CD73 expression in primary and metastatic renal cell carcinoma (RCC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 643-643 ◽  
Author(s):  
Abhishek Tripathi ◽  
Sarah E Johnston ◽  
Yan D Zhao ◽  
Oudai Hassan ◽  
Linda F Thompson ◽  
...  

643 Background: Agents targeting the PD-1 pathway have improved outcomes in RCC. CD73 may be an additional mechanism which tumors can exploit for immune evasion. It is regulated by hypoxia inducible factor (HIF) and converts AMP to adenosine. The resulting increase in extracellular adenosine can inhibit T-cell effector function. We evaluated CD73 expression in primary and metastatic tumor samples in patients with RCC. Methods: A commercial TMA (US Biomax) consisting of 31 primary clear cell RCC samples (2 with sarcomatoid features) with 8 matched and 1 unmatched metastases was used to assess CD73 expression. A genitourinary pathologist (OH) confirmed pathology and grade. Immunohistochemistry (IHC) was performed using a monoclonal anti-CD73 antibody (Cell Signaling; D7F9A). A combined score (CS: % of cells positive x intensity) was employed to quantify CD73 expression. Expression levels between matched primary and metastatic tissue was compared using Wilcoxon signed-rank test. Correlation of CD73 expression (CS > 0) in primary tumor with baseline clinical and pathologic characteristics was assessed using Kruskal-Wallis and Fisher's exact tests. Overall survival (OS) was estimated using the Kaplan-Meier method. Comparison between CD73 expression groups used log rank test. Results: CD73 expression was seen in 19% (n = 6) of primary and 66.7% (n = 6) of metastatic samples. Among matched primary and metastatic samples (n = 8 each), median CS was 25 (Q1-Q3:0-105) in metastatic samples while none of the corresponding primary samples demonstrated CD73 expression (median CS = 0, p = 0.062). CD73 expression in primary tumor samples did not correlate with baseline clinical or pathologic features. Five-year OS was 50% in patients who expressed CD73 in primary tumors compared to 84% in those who did not (p = 0.26). Conclusions: We observed a numerical increase in CD73 expression in metastatic tissue compared to primary RCC samples and worse 5 year OS. The small number of samples has limited statistical significance. Further studies are needed to examine the impact of CD73 expression on outcomes in RCC patients treated with currently approved checkpoint inhibitors and the investigational CD73 antagonists that are in early phases of development.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 299-299 ◽  
Author(s):  
M. Salem ◽  
S. N. Shah ◽  
L. S. Wood ◽  
P. Elson ◽  
A. Medsinge ◽  
...  

299 Background: The impact of neoadjuvant sunitinib on CE-CT parameters and nephrometry score of primary RCC tumors remains unknown. Methods: Retrospective review of baseline and prenephrectomy CE-CT from a prospective phase II trial of neoadjuvant sunitinib (50 mg sunitinib continuous dosing) in unresectable primary RCC tumors with or without metastatic disease. CE-CT parameters and R.E.N.A.L. nephrometry score for each lesion were determined in pts who underwent subsequent surgery. RECIST and MASS criteria were used to assess primary tumor radiographic response. CT changes were analyzed using the sign test and Wilcoxon signed rank test. Results: Twenty nine pts were enrolled, of which 13 pts (85%M; median age 63y) underwent post-sunitinib resection of 16 primary tumors (3 pts had multifocal RCC). Post-therapy, 88% of tumors had decreased long diameter (median 32% decrease, p<0.001 vs. baseline), 88% decreased attenuation (median 30 HU reduction, p=0.006) and 69% increased necrosis (p=0.001). 56% of tumors had a decrease in nephrometry score (median 1 point decrease; 10 to 9, p=004). At baseline, 81% of tumors were highly complex by nephrometry score; following therapy 46% of the highly complex tumors became moderately complex. At baseline 13 tumors abutted renal hilar vital structures, whereas following treatment 4 tumors demonstrated abutment. Adenopathy decreased (range, 23%-83%) in 4/4 patients with enlarged baseline lymph nodes, with complete resolution in 1 patient. RECIST objective response was seen in 38% and SD in 56% of primary tumors; 1 tumor had PD based on size despite > 95% necrosis. MASS criteria response was favorable 38%, intermediate 62%. Two of four pts had reduction in extent of venous thrombus (1 pt from level 0 to resolved and 1 pt from level IV to II). Conclusions: Neoadjuvant sunitinib resulted in decreased size/attenuation, increased necrosis of the primary tumor and reduction in lymphadenopathy and venous thrombus in pts who underwent subsequent surgery. Sunitinib reduced the RENAL nephrometry score and facilitated nephrectomy, notably due to impact on tumor proximity to vital structures in the renal hilum. [Table: see text]


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhangheng Huang ◽  
Xin Zhou ◽  
Yuexin Tong ◽  
Lujian Zhu ◽  
Ruhan Zhao ◽  
...  

