The prognostic utility of hemoglobin and lymphocytopenia in bladder-sparing therapy.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 370-370
Author(s):  
Michael Drumm ◽  
Hannah Johnson Roberts ◽  
William U. Shipley ◽  
Andrzej Niemierko ◽  
Niall M. Heney ◽  
...  

370 Background: Many patients with bladder cancer are found to have laboratory derrangements such as anemia and lymphocytopenia prior to treatment, though their prognostic value is unknown. We examined pretreatment lab values and clinical outcomes in patients with muscle-invasive bladder cancer (MIBC) who underwent bladder sparing trimodality therapy (TMT). Methods: We performed a retrospective analysis of 181 patients with T2-T4a bladder cancer who underwent TMT between 2001 and 2013. Pretreatment absolute lymphocyte count (ALC), neutrophil to lymphocyte ratio (NLR), and hemoglobin (Hgb) values were collected, and cut-off values were established to be 1.5*10^9/L, 3.12, and 12 g/dl, respectively. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were compared with Kaplan Meier survival probabilities and univariate and multivariate Cox regression analysis, controlling for gender, age, completeness of TURBT, response to TMT, cystectomy, clinical T stage, and hydronephrosis. Results: Median follow-up was 47 months. On univariate analysis, patients with a low pretreatment lymphocyte count had poorer OS (p = 0.03) than patients with a higher pretreatment lymphocyte count (5 year OS rates: 54% and 71%, respectively). Patients with pretreatment anemia had poorer OS (p = 0.001) and DSS (p < 0.001) than patients with a higher pretreatment hemoglobin count, (5 year OS rates: 39% and 65%; 5 year DSS rates: 39% and 72%, respectively). On multivariate analysis, pretreatment anemia was significantly associated with poorer OS (HR 2.58, 95% CI 1.36–4.90) and DSS (HR 3.23, 95% CI 1.62–6.43), whereas complete response to TMT was significantly associated with improved OS (HR 0.24, 95% CI 0.13–0.43) and DSS (HR 0.29, 95% CI 0.14–0.59). Complete response to TMT was significantly associated with improved DFS (HR 0.36, 95% CI 0.21–0.61), and a higher clinical T stage was associated with poorer DFS (HR 2.38, 95% CI 1.19–4.75). Conclusions: When adjusting for clinical factors, pretreatment anemia remained an independent predictor of overall and disease-specific survival following TMT. Further prospective validation of lab values and clinical outcomes in MIBC are needed.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 513-513 ◽  
Author(s):  
David Tomoaki Miyamoto ◽  
Ewan Gibb ◽  
Kent William Mouw ◽  
Yang Liu ◽  
Chin-Lee Wu ◽  
...  

513 Background: Trimodality therapy with TURBT followed by chemoradiation is an acceptable alternative to cystectomy for muscle invasive bladder cancer (MIBC). Genomic profiling has demonstrated MIBC can be divided into molecular subtypes with differing responses to chemotherapy. We explored the utility of genomic data to select patients for bladder-sparing trimodality therapy. Methods: Transcriptome wide gene expression profiles were generated for 189 MIBC TURBT samples from patients treated with trimodality therapy at a single institution. Of these, 103 passed microarray QC. Molecular subtype and expression of bladder cancer genes were assessed for association with overall and disease-specific survival. Transcriptome wide differential expression analysis was used to explore gene set enrichment in trimodality therapy response groups. Results: The chemoradiation cohort (n = 103) had a median followup of 6.9 years for alive patients, and was classified into four subtypes: basal (n = 44), basal claudin-low (n = 12), infiltrated luminal (n = 17) and luminal tumors (n = 30). There was no significant difference in overall or disease-specific survival by subtype. However, higher expression of the luminal-associated PPARG was correlated with increased survival after adjusting for subtype and clinical factors (HR = 0.52, p = 0.002). In contrast, a p53 signature predicted worse survival after adjusting for clinical factors (HR = 1.92, p = 0.022). Elevated mRNA expression of the DNA damage repair gene MRE11 was associated with improved survival in the trimodality cohort (HR = 0.69, P = 0.031), consistent with its potential role as a predictive biomarker for radiation response. Gene set enrichment revealed differential regulation of immune pathways in trimodality therapy responders relative to non-responders, including enrichment of interferon gamma signaling (p = 0.01) and CXCL9 (p = 0.031), suggestive of an interplay between tumor immunologic microenvironment and response to chemoradiation. Conclusions: Transcriptional profiling of MIBC revealed gene signatures correlated with response to chemoradiation, suggesting the potential of genomics to guide use of trimodality therapy.


