles County's safety-net hospital system. Gastric cancer-specific survival was compared between the two cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model. 448 patients who received care from five medical centers were included. 348 (77.7%) patients self-identified as Hispanic and 100 (22.3%) as non-Hispanic. Mean follow-up time was 2.0 years (median 0.91 years, IQR, 0.34-2.5 years). Hispanic patients were found to be diagnosed at a younger age (55.6 vs 60.7 years, p <0.01), demonstrate higher state area deprivation index (6.4 vs 5.0, p <0.01), and present with metastatic disease (59.8% vs 45%, p =0.04). After adjusting social and oncologic variables, Hispanic ethnicity remained an independent risk factor for worse survival (HR 1.56, [95% CI 1.06-2.28], p = 0.02). Hispanic patients treated within a large, multi-center safety-net hospital system experience worse survival compared to non-Hispanic patients. This suggests ethnic disparities exist within safety-net hospital systems, independent of known clinicopathologic factors. Improving outcomes for Hispanic patients with gastric cancer requires future efforts aimed at defining and addressing these unidentified barriers to care.

Prediction of undetectable circulating tumor DNA by comprehensive genomic profiling assay in metastatic prostate cancer: the SCRUM-Japan MONSTAR SCREEN project.

Undetectable circulating tumor DNA (ctDNA) is an obstacle to performing comprehensive genomic profiling in daily practice to identify genomic alterations. We investigated the associations between clinicopathological factors and undetectable ctDNA using a commercially available comprehensive genomic profiling assay in metastatic prostate cancer. Patients treated with systemic treatment for metastatic prostate cancer were included. ctDNA was analyzed by FoundationOne®Liquid CDx at enrollment. The associations between clinicopathological characteristics and ctDNA detection were analyzed. The number of bone metastasis was associated with ctDNA detection (odds ratio [95% confidence interval], 13.6 [1.71-108], P = 0.014). An algorithm predicting ctDNA detection using clinicopathological parameters was created. If ≥ 4 bone metastases were observed, ctDNA detection was estimated to be 98.9%. Among the patients with < 4 bone metastases, if two or three features among ISUP grade group 5, PSA level ≥ 10ng/ml, and castration resistance were present, the ctDNA detection rate was 96.7% while the ctDNA detection rate was 86.3% if no or only one feature was present. An algorithm created in this study is helpful in determining when to undertake comprehensive genomic profiling assay using blood.

Analysis of clinicopathological characteristics and prognostic factors in 54 metaplastic breast carcinoma patients from northwest China.