Abstract Background The role of surgery for the primary tumor in breast cancer patients with bone metastases (BM) remains unclear. The purpose of this study was to determine the impact of surgery for the primary tumor in breast cancer patients with BM and to develop prognostic nomograms to predict the overall survival (OS) of breast cancer patients with BM. Methods A total of 3956 breast cancer patients with BM from the Surveillance, Epidemiology, and End Results database between 2010 and 2016 were included. Propensity score matching (PSM) was used to eliminate the bias between the surgery and non-surgery groups. The Kaplan-Meier analysis and the log-rank test were performed to compare the OS between two groups. Cox proportional risk regression models were used to identify independent prognostic factors. Two nomograms were constructed for predicting the OS of patients in the surgery and non-surgery groups, respectively. In addition, calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the performance of nomograms. Result The survival analysis showed that the surgery of the primary tumor significantly improved the OS for breast cancer patients with BM. Based on independent prognostic factors, separate nomograms were constructed for the surgery and non-surgery groups. The calibration and ROC curves of these nomograms indicated that both two models have high predictive accuracy, with the area under the curve values ≥0.700 on both the training and validation cohorts. Moreover, DCA showed that nomograms have strong clinical utility. Based on the results of the X-tile analysis, all patients were classified in the low-risk-of-death subgroup had a better prognosis. Conclusion The surgery of the primary tumor may provide survival benefits for breast cancer patients with BM. Furthermore, these prognostic nomograms we constructed may be used as a tool to accurately assess the long-term prognosis of patients and help clinicians to develop individualized treatment strategies.


2000 ◽  
Vol 124 (4) ◽  
pp. 526-530 ◽  
Author(s):  
K. Y. Lam ◽  
Victor Tang

Abstract Objective.—The clinicopathologic features of splenic metastases have seldom been investigated. The aim of this study was to evaluate the clinical and pathological impact of splenic metastases. Case Material.—We reviewed the clinical/autopsy records and pathologic features of 92 Chinese patients (58 men, 34 women) with secondary nonlymphoid splenic tumors recorded during a 25-year period. Results.—The incidence of splenic secondary tumors at autopsy was 0.6% and at splenectomy, 1.1%. The lesions were often seen in elderly patients (mean age, 60 years). Seven (8%) of the splenic lesions were symptomatic. The symptomatic splenic lesions, as compared with asymptomatic lesions, were bigger and were found more often in women and younger patients. Two patients experienced spontaneous splenic rupture because of metastatic carcinoma. Eighty-seven (95%) of the secondary splenic tumors were carcinomas. Lung was the most common primary tumor site (21%), followed by the stomach (16%), pancreas (12%), liver (9%), and colon (9%). Rarely reported sources of primary tumor, such as esophageal carcinomas, nasopharyngeal carcinoma, and choriocarcinoma, were also found. Splenic metastases could be identified macroscopically in 74 (80%) of our patients. Grossly, splenic metastases involved the splenic capsule (n = 8) or were solitary (n = 31), multiple (n = 30), or diffuse (n = 8) lesions in the splenic parenchyma. Isolated splenic metastases were noted in 5.3% of the metastases found at autopsy. Many of the metastatic lesions in the spleen were identified shortly after primary tumors were detected (mean latent period, 6.7 months). The time from diagnosis of the primary tumor to metastasis to the spleen was more than 2 years in 14 patients. Conclusions.—Splenic metastases are uncommon. A variety of clinical and pathologic patterns were noted in our series.