2020 ◽  
Author(s):  
muyuan liu ◽  
Litian Tong ◽  
Manbin Xu ◽  
Xiang Xu ◽  
Bin Liang ◽  
...  

Abstract Background: Due to the low incidence of mucoepidermoid carcinoma, there lacks sufficient studies for determining optimal treatment and predicting prognosis. The purpose of this study was to develop prognostic nomograms, to predict overall survival and disease-specific survival (DSS) of oral and oropharyngeal mucoepidermoid carcinoma patients, using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database. Methods: Clinicopathological and follow-up data of patients diagnosed with oral and oropharyngeal mucoepidermoid carcinoma between 2004 and 2017 were collected from the SEER database. The Kaplan-Meier method with the log-rank test was employed to identify single prognostic factors. Multivariate Cox regression was utilized to identify independent prognostic factors. C-index, area under the ROC curve (AUC) and calibration curves were used to assess performance of the prognostic nomograms. Results: A total of 1230 patients with oral and oropharyngeal mucoepidermoid carcinoma were enrolled in the present study. After multivariate Cox regression analysis, age, sex, tumor subsite, T stage, N stage, M stage, grade and surgery were identified as independent prognostic factors for overall survival. T stage, N stage, M stage, grade and surgery were identified as independent prognostic factors for disease-specific survival. Nomograms were constructed to predict the overall survival and disease-specific survival based on the independent prognostic factors. The fitted nomograms possessed excellent prediction accuracy, with a C-index of 0.899 for OS prediction and 0.893 for DSS prediction. Internal validation by computing the bootstrap calibration plots, using the validation set, indicated excellent performance by the nomograms. Conclusion: The prognostic nomograms developed, based on individual clinicopathological characteristics, in the present study, accurately predicted the overall survival and disease-specific survival of patients with oral and oropharyngeal mucoepidermoid carcinoma.


2019 ◽  
Author(s):  
A. Font ◽  
M. Domènech ◽  
R. Benítez ◽  
M. Rava ◽  
M. Marqués ◽  
...  

ABSTRACTPlatinum-based neoadjuvant chemotherapy (NAC) increases the survival of patients with organ-confined urothelial bladder cancer (UBC). Because not all patients benefit from treatment, NAC has not been widely applied in the clinical setting. There is strong evidence, based on retrospective studies, that patients with Basal/Squamous (BASQ)-like tumours present with more advanced disease and have worse prognosis; global transcriptomics can identify tumour subtypes associated with response to NAC. We aimed to investigate whether tumour immunohistochemical (IHC) subtyping predicts NAC response. Patients with muscle-invasive UBC having received platinum-based NAC were identified in two hospitals in Spain. Tissue microarrays were constructed; RNA and DNA were extracted from full sections. Nanostring analysis and immunohistochemistry to identify BASQ-like tumours and mutational analysis of UBC oncogenes. We used hierarchical clustering to classify 126 tumours and adjusted logistic regression to assess association with treatment response. Outcomes were progression-free survival and disease-specific survival; univariable and multivariate Cox regression models were applied. We found very high concordance between mRNA and protein for the 4 markers analyzed. We identified three main subgroups: BASQ-like (FOXA1/GATA3 low; KRT5/6/14 high), Luminal-like (FOXA1/GATA3 high; KRT5/6/14 low), and mixed-cluster (FOXA1/GATA3 high; KRT5/6 high; KRT14 low). Patients with BASQ-like tumours were more likely to achieve a pathological response to NAC, displaying a disease-specific survival similar to that of the remaining patients. In conclusion, patients with BASQ-like tumours - identified through simple and robust immunohistochemistry - have a higher likelihood of undergoing a pathological complete response to NAC. Prospective validation in independent series is required.Novelty and impactNeoadjuvant chemotherapy is an important component of the management of patietns with muscle-invasive bladder cancer but improved stratification is necessary. This retrospective study shows that patients with BASQ-like tumors can be identified using immunohistochemistry on paraffin-embedded tissue and are 4-fold more likely to achieve a pathological complete response to platinum-based NAC. The disease-specific survival of patients with BASQ-like tumours treated with NAC was not different from that of other tumour subtypes.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 123-123
Author(s):  
Sylvie Lorenzen ◽  
Nils Homann ◽  
Salah-Eddin Al-Batran ◽  
Florian Lordick ◽  
Tibor Schuster ◽  
...  

