CD98hc (SLC3A2), a novel biomarker correlating with grade of malignancy in renal cell cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15083-e15083
Author(s):  
Marina Pöttler ◽  
Andrea Aaitel ◽  
Manuela Schmidinger ◽  
Christoph Zielinski ◽  
Gerald Prager
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Tumor Stage ◽  
Prognostic Impact ◽  
Expression Levels ◽  
Tnm System ◽  
Grade Of Malignancy ◽  
Reliable Marker ◽  
Grade 3

e15083 Background: In a variety of malignant diseases certain malignant markers either predict treatment response towards systemic therapies or have a prognostic impact for cancer patients. While a variety of such actionable as well as treatable targets have been characterized, although only in certain cancers, in renal cell cancer (RCC) no prognostic markers have so far been identified. Thus, grading according to the S.A. Fuhrman grading system from 1982 is the only prognostic feature and currently widely considered for treatment assessment. Methods: Paraffin-embedded tumor tissue sections derived from clear cell RCCs were immuno-histochemically analyzed for expression of embryonic transmembrane antigen CD98hc (SLC3A2). Expression levels were semi-quantitative analyzed and results were correlated with grade of differentiation, using the widely accepted Fuhrman classification. Results: We found that grade of malignancy of ccRCCs were directly correlated with high CD98hc expression levels. Semi-quantivative analyses revealed that 0 % (0/2) of grade 1 ccRCC, 70.0 % of grade 2 ccRCC (14/20), 86.6 % of grade 3 (26/30) and 100 % of grade 4 (10/10) were CD98hc positive. (p < 0.01, Qui-Quadrat Pearson test, n = 62). In contrast, tumor stage as determined by the WHO TNM system did not correlate with CD98hc levels (p > 0.05). Conclusions: From these data, we conclude that CD98hc is expressed in RCCs, whereby the extent of expression is likely to correlate directly with grade of malignancy. In ccRCCs, CD98hc might represent a novel and reliable marker for more aggressive and less differentiated subtypes.

scholarly journals Prognostic role of proliferating CD8+ cytotoxic Tcells in human cancers

2021 ◽  
Author(s):  
Niclas C. Blessin ◽  
Wenchao Li ◽  
Tim Mandelkow ◽  
Hannah L. Jansen ◽  
Cheng Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Tumor Stage ◽  
Prognostic Impact ◽  
Tumor Type

Abstract Purpose Expansion of CD8+ cytotoxic Tlymphocytes is a prerequisite for anti-cancer immune activity and has gained interest in the era of immune checkpoint therapy. Methods To understand the CD8+ T cell dynamics in the tumor microenvironment, we used multiplex fluorescence immunohistochemistry to quantitate CD8+ proliferation (Ki67 co-expression) in tissue microarrays from 1107 colorectal, 642 renal cell, 1066 breast, 375 ovarian, 451 pancreatic and 347 gastric cancer samples. Results The density and the percentage of proliferating (Ki67+) CD8+ T cells were both highly variable between tumor types as well as between patients with the same tumor type. Elevated density and percentage of proliferating CD8+ cytotoxic T cells were significantly associated with favorable tumor parameters such as low tumor stage, negative nodal stage (p ≤ 0.0041 each), prolonged overall survival (p ≤ 0.0028 each) and an inflamed immune phenotype (p = 0.0025) in colorectal cancer and, in contrast, linked to high tumor stage, advanced ISUP/Fuhrman/Thoenes grading (each p ≤ 0.003), shorter overall survival (p ≤ 0.0330 each) and an immune inflamed phenotype (p = 0.0094) in renal cell cancer. In breast, ovarian, pancreatic and gastric cancer the role of (Ki67+)CD8+ Tcells was not linked to clinicopathological data. Conclusion Our data demonstrate a tumor type dependent prognostic impact of proliferating (Ki67+)CD8+ Tcells and an inverse impact in colorectal and renal cell cancer.

Lymphopenia and clinical outcome of elderly patients treated with sunitinib for metastatic renal cell cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15615-e15615
Author(s):  
Ugo De Giorgi ◽  
Karim Rihawi ◽  
Michele Aieta ◽  
Giovanni Lo Re ◽  
Teodoro Sava ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Elderly Patients ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Performance Status ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Metastatic Renal Cell Cancer ◽  
Grade 3

e15615 Background: Lymphopenia is associated with toxicity and outcome in several cancer types. We assessed the association of pre-treatment lymphopenia with toxicity and clinical outcome of elderly patients with metastatic renal cell cancer treated with first-line sunitinib. We evaluated the prognostic factors in these patients. Methods: We reviewed the clinical files of 181 patients aged >70 years with mRCC treated with first-line sunitinib in seventeen Italian Oncology Units from February 2006 to September 2011. Baseline lymphopenia was defined as lymphocyte counts <1,000/µL. Results: Twenty–nine patients (16.0%) had a baseline lymphocyte counts <1,000/µL, and 152 (84%) ≥1,000/µL. No difference between the two groups was reported in overall response rate (p = 0.207), dose reductions (p = 0.740); discontinuations due to adverse events (p = 0.175), overall incidence of grade 3-4 toxicities (p = 0.112) even if more patients in the group with lymphopenia had grade 3-4 neutropenia (p = 0.017), grade 3-4 thrombocytopenia (p = 0.017) and grade 3-4 diarrhea (p = 0.006). In multivariate analysis, performance status and Heng score were predictors of progression-free survival (p = 0.015 and p = 0.0006, respectively), while performance status, Heng score, and lymphopenia were found to be significantly associated with overall survival (p = 0.007, p < 0.0001 and p = 0.023, respectively). Conclusions: Sunitinib appeared safe and active in elderly patients with lymphopenia. Lymphocyte counts is an independent prognostic factor for OS in elderly patients with mRCC treated with first-line sunitinib.