1995 ◽  
Vol 13 (8) ◽  
pp. 2094-2103 ◽  
Author(s):  
J L Abbruzzese ◽  
M C Abbruzzese ◽  
R Lenzi ◽  
K R Hess ◽  
M N Raber

PURPOSE Diagnostic strategies designed to identify the underlying primary malignancies in patients with unknown primary tumors (UPTs) have relied on retrospective analyses. We analyzed 879 consecutive patients referred with suspected UPTs to determine the yield and cost of a limited diagnostic evaluation, assess the contribution of specific studies to diagnosis, and analyze the survival patterns of patients in whom the primary tumor was diagnosed. PATIENTS AND METHODS Data from patients with a suspected UPT were entered into a computerized data base, and the patients underwent a predefined limited diagnostic evaluation. Primary malignancies were diagnosed by pathologic review alone or by pathologic criteria plus a physical or radiographic finding. Survival was measured from diagnosis, estimated using the Kaplan-Meier method, and compared using the Cox-Mantel log-rank test. RESULTS A primary tumor was found in 179 of 879 patients (20%). The survival duration of patients in whom the primary tumor was diagnosed was superior to that of patients in whom the primary tumor remained unknown. Specific patient subsets contributed most to the improved survival duration of the group in which the primary tumor was found, including lymphoma patients diagnosed solely by pathologic criteria and female patients with primary breast or ovarian cancer. The cost of diagnosis was mostly due to the extensive use of computed tomography. Except for ovarian cancer, computed tomography rarely identified treatable primary tumors. CONCLUSION The limited diagnostic evaluation used in this study identified patients with treatable malignancies and increased the survival duration of a population of suspected UPT patients. Primary malignancies with the best survival can be diagnosed through careful pathologic review and focused evaluations for breast and ovarian cancer in women.


2020 ◽  
Vol 8 (2) ◽  
pp. e000532
Author(s):  
Bruno Alicke ◽  
Klara Totpal ◽  
Jill M Schartner ◽  
Amy M Berkley ◽  
Sophie M Lehar ◽  
...  

The recent success of multiple immunomodulating drugs in oncology highlights the potential of relieving immunosuppression by directly engaging the immune system in the tumor bed to target cancer cells. Durable responses to immune checkpoint inhibitors experienced by some patients may be indicative of the formation of a T cell memory response. This has prompted the search for preclinical evidence of therapy-induced long-term immunity as part of the evaluation of novel therapeutics. A common preclinical method used to document long-term immunity is the use of tumor rechallenge experiments in which tumor growth is assessed in mice that have previously rejected tumors in response to therapy. Failure of rechallenge engraftment, typically alongside successful engraftment of the same tumor in naive animals as a control, is often presented as evidence of therapy-induced tumor immunity. Here, we present evidence that formation of tumor immunity often develops independent of therapy. We observed elevated rates of rechallenge rejection following surgical resection of primary tumors for four of five commonly used models and that such postexcision immunity could be adoptively transferred to treatment-naïve mice. We also show that tumor-specific cytolytic T cells are induced on primary tumor challenge independent of therapeutic intervention. Taken together these data call into question the utility of tumor rechallenge studies and the use of naïve animals as controls to demonstrate therapy-induced formation of long-term tumor immunity.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1109-1109
Author(s):  
Deborah L White ◽  
Verity A Saunders ◽  
Thea Kalebic ◽  
Timothy P Hughes