Metaplastic breast carcinoma (MBC) is a special type of morphologically heterogeneous and aggressively invasive breast cancer. MBC is characterized by the transformation of tumor epithelium into squamous epithelium and/or mesenchymal components, including differentiation into spindle cells, chondrocytes, and osteocytes. Due to its rarity and invasiveness, there is a paucity of research on MBC prognosis. Furthermore, there are currently no treatment guidelines for MBC. This study analyzed the clinicopathological characteristics, immunophenotype, and prognostic features of MBC. Our aim was to better characterize MBC, thereby identifying potential prognostic factors and new treatment methods. Moreover, we also describe an MBC case treated experimentally with anti-vascular targeted therapy. We retrospectively analyzed clinical pathological data on 54 female patients with MBC from Shaanxi Provincial People's Hospital and the XiJing Hospital of Air Force Medical University. These cases were diagnosed with MBC between January 1st, 2013, and October 1st, 2018. All patients were from the northwest region of China. The gross morphological, histological, and immunohistochemical features of MBC were analyzed. Kaplan-Meier analysis was used to calculate the survival rate, and univariate analysis was performed to identify significant prognostic factors. In addition, the treatment of an MBC patient with anti-angiogenic therapy was described, and a relevant literature review was conducted. MBC was diagnosed in 32 left breasts and 22 right breasts from 54 women aged 21-76 years (median age of 57 years). The maximum tumor diameter ranged from 0.6 to 14 cm (average of 4.1 cm). Of the 54 patients, 47 underwent surgical treatment, with lymph node metastasis found in 17.0% (8/47). According to the World Health Organization classification criteria for breast tumors, the study cohort consisted of 15 cases of squamous cell carcinoma, ten cases of spindle cell carcinoma, nine cases of carcinoma with associated stromal differentiation, 18 cases of mixed carcinoma, and two cases of adenocarcinoma with squamous differentiation. Based on the American Joint Committee on Cancer clinical staging criteria, the patients were classified as Stage I (10 cases, 18.5%), Stage II (26 cases, 48.1%), Stage III (11 cases, 20.4%), and Stage IV (7 cases, 13.0%). Immunohistochemical analysis revealed that 94.4% of patients had triple-negative breast cancer (TNBC), 47 cases showed mutant tumor protein 53 (TP53) expression, 29 cases showed positive epidermal growth factor receptor (EGFR) expression, 43 cases showed positive E-cadherin expression, and 37 cases showed positive Cluster of Differentiation 24 expression. The Ki-67 index ranged from 20% to 90%. Univariate analysis showed that the Ki-67 index was not significantly associated with either progression-free survival (PFS) or overall survival (OS) in MBC patients. Patients with negative axillary lymph nodes had significantly better PFS and OS than those with positive nodes (P < 0.05), and patients with clinical stage I-II disease had better PFS and OS than those with stage III-IV disease (P < 0.05). Patients treated with anthracycline-containing chemotherapy had significantly better PFS than those who did not receive chemotherapy. Univariate analysis revealed that the high expression of EGFR correlated with worse PFS (P < 0.05). The type of surgical approach employed did not affect the prognosis of MBC patients. Following the application of anti-angiogenic therapy, a rapid partial response was observed in an MBC patient with carcinoma and associated stromal differentiation. This patient subsequently underwent surgery and radiation therapy and has now achieved over 6 years of PFS. MBC is a heterogeneous group of tumors with high malignancy and poor prognosis. The large majority is TNBC and exhibits unique immune phenotypes. The poor PFS of MBC patients may be related to EGFR expression, which could become a potential therapeutic target in these patients. Surgery remains the primary treatment method for MBC. The present study found that sentinel lymph node biopsy was feasible in appropriate patients, and that chemotherapy regimens incorporating anthracycline-class drugs did not appear to improve OS. Anti-angiogenic therapy holds promise as a potentially effective treatment approach for MBC, and the optimization of systemic treatment strategies should be a priority in the management of these patients.

Prediction of early clinical response to neoadjuvant chemotherapy in Triple-negative breast cancer: Incorporating Radiomics through breast MRI

This study assessed pretreatment breast MRI coupled with machine learning for predicting early clinical responses to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), focusing on identifying non-responders. A retrospective analysis of 135 TNBC patients (107 responders, 28 non-responders) treated with NAC from January 2015 to October 2022 was conducted. Non-responders were defined according to RECIST guidelines. Data included clinicopathologic factors and clinical MRI findings, with radiomics features from contrast-enhanced T1-weighted images, to train a stacking ensemble of 13 machine learning models. For subgroup analysis, propensity score matching was conducted to adjust for clinical disparities in NAC response. The efficacy of the models was evaluated using the area under the receiver-operating-characteristic curve (AUROC) before and after matching. The model combining clinicopathologic factors and clinical MRI findings achieved an AUROC of 0.752 (95% CI 0.644–0.860) for predicting non-responders, while radiomics-based models showed 0.749 (95% CI 0.614–0.884). An integrated model of radiomics, clinicopathologic factors, and clinical MRI findings reached an AUROC of 0.802 (95% CI 0.699–0.905). After propensity score matching, the hierarchical order of key radiomics features remained consistent. Our study demonstrated the potential of using machine learning models based on pretreatment MRI to non-invasively predict TNBC non-responders to NAC.

Comprehensive analysis of clinicopathological characteristics in oral squamous cell carcinoma arising from oral submucous fibrosis: a retrospective study

BackgroundOral squamous cell carcinoma arising from oral submucous fibrosis is recognized as a clinicopathologically distinct disease. This study aims to summarize and compare the population and clinicopathologic characteristics of OSCC-OSF with other OSCC in Hunan Province, China. The objective is to formulate treatment strategies more in line with regional characteristics.MethodsA retrospective review of OSCC cases recruited from the Second Xiangya Hospital from 2010 to 2020 was conducted. A total of 1,413 OSCC patients were selected, including 481 patients with OSCC-OSF and 932 were other OSCC. Population characteristics, risk factors and clinicopathological manifestations were explored in OSCC-OSF and other OSCC, as well as thinprep cytologic test and DNA quantification.ResultsWe found that OSCC-OSF patients were younger than those with other OSCC. Both types of disease were predominantly observed in males compared to females. Tumor biopsy analysis indicated that tumor cells within OSCC-OSF patients were more likely to be well differentiated and showed a higher frequency of lymph node metastases. Clinicopathological factors, such as the chewing betel nuts habit and smoking, were more prevalent in OSCC-OSF patients in contrast to other OSCC. DNA quantification revealed that the number of DNA aneuploid cells was higher in OSCC-OSF compared to other OSCCs.ConclusionIn this study, OSCC-OSF is considered a clinicopathologically distinct disease. Compared with other OSCC, OSCC-OSF patients have a higher incidence of nodal metastases, an early clinical TNM stage, and a lower three-year survival rate. Therefore, early diagnosis and treatment are crucial to improving the prognosis of OSCC-OSF.