An exploratory study to investigate the immunomodulatory activity of radiation therapy in combination with pembrolizumab in patients with renal cell cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16058-e16058
Author(s):  
Jianqing Lin ◽  
Jean H. Hoffman-Censits ◽  
William Kevin Kelly ◽  
Madalina Tuluc ◽  
Colette Shaw ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Radiation Therapy ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Nk Cell ◽  
Cell Cancer ◽  
Single Agent ◽  
Clinical Activity ◽  
Immunomodulatory Activity ◽  
Grade 3

e16058 Background: Preclinical data suggest there are synergistic effects of radiation therapy (RT) and check point inhibitors in anticancer immunity. The primary objective of this study was to explore the immunomodulatory activity of RT alone or in combination with Pembrolizumab (pembro) in solid tumors including renal cell cancer (RCC) patients (pts). Methods: RCC pts who progressed after at least one front-line therapy were eligible. Pts were treated with either RT (8Gy x 1 or 4Gy x 5) followed by (f/b)pembro or 1 dose pembro f/b RT f/b pembro. Pre- and post RT tumor biopsy was obtained to evaluate PD-L1 expression (assay by QualTeck). Immune markers from peripheral blood before, during, and after treatment were analyzed using flow cytometry. Treatment response was measured based on modified RECIST criteria. Results: Twelve RCC patients were enrolled including 2 with non-clear cell subtype. One pt was not evaluable since pt quickly deteriorated and was taken off study. As of January 13, 2017, 2 pts are still on active treatment. Two pts had partial response (18%) and were on study for at 54 and 63 weeks. One responder was treated with 8 Gy f/b pembro while 1 was treated with 1 dose pembro f/b RT f/b pembro. Five pts had stable disease of 18 to 45 weeks and 4 pts (36%, non-responders) had progression in 9 weeks. For adverse events, 1 pt developed grade 3 pneumonitis after 10 cycles of pembro (RT to adrenal mets). Grade 3 AEs include Fatigue, Nausea, Hyperglycemia, Lymphopenia, thrombocytopenia and AST elevation (post RT for liver mets). PDL1 expression and tumor infiltrating lymphocytes presence after RT showed various patterns. Preliminary flow cytometry showed persistent higher numbers of monocytes in non-responders comparing with responders. CD4+, CD8+ and NK cells and other markers are under analyzed and the results will be presented. Conclusions: The combination of RT (8Gy or 20Gy) with pembro is feasible and tolerated, and demonstrates clinical activity. The AE profile is similar to single agent pembro. Monocytes, T and NK cell kinetics are being examined. (ClinicalTrials.gov ID: NCT02318771) Clinical trial information: NCT02318771.

A prospective randomized phase II trial of GM-CSF priming to prevent topotecan-induced neutropenia in chemotherapy-naive patients with malignant melanoma or renal cell carcinoma

Blood ◽  
2001 ◽  
Vol 97 (7) ◽  
pp. 1942-1946 ◽  
Author(s):  
John E. Janik ◽  
Langdon L. Miller ◽  
Edward L. Korn ◽  
Diane Stevens ◽  
Brendan D. Curti ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Phase Ii ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Complete Regression ◽  
Protective Effects ◽  
Gm Csf ◽  
Grade 3 ◽  
To Receive

Abstract We conducted a phase II randomized trial of recombinant granculocyte-macrophage colony-stimulating factor (GM-CSF) administered before topotecan chemotherapy to determine whether it could prevent myelosuppression and to determine the antitumor activity of this topoisomerase I inhibitor in 53 patients with metastatic malignant melanoma and renal cell cancer. All patients received GM-CSF after topotecan at a dose of 250 μg/m2 daily for at least 8 days. Patients randomly assigned to receive GM-CSF priming were treated with GM-CSF at 250 μg/m2 twice daily for 5 days before treatment. Twenty-five patients were randomly assigned to receive GM-CSF priming and 28 to receive topotecan without priming. The primary analysis was restricted to the protective effects seen during the first cycle of therapy. Grade 4 neutropenia occurred in 8 of 23 patients (35%) and grade 3 neutropenia in 5 of 23 patients (22%) randomized to GM-CSF priming, whereas 18 of 26 (69%) and 5 of 26 (19%) patients experienced grade 4 or 3 neutropenia, respectively, without GM-CSF priming (P = .0074). The mean duration of neutropenia was reduced by GM-CSF priming: grade 3 neutropenia from 5.2 ± 0.7 to 2.8 ± 0.7 days (P = .0232) and grade 4 neutropenia from 2.7 ± 0.6 to 1.1 ± 0.4 days (P = 0.0332). The protective effects of GM-CSF extended to the second cycle of treatment. The incidence of febrile neutropenia was also reduced. Chemotherapy-induced anemia and thrombocytopenia were similar in both groups. One partial response was seen in a patient with melanoma, and one patient with renal cell cancer had complete regression of pulmonary metastases and was rendered disease-free by nephrectomy.

Phase II Study of Sorafenib in Patients With Sunitinib-Refractory Metastatic Renal Cell Cancer

2009 ◽  
Vol 27 (27) ◽  
pp. 4469-4474 ◽  
Author(s):  
Giuseppe Di Lorenzo ◽  
Giacomo Cartenì ◽  
Riccardo Autorino ◽  
Gianni Bruni ◽  
Marianna Tudini ◽  