Abstract We have previously demonstrated significant interpatient variability in the IC50imatinib, a measure of the intrinsic sensitivity of a patient to imatinib induced kinase inhibition. Furthermore, this measure is predictive of the achievement of major molecular response (MMR &gt; 3 log reduction in BCR-ABL) in de-novo CML patients treated with imatinib (n=60)1. In an expanded patient pool (n=116) we now perform an evaluation of the IC50 as a predictor of response, and address the IC50imatinib as a guide to dose selection. Samples were obtained with informed consent from de novo CML patients enrolled to either the TIDEL (600mg imatinib) or TOPS (randomised 400mg vs 800mg imatinib) trials. Blood was collected pre therapy, and the IC50 was performed as previously1. Outcome data was assessed using Kaplan Meier Analysis and the log rank test was used to assess statistical significance. In our previous analysis the IC50imatinib was divided about the median value for the cohort (0.6μM) into low and high IC50, with a significantly greater proportion of patients with low IC50imatinib achieving MMR by 12 months. In this expanded patient pool, we confirm this finding (&lt;median of 0.7μM for this patient group) (low IC50 65% of patients achieve MMR by 12 mo vs high IC50 39% of patients p=0.014) Dividing the IC50’s into quartiles we now demonstrate that the IC50imatinib is a continuous variable with a greater proportion of patients in the lower quartile achieving MMR than those in the higher (Table 1 Total). Addressing the issue of dose we demonstrate that no patients with IC50&gt;0.95uM achieve MMR on 400mg, and that this is statistically significantly when compared to all other groups. At 600mg while there is no overall significant difference there is a statistically relevant difference between groups 1, 2 and 4 as indicated. In contrast, at 800 mg the effect of IC50imatinib is overcome. MMR by 12 months Total 400mg 600mg 800mg p value Group1 &lt;0.5μM 67% (27) 83% (12)* 50% (8)* 86% (7) 0.470 Group 2 &gt;0.5&lt;0.7μM 63% (30) 67% (6)* 53% (17)* 71% (7) 0.337 Group 3 &gt;0.7&lt;0.95μM 45% (31) 40%(5)* 30% (10) 56% (16) 0.139 Group 4&gt;0.95μM 32% (28) 0% (7)* 22% (9)* 58% (12) 0.016 P value 0.042 0.018 0.108 0.778 Table 1: Dividing the patients into quartile based on the IC50 imatinib and assessing the Impact of dose on the achievement of MMR by 12 month. *p value &lt;0.05 between groups (n). The failure to achieve a Complete Cytogenetic Response by 12 months is considered a suboptimal response. Assessing the molecular equivalent (≥2 log reduction in BCR-ABL) we demonstrate that a significantly greater proportion of patients with IC50imatinib&gt;0.7μM fail to achieve a 2 log reduction when treated with 400mg (IC50 &lt;0.7μM 11%: &gt;0.7μM 33% p=0.034), and 600mg (IC50 &lt;0.7μM 12%: &gt;0.7μM 22% p=0.036). However, there is no significant difference in the 800mg patient cohort (IC50 &lt;0.7μM 7%: &gt;0.7μM 14% p=0.79). This analysis confirms that the IC50imatinib, is predictive of imatinib response. Patients with an IC50imatinib &lt;0.7μM are likely to respond well to doses of 400mg imatinib, as suggested by evaluation of statistically relevant outcome benefit. In contrast patients with higher IC50imatinib (&gt;0.7μM) may benefit from higher dosing regimens (p=0.012). Thus, the accurate assessment of IC50imatinib could support dose optimization strategy for patients with a suboptimal response.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17543-e17543
Author(s):  
S. Ahmed ◽  
M. M. Mirza ◽  
A. Farooq ◽  
L. Kronish ◽  
M. Jahanzeb ◽  
...  

e17543 Background: TNBC is associated with a worse prognosis than luminal subtypes. There is discordance among studies assessing the impact of race on outcomes of TNBC. Our objective was to assess whether African American (AA) vs. Caucasian (CA) race predicted survival outcomes for women with TNBC treated at a single institution in Memphis, TN. Secondary objectives were to examine the association of race with patient and tumor characteristics. Methods: Patients with stage I-III TNBC were identified from our breast cancer database and confirmed by review of pathology reports. Event free survival (EFS) was measured from the date of surgery to the date of first recurrence (locoregional, distant, or contralateral), death from breast cancer or last follow-up. Breast cancer specific survival (BCSS) was measured from the date of surgery to the date of death from breast cancer or last follow-up. Fisher's exact test was used for association between variables, Kaplan Meier method for survival estimates, and log rank test for survival comparison between groups (p < 0.05: significant). Cox proportional hazards models with patient, tumor and treatment variables were fitted for EFS and BCSS. Results: Of the 105 patients with TNBC, 71% were AA. There was no significant association between race and stage at diagnosis (p = 0.68). 71% of AA women were < 55 years old and 43% were pre-menopausal vs. 50% and 23% of CA women respectively. There was a trend towards association of race with age and menopausal status (p = 0.08). Ninety three percent of the patients received neo/adjuvant chemotherapy. With a median follow up of 26 months, 26% of AA vs. 20% of CA women had an event (p = 0.62). Overall 3 year EFS and BCSS estimates were 69% and 82% respectively. Racial differences in EFS and BCSS for AA vs. CA (65% vs. 80% and 78% vs. 89%, respectively) did not achieve statistical significance (log rank p = 0.22 for EFS and 0.26 for BCSS). Race was not a significant predictor of EFS or BCSS on uni-variable or multi-variable analysis. Stage at diagnosis retained significance for EFS and BCSS on uni-variable and multi-variable testing. Conclusions: Race did not affect outcomes in our cohort of TNBC patients treated similarly. The high event rate underscores the poor prognosis of TNBC and the need for more effective therapies. No significant financial relationships to disclose.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 629-629
Author(s):  
Andrea Fontana ◽  
Giacomo Allegrini ◽  
Mazhar al Zoubi ◽  
Paola Collecchi ◽  
Chiara Mazzanti ◽  
...  