Prognostic determinants in cancer survival: a multidimensional evaluation of clinical and genetic factors across 10 cancer types in the participants of Genomics England’s 100,000 Genomes Project

BackgroundCancer is a complex disease, caused and impacted by a combination of genetic, demographic, clinical, environmental and lifestyle factors. Analysis of cancer characteristics, risk factors, treatment options and the heterogeneity across cancer types has been the focus of medical research for years. The aim of this study is to describe and summarise genetic, clinicopathological, behavioural and demographic characteristics and their differences across ten common cancer types and evaluate their impact on overall survival outcomes.MethodsThis study included data from 9977 patients with bladder, breast, colorectal, endometrial, glioma, leukaemia, lung, ovarian, prostate, and renal cancers. Genetic data collected through the 100,000 Genomes Project was linked with clinical and demographic data provided by the National Cancer Registration and Analysis Service (NCRAS), Hospital Episode Statistics (HES) and Office for National Statistics (ONS). Descriptive and Kaplan Meier survival analyses were performed to visualise similarities and differences across cancer types. Cox proportional hazards regression models were applied to identify statistically significant prognostic factor associations with overall survival.Results161 clinical and 124 genetic factors were evaluated for prognostic association with overall survival. Of these, 116 unique factors were found to have significant prognostic effect for overall survival across ten cancer types when adjusted for age, sex and stage. The findings confirmed prognostic associations with overall survival identified in previous studies in factors such as multimorbidity, tumour mutational burden, and mutations in genes BRAF, CDH1, NF1, NRAS, PIK3CA, PTEN, TP53. The results also identified new prognostic associations with overall survival in factors such as mental health conditions, female health-related conditions, previous hospital encounters and mutations in genes FANCE, FBXW7, GATA3, MSH6, PTPN11, RB1, RNF43.ConclusionThis study provides a comprehensive view of clinicopathological and genetic prognostic factors across different cancer types and draws attention to less commonly known factors which might help produce more precise prognosis and survival estimates. The results from this study contribute to the understanding of cancer disease and could be used by researchers to develop complex prognostic models, which in turn could help predict cancer prognosis more accurately and improve patient outcomes.

Dermatofibrosarcoma Protuberans: An Updated Review of the Literature.

Dermatofibrosarcoma protuberans (DFSP) is a rare proliferative condition representing skin sarcomas which is known to locally recur yet very rarely metastasizes. Its genetic background is a reciprocal translocation t(17;22)(q22;q13) that produces COL1A1-PDGFB gene fusion. Complete resection is the primary treatment. The aim of this review is to outline the pathogenesis, diagnosis, and management of DFSP. A clear-cut distinction between low-to-moderate-grade DFSP with excellent prognosis and high-grade fibrosarcomatous DFSP with a much worse prognosis is underlined. Malignant transformation within DFSP (or high histologic grade), older age, being female, large primary tumor size (≥10 cm), narrow surgical margins of excision (<3 cm), surgical margin positivity for tumor cells, short time to recurrence, numerous recurrences, tumor that was recently rapidly enlarging, and presence of pain in the tumor have all been proposed as clinicopathological risk factors for recurrence and metastasis. A tendency for local growth and local relapses of well- and moderately differentiated DFSPs is an argument for their surgical excision, possibly combined with reconstructive surgery, even in patients of advanced age. Another main point of this review is that cases of DFSP with fibrosarcomatous transformation are a challenge and require careful medical attention. Both anatomopathological evaluation of the presence of lymphovascular space invasion and sentinel lymph node biopsy at DFSP surgery merit further study.