123 Background: The aim of this study was to evaluate the impact of pathologic complete response (pCR) on outcome in patients with gastric or esophagogastric junction (EGJ) adenocarcinoma after treatment with preoperative docetaxel/platin /fluoropyrimidine based chemotherapy. Methods: This analysis of a prospective database identified patients who received at least one cycle of preoperative docetaxel/platin/fluoropyrimidine-based chemotherapy for at least T3/4 and N+ disease. An association of pretreatment clinicopathologic factors and pCR was investigated. Overall survival, disease-free survival and disease-specific survival were analyzed according to the achievement of a pCR. Results: A total of 120 patients received preoperative docetaxel-based chemotherapy and underwent subsequent resection of the primary tumor. 15 pts (13%) had distant metastases (M1) at initial diagnosis. 18 patients achieved a pCR in the primary (15%). Median follow-up was 41.1months. The median DFS and OS for the whole population was 24.1 and 48.6 months, respectively. DFS was significantly prolonged in pCR compared to non-pCR patients (HR 2.65, 95% CI 1.1- to 6.2; 3-year DFS probability: 71.8%±10.7 and 37.7%±5.1, respectively, P-value log-rank test=0.018). For patients with a pCR the median DFS was not reached and for those without pCR the median DFS was 22.1 months. Patients with a pCR showed an almost 50% decreased risk of death compared to non-pCR patients (HR 0.53; 95%CI 0.23 to 1.23; P=0.131). Disease-specific survival (DSS) was significantly longer in pCR vs. non-pCR patients (HR 0.188, 95%CI 0.046-to 0.77; P= 0.021). Two clinicopathological parameters were identified as predictors of pCR: tumor localization in the EGJ (p=0.019) and intestinal tumor type according to Laurén’s classification (p=0.042). Conclusions: The analysis confirms that pCR to neoadjuvant chemotherapy is a predictor of favourable patient outcome in patients with gastric or EGJ adenocarcinoma. Tumor location in the EGJ and intestinal histology represent factors significantly associated with the achievement of pCR.


2010 ◽  
Vol 25 (2) ◽  
pp. 87-92 ◽  
Author(s):  
Alexander W. Eckert ◽  
Andreas Schütze ◽  
Matthias H.W. Lautner ◽  
Helge Taubert ◽  
Johannes Schubert ◽  
...  

The critical molecular regulator of hypoxia is the hypoxia-inducible factor 1 alpha (HIF-1α). The prognostic impact of this regulator protein in oral squamous cell carcinomas (OSCC) has not been comprehensively investigated. The aim of this study was to analyze the expression of HIF-1α in 82 patients with OSCC and to correlate it with their disease-specific survival. Immunohistochemical staining for HIF-1α was performed on 82 OSCC specimens using a standard immunoperoxidase technique. The expression of HIF-1α was correlated with poor disease-specific survival for OSCC patients. Patients with negatively or weakly HIF-1α–expressing tumors had a survival rate of 80%, whereas the survival decreased to only 33.6% in case of moderate or strong expression. In multivariate Cox regression analysis, we found a 3.5-fold increased risk of tumor-related death when HIF-1α was strongly expressed (p=0.016) compared to negative or weak expression of HIF-1α. We suggest HIF-1α is an independent prognostic marker in OSCC. Immunohistochemical detection of HIF-1α appears to be useful in the diagnosis of OSCC and to provide prognostic information in addition to TNM stage and histological grade.


2014 ◽  
Vol 86 (2) ◽  
pp. 158 ◽  
Author(s):  
Orcun Celik ◽  
Hakan Turk ◽  
Salih Budak ◽  
Yusuf Ozlem Ilbey

Malignant fibrous histocytoma (MFH) is the most common soft tissue sarcoma in adults. Urinary tract is a very rare location for MFH. Involvement of the bladder is more common in males and at the 6th decade of life. A case of MFH of the bladder with poor prognosis is presented. Prognostic factors for MFH are tumor grade, amount of invasion, age, tumor size, and histological type. Survival rate is very low and 3-year disease specific survival is approximately 40%.


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