629 Background: Currently, no biomarkers of trastuzumab (T) clinical resistance have been validated. The aim of this pilot study was to evaluate the impact of PIK3CA mutations and p95HER2 (pHER2 truncated form) expression on the efficacy of a T based-therapy in a HER2-positive metastatic breast cancer (MBC) patients (pts). Methods: 107 HER2-positive MBC pts, treated in the last 10 years, were evaluated. Median age was 54 years (25-79); ECOG performance status was 0 in 56% of pts; all pts received several lines of treatment including T; biomarkers molecular analysis was performed in 70 tumor specimens. The IHC expression of p95HER2 was evaluated by a monoclonal antibody that specifically recognizes only the HER2 external domain; the HER2 integrity was defined by the presence of a homogeneous membrane staining (moderate or intense) in at least 30% of the cells, otherwise the HER2 was defined as p95HER2 positive. PIK3CA mutations in exons 9 and 20 were detected by automated sequencing. The molecular data were correlated to Time to progression (TTP) of the first line treatment including T and the Overall Survival (OS) by using the Kaplan-Meir method and the log-rank-test. Results: p95HER2 positive pts and PIK3CA mutations in exon 9 or 20 were detected in 42% and 22% of tumor specimens, respectively. p95HER2 positive tumors showed a shorter TTP and OS that did not reach statistical significance; PIK3CA mutations correlated with a worse TTP (median 7,6 vs 11,3 months) and OS (median 20,1 vs 41,0 months, p= 0,046). Conclusions: These preliminary results suggest a possible role of PIK3CA mutational status in predicting the outcome of MBC pts treated with T.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3590-3590 ◽  
Author(s):  
Hagen F. Kennecke ◽  
Jason Yu ◽  
Sharlene Gill ◽  
Winson Y. Cheung ◽  
Charles Davic Blanke ◽  
...  

3590 Background: In 2009, pts with M1 colorectal cancer were divided into two subsets for the American Joint Committee on Cancer (AJCC) 7th edition. Pts with metastases (mets) confined to one organ or site at initial diagnosis became stage M1a while multiple sites or peritoneal mets became M1b. The objectives of the study are to evaluate the impact of site of mets and M1a/b staging among pts with M1 colorectal cancer. Methods: All pts referred to the BC Cancer Agency from 1999-2007 with newly diagnosed M1 colon or rectal cancer were included. Demographic, treatment, and outcome data were prospectively collected. The prognostic impact of individual sites of mets was assessed by hazard ratio estimates from univariate Cox models. Multivariable Cox proportional-hazards models were used to determine variables associated with overall survival in the entire cohort and in those undergoing resection of their primary tumor. Results: 2,049 pts with M1 disease were included. Median age was 66 years; 71% had colonic origin; 70% had their primary tumor resected; and 69% received chemotherapy. In univariate analysis, solitary mets were associated with improved survival. In multivariable analysis, M1a/b status still had significant prognostic effect. The effect remained significant in the subgroup analysis of pts with resected primary tumors when histology, T and N stage were included. Conclusions: Pts with solitary mets, including peritoneum, have superior overall survival as compared to those with multiple sites of mets. AJCC 7th edition staging that includes M1a/b provides significant prognostic information and should be considered in clinical practice and trials of pts with M1 disease who otherwise have few prognostic factors. [Table: see text]


Author(s):  
Sally Hewat ◽  
Joanne Walters ◽  
Monica Lee

Despite the cultural and linguistic diversity of the Australian population, research suggests that speech pathologists do not feel confident when providing services to Cultural and Linguistic Diversity (CALD) clients and would benefit from further education and training in this area. Cultural empathy has been described as a precursor to cultural competence and previous research has demonstrated the positive impact on nursing students’ cultural empathy toward CALD clients following an interactive cultural simulation experience. This study investigated the feasibility and effectiveness of an online cultural simulation activity in developing the cultural empathy of speech pathology students. Students completed an online cultural simulation in their own time, followed by a tutorial debrief. Both the simulation and debrief were considered to comprise the ‘simulation activity’; which was a component of a first-year introduction to clinical practice course. Participants completed a pre-survey and post-survey, containing the Comprehensive Empathy Scale (CES) and demographic questions. Results were analysed using the Wilcoxon Signed Rank test and a Paired Sample t-test, and a power analysis was conducted to direct future studies. Ten students participated and improved an average of 11.3 on the CES (p=0.14). A power analysis revealed that a minimum of 45 participants would be needed in future studies to observe any statistically significant results. The online application of the cultural simulation activity was feasible, and results indicate an improvement in cultural empathy, although the improvement did not reach statistical significance. Implications for future studies are discussed.


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