Immunohistochemical Expression of Vitamin D receptor in Breast Cancer in Erbil city

Background &amp; objectives: Vitamin D receptor is a nuclear receptor that modulates the activity of genes. The purpose of this study was to evaluate the frequency of vitamin D receptor expression in breast carcinoma by immunohistochemistry and to investigate the association between vitamin D receptor expression with some clinicopathologic factors, like tumor grading, staging, histologic type (ductal and non-ductal) and the hormonal status. Methods: One hundred formalin-fixed paraffin embedded tissue blocks of mastectomy and core biopsy specimens diagnosed as carcinoma, were obtained from a private laboratory in Erbil city/Iraq from October 2020-October 2022. In this study, vitamin D antibody (a mouse monoclonal antibody) was applied to a breast cancer tissue samples and its expression was assessed. Results: Nuclear vitamin D receptor was expressed in 32% of the cases, and a strong relation was noted between vitamin D receptor expression and low-grade tumor (p = 0.034), estrogen receptor (p-value =0.007), and progesterone receptor (p = 0.045) positivity, while no significant association was noted between vitamin D receptor expression and other clinicopathologic parameters like age, lymph node status, tumor stage, the type of the cancer and human epidermal growth factor receptor 2 status. Conclusion: increased Vitamin D receptor expression in breast tumors appears to be associated with a better prognosis. Vitamin D receptor expressed in one third of cases in which there was significant association with tumor grade and hormonal receptors.

Measurement of changes in serum-based inflammatory indicators to monitor response to nivolumab monotherapy in advanced gastric cancer: a multicenter retrospective study

BackgroundNonresectable gastric cancer develops rapidly; thus, monitoring disease progression especially in patients receiving nivolumab as late-line therapy is important. Biomarkers may facilitate the evaluation of nivolumab treatment response. Herein, we assessed the utility of serum-based inflammatory indicators for evaluating tumor response to nivolumab.MethodsThis multicenter retrospective cohort study included 111 patients treated with nivolumab monotherapy for nonresectable advanced or recurrent gastric cancer from October 2017 to October 2021. We measured changes in the C-reactive protein (CRP)-to-albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) in serum from baseline to after the fourth administration of nivolumab. Furthermore, we calculated the area under the receiver operating characteristic curves (AUC ROCs) for CAR, PLR, and NLR to identify the optimal cutoff values for treatment response. We also investigated the relationship between clinicopathologic factors and disease control (complete response, partial response, and stable disease) using the chi-squared test.ResultsThe overall response rate (complete and partial response) was 11.7%, and the disease control rate was 44.1%. The median overall survival (OS) was 14.0 (95% CI 10.7‒19.2) months, and the median progression-free survival (PFS) was 4.1 (95% CI 3.0‒5.9) months. The AUC ROCs for CAR, PLR, and NLR before nivolumab monotherapy for patients with progressive disease (PD) were 0.574 (95% CI, 0.461‒0.687), 0.528 (95% CI, 0.418‒0.637), and 0.511 (95% CI, 0.401‒0.620), respectively. The values for changes in CAR, PLR, and NLR were 0.766 (95% CI, 0.666‒0.865), 0.707 (95% CI, 0.607‒0.807), and 0.660 (95% CI 0.556‒0.765), respectively. The cutoff values for the treatment response were 3.0, 1.3, and 1.4 for CAR, PLR, and NLR, respectively. The PFS and OS were significantly longer when the treatment response values for changes in CAR, PLR, and NLR were below these cutoff values (CAR: OS, p < 0.0001 and PFS, p < 0.0001; PLR: OS, p = 0.0289 and PFS, p = 0.0302; and NLR: OS, p = 0.0077 and PFS, p = 0.0044).ConclusionsMeasurement of the changes in CAR, PLR, and NLR could provide a simple, prompt, noninvasive method to evaluate response to nivolumab monotherapy.Trial registrationThis study is registered with number K2023006.

Clinicopathological Factors Predicting Pathological Complete Response to Neoadjuvant Anti-HER2 Therapy in HER2-Positive Breast Cancer

Plain Language SummaryNeoadjuvant treatment is the standard approach for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Especially, pathologic response is an important prognostic factor and the adjuvant treatment is dependent on the response. Therefore, predicting the response is important for modulating the treatment sequence, especially in the initial stage of treatment decision. Therefore, we aimed to identify factors that can predict the effectiveness of neoadjuvant chemotherapy, and our results suggest that factors such as tumor size, grade, hormone receptor, and HER2 status should be considered in the treatment of breast cancer.

Evaluation of malignancy in gallbladder tumors using the apparent diffusion coefficient obtained by diffusion‑weighted MRI.

The utility of the apparent diffusion coefficient (ADC) of diffusion-weighted image (DWI) magnetic resonance imaging was examined for evaluating malignancy and prognosis in gallbladder tumors. A total of 63 patients (benign tumors, n=33; cancer, n=30) were included after surgical resection for gallbladder tumors, and their mean ADC values by DWI were obtained. Cases of advanced gallbladder cancer (n=25) were divided into ADCHigh and ADCLow groups, and clinicopathological factors were compared. In 63 cases, ADC values in advanced gallbladder cancer were significantly lower compared with benign tumors and non-advanced gallbladder cancer (P<0.05), and ADC values in early gallbladder cancer were also significantly lower compared with benign tumors (P<0.05). In 25 advanced gallbladder cancer cases, the ADCLow group tended to have a higher rate of advanced stage disease (P=0.09). Disease-free survival and overall survival (OS) of the ADCLow group were worse compared with the ADCHigh group (P<0.01). In the multivariate analysis of OS, poor differentiation and low ADC value were independent prognostic factors. ADC values may be useful for evaluating tumor malignancies in gallbladder tumors.

Molecular subtypes and nomogram for predicting the prognosis of cervical cancer based on a matrix-immune signature

Cervical cancer is a kind of tumor related to chronic HPV infection. Currently, the treatment of cervical cancer is guided mainly by clinicopathological factors. The role of tumor microenvironment in the prognosis and treatment of cervical cancer has been ignored. We aimed to use bioinformatics to identify the molecular subtypes in cervical cancer and construct a predictive nomogram combining a matrix-immune signature (MIS) and clinicopathological factors to support treatment decisions. Two cervical cancer subtypes with different prognoses were identified based on matrix- and immune-genes in TCGA-CESC. The MIS was developed using Cox regression and Lasso algorithm and verified in the Cancer Genome Characterization Initiative (CGCI) using time-dependent receiver operating characteristic (ROC) curve analysis. Multivariable analysis identified lymph node metastases, lymphovascular space invasion, and the MIS as independent prognostic factors, which were used to construct the predictive nomogram. The areas under the ROC curve of the model were 0.872, 0.879, and 0.803 for the 1-, 3-, and 5-year periods, respectively. The C-index was 0.845. Calibration curves confirmed the excellent prognosis prediction of the nomogram. The nomogram indicted a 3-year survival rate of > 90% in patients with a total score > 110.1. The constructed predictive nomogram has significant implications for prognostic assessment and treatment selection in cervical cancer.

CD25+FOXP3+CD45RA− regulatory T-cell infiltration as a prognostic biomarker for endometrial carcinoma

BackgroundRegulatory T (Treg) cells reportedly play crucial roles in tumor angiogenesis as well as antitumor immunity. In order to explore their therapeutic potential, we investigated the precise prognostic impact of Treg markers in endometrial carcinoma.MethodsWe performed multiplexed immunofluorescence and quantitative image analyses of CD25, FOXP3, CTLA4, and CD45RA in tumor specimens from 176 consecutive patients treated at our institution for primary endometrial carcinomas. Bioinformatics analyses were further conducted to corroborate the findings.ResultsHigh CD25+, FOXP3+, and CD25+FOXP3+CD45RA− stromal cell counts correlated with better overall survival (OS) (p = 0.00019, 0.028 and 0.0012) and MSI-high (p = 0.015, 0.016 and 0.047). High CD45RA+ stromal cell count was associated with superficial myometrial invasion (p = 0.0038). Bioinformatics survival analysis by Kaplan-Meier plotter showed that high CD25, FOXP3, CTLA4, and CD45RA mRNA expressions correlated with better OS (p = 0.046, 0.00042, 0.000044, and 0.0022). Univariate and multivariate analyses with various clinicopathologic prognostic factors indicated that high CD25+ or CD25+FOXP3+CD45RA− stromal cell count was significant and independent for favorable OS (p = 0.0053 and 0.0015). We subsequently analyzed the correlations between the multiplexed immunofluorescence results and treatment-free interval (TFI) after primary chemotherapy in recurrent cases, finding no significant associations. Further analysis revealed that high ratio of CD25+ : CD8+ cell count or CD25+FOXP3+CD45RA− : CD8+ cell count correlated with longer TFI (p = 0.021 and 0.021).ConclusionThe current observations suggest that the balance between CD25+ or CD25+FOXP3+CD45RA− cells and CD8+ cells, corresponding to promoting or inhibiting effect on tumor angiogenesis, affect tumor chemosensitivity leading to prognostic significance. CD25+FOXP3+CD45RA− effector Treg tumor infiltration may serve as a useful prognostic biomarker and a potential target for immunotherapeutic manipulation of tumor chemosensitivity by novel management for advanced/recurrent endometrial carcinomas.

Diagnostic value and clinical significance of serum miR-4534 combined with transvaginal color Doppler ultrasound in cervical cancer

AimThe purpose of the present study was to evaluate the diagnostic performance of serum miR-4534 combined with Transvaginal Color Doppler Ultrasound (TVCDS) in cervical cancer patients.MethodsBlood samples from 126 patients with cervical cancer and 83 patients with benign uterine lesions were retrospectively analyzed. Quantitative real time polymerase chain reaction (qRT-PCR) was applied to examine the relative abundances of serum miR-4534 in cervical cancer based on a case–control study. Chi-square test was adopted to analyze the association between serum miR-4534 and other clinicopathological factors. The blood flow of cervix was examined using TVCDS, and the blood flow resistance index (RI) of cervix was summarized. Receiver operating characteristic (ROC) curves were plotted to explore the diagnostic capacity of serum miR-4534 combined with blood flow RI. Logistic regression was employed to analyze the risk factors of cervical cancer.ResultsSerum miR-4534 was distinctly increased in the study group compared with the control group (P < 0.05), while blood flow RI was dramatically decreased (P < 0.05). Moreover, increased miR-4534 was closely associated with lymph node metastasis (P = 0.010), FIGO stage (P = 0.007) and HR-HPV (P = 0.025). ROC curves demonstrated that the area under curve (AUC) of serum miR-4534 combined with the blood flow RI was 0.854, with the sensitivity and specificity of 88.9% and 73.5%, respectively, which displayed a better diagnostic capacity than serum miR-4534 and blood flow RI alone. Logistic regression analysis demonstrated that serum miR-4534 (OR = 8.805, 95% CI = 4.124–18.798; P < 0.001) was a risk factor related to the initiation and formation of cervical cancer, as well as blood flow RI (OR = 0.112; 95% CI = 0.054–0.235; P < 0.001).ConclusionSerum miR-4534 was highly expressed in cervical cancer, and associated with the development and metastasis of cervical cancer patients. MiR-4534 combined with TVCDS exhibited a considerable biomarker to detect cervical cancer patients.

Hyperprogressive disease in patients with advanced cancer treated with immune checkpoint inhibitors.

Hyperprogressive disease (HPD) is a new phenomenon developing in the era of immune checkpoint inhibitor (ICI) therapy. HPD is characterized by an unexpected and fast progression in tumor volume and poor survival. There is no standardized definition for HPD and clinicopathological variables associated with HPD are unclear. Herein, we assessed incidence, treatment outcomes and factors predictive of HPD in patients treated with ICIs. We retrospectively analyzed patients with advanced cancer treated with ICI at one academic center between 2014 and 2021. We used the Lo Russo's adopted criteria combined with clinical and radiologic parameters for the definition of HPD. All patients who underwent their first tumor evaluation according to RECIST1.1 were included. Of 155 patients, 147 were eligible for analysis. The median age was 61 and 83% were male. The cancer types were; lung 67.3%, bladder 12.9%, gastric 9.5%, 5, colon 5.4% and renal cell carcinoma 4.8%. 59.9% of patients were treatment-naive and others had one or more lines of chemotherapy. 19 (12.9%) patients had HPD. In patients who had HPD, progression-free survival (PFS) was significantly shorter (1.5 vs 9.8months, (HR 9.56; 95% CI (5.51-16.57), p < 0.001). The median overall survival (OS) was also shorter for HPD patients than non-HPD (3.0 vs 23.1months, respectively, HR 12.03, 95% CI (6.64-21.81), p < 0.001). Gastric cancer, larger sum of target lesion diameters at baseline, liver metastases, higher LDH level and higher neutrophil-lymphocyte ratio (NLR) were significantly associated with HPD. Our findings demonstrated that HPD was a rapid phenomenon with significantly poor survival rates. Several clinicopathological factors and tumor characteristics might indicate HPD.

Prognostic factors in post-prostatectomy salvage radiotherapy setting with and without hormonotherapy: An individual patient data analysis of randomized trials from ICECaP database

BackgroundEarly salvage radiotherapy (SRT) is the standard of care for biochemical recurrence post-prostatectomy but outcomes are heterogeneous. ObjectiveTo develop a risk scoring system based on relevant standard-of-care clinico-pathological prognostic factors for patients treated with SRT with and without hormonal therapy (HT). Design, setting, and participantsThe Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) database included three randomized trials (Individual patients’ data from 1647 subjects) assessing SRT (GETUG-AFU-16; NRG/RTOG-9601, and a subset of EORTC-22911). Outcome measurements and statistical analysisOutcomes were clinical progression (CP). metastasis free-survival (MFS) and overall survival (OS). Clinico-pathological factors, including pathological Gleason Score (GS), PSA at SRT start, margin status, persistent PSA post-RP and time from RP to SRT were evaluated by multivariable models stratified by type of treatment. Results and limitationsOn multivariable analysis PSA ≥ 0.5 ng/mL at SRT start, GS ≥ 8 and negative margin status were the three strongest prognostic factors. Three prognostic groups defined by number of these risk features (high risk: 2 or 3; intermediate risk: 1 and low risk: 0) were strongly associated with OS, MFS and CP outcomes with SRT alone or with HT. This prognostic group definition was also relevant for patients with persistent PSA post RP and for patients treated < 1 year from RP to SRT and with and without HT. ConclusionA risk score for patients receiving SRT with or without HT, using three standard-of-care clinico-pathological risk factors provides refined prognostic information for individual patient counselling. Patient summaryBy using a composite score of pathology grading (Gleason Score), PSA at start of salvage radiation and margin status data, physicians can provide patients with more refined information on the risk of a second relapse after receiving radiation to the prostate bed after a prostatectomy for a rising or persistent PSA, both with and without hormonal therapy.

Expression of Interleukin-8, Interleukin-12 and Interleukin-13 in Esophageal Squamous Cell Carcinoma: Biomarker Potentiality and Prognostic Significance.

Interleukin-8 (IL8), Interleukin-12 (IL12) and Interleukin-13 (IL13) are cytokines that play regulatory role in cancer pathogenesis. We analysed their expression profile to evaluate as molecular biomarkers of esophageal squamous cell carcinoma (ESCC) and their association with different parameters and patient survival. Expression analysis was performed by Real time quantitative polymerase chain reaction and receiver operating characteristic (ROC) curve analysis was done. The expression profiles were associated with different clinicopathological and dietary factors. Survival and hazard analysis were also performed. IL8 expression showed upregulation in tissue (p = 0.000) and blood samples (p = 0.481), IL12 expression showed downregulation in tissue samples (p = 0.064) and upregulation in blood samples (p = 0.689) and IL13 expression showed upregulation in tissue (p = 0.000) and blood samples (p = 0.006). IL13 expression in tissue showed the highest area under the curve (AUC) value (0.773) for ESCC diagnosis, followed by IL8 expression in tissue (0.704) and IL13 expression in blood (0.643). This study also reveals the correlation of studied cytokines in tissue and blood level. Different clinicopathological and dietary factors showed significant association (p < 0.05) with IL8, IL12 and IL13 expression and with survival of ESCC patients. IL8 expression in blood and IL12 expression in tissue and blood showed significant association (p < 0.05) with patient survival. Altered expression of IL8, IL12 and IL13 may be associated with ESCC progression. Overexpression of IL8 and IL13 in tissue samples may be potential biomarkers for ESCC screening. Additionally, both survival and hazard analysis data indicate the effects of different parameters on the prognosis of ESCC patients.

Prognostic Impact of Tumor Growth Rate During Second-line Chemotherapy in Patients With Gastric Cancer.

Despite the remarkable developments in chemotherapy for gastric cancer (GC), rapid tumor growth is sometimes experienced during chemotherapy. This study investigated the association of tumor growth rate (TGR) during second-line chemotherapy with the prognosis of patients with GC. We retrospectively reviewed 29 patients with GC treated with nab-paclitaxel plus ramucirumab as second-line chemotherapy between 2017 and 2019 at Osaka Metropolitan University. Of them, 13 cases with target lesions were classified into two groups according to TGR using a cutoff value of 0.25. Clinicopathological factors and survival outcomes were compared between the high TGR (n=5) and low TGR (n=8) groups. The median duration of first-line chemotherapy was significantly longer in the high TGR group than in the low TGR group [median 298 days vs. 72.5 days, p=0.030]. Progressive disease (PD) was observed in 60% of patients with high TGR, whereas stable disease (SD) was observed in 75% patients with low TGR. The median survival time (MST) after starting chemotherapy was 488 days in the low TGR group but was not reached in the high TGR group (log rank p=0.215). The MST after PD was 145 days in the low TGR group but was not estimated in the high TGR group (log rank p=0.345). Based on the absence of significant differences in survival outcomes between the high and low TGR groups, sequential late-line chemotherapy might be considered important, even for patients with high TGR.

Extracellular glypican-1 affects tumor progression and prognosis in esophageal cancer.

Cells are covered with a glycan surface layer that is referred to as the glycocalyx (GCX). It has been reported that the formation of the GCX is promoted on cancer cells and is associated with tumor growth and metastasis. Heparan sulfate proteoglycan glypican-1 (GPC1) is a core protein of the GCX that is overexpressed in esophageal squamous cell carcinoma (ESCC) and is involved in the development and progression of cancer cells. The purpose of the present study is to analyze the utility of GPC1 as a new biomarker ralated to glycocalyx that reflects therapeutic effect and prognosis of ESCC. We measured the concentration of GPC1 protein in preoperative plasma from advanced esophageal cancer patients and examined its relationships with clinicopathological factors and therapeutic efficacy, and the effects of extracellular GPC1 were investigated. The following clinical factors were significantly correlated with the preoperative high GPC1 concentration: male, tumor size ≥30 mm, venous invasion, pT factor ≥2, pStage ≥3, residual tumor, and distant metastatic recurrence. Both overall and recurrence-free survival were significantly worse in the high GPC1 group. Extracellular GPC1 protein concentration reflected intracellular GPC1 expression. Furthermore, we examined the effects of extracellular recombinant human (rh)GPC1 on ESCC cells, and found that extracellular rhGPC1 affects cell motility, including migration and invasion. These results demonstrated the utility of extracellular GPC1 as a biomarker, which can be assayed from a less invasive blood sample-based liquid biopsy. Extracellular GPC1 protein plays a role in both tumor cell motility and cancer progression. Thus, plasma GPC1 is a useful biomarker for esophageal cancer progression and may be a potential candidate of therapeutic target.

Impact of Metastatic Lymph Node Ratio on Survival and Prognosis in Rectal Carcinoma: A Retrospective Cohort Study.

Objective This study aimed to evaluate the impact of the metastatic lymph node ratio (mtLNR) on survival outcomes and prognosis in patients with rectal carcinoma, in comparison with other clinicopathological factors. Methods A retrospective cohort analysis was conducted on 97 patients with rectal adenocarcinoma who underwent surgical treatment at Erol Olçok Training and Research Hospital between January 2017 and December 2022. The inclusion criteria consisted of patients over 18 years of age and the absence of hematological disorders or concurrent inflammatory conditions. The patients' demographic data, tumor characteristics, surgical details, lymph node (LN) status, mtLNR, and survival outcomes were analyzed. The optimal cutoff value of mtLNR for predicting mortality was determined using receiver operating characteristic (ROC) curve analysis. Kaplan-Meier survival analysis was employed to estimate overall survival (OS) and disease-free survival (DFS), and differences between groups were evaluated using the log-rank test. The Cox proportional hazards model was used to calculate hazard ratios (HRs) for all-cause mortality. Statistical significance was set at p<0.05. Results The mean age of the patients was 70.31 ± 11.57 years, with 65.98% being male. Low anterior resection (LAR) was performed in 83.51% of the patients, and laparoscopic surgery was conducted in 26.8%. The median OS for the entire cohort was 24 months (range: 3-60). Patients were divided into two groups based on mtLNR, with the cutoff value set at 0.2183. A high mtLNR was significantly associated with poorer DFS and OS (p=0.021 and p=0.003, respectively). Moreover, patients with an mtLNR>0.2183 exhibited significantly higher rates of recurrence, lymphovascular invasion (LVI), and perineural invasion (PNI) compared to those with a lower mtLNR (all p<0.001). The optimal cutoff value of mtLNR predicted mortality with a specificity of 81.4% and a sensitivity of 48.1% (area under the curve (AUC) 0.662, p=0.012). Kaplan-Meier analysis showed a significant difference in survival between the two groups; the risk of all-cause mortality was 3.71 times higher in patients with mtLNR>0.2183 (p=0.002). Conclusion The mtLNR is a strong determinant of survival and prognosis in patients with rectal carcinoma. High mtLNR values are associated with worse survival outcomes and more aggressive tumor characteristics. The findings suggest that mtLNR should be considered in clinical decision-making processes. These results indicate that mtLNR could be a valuable prognostic tool in clinical decision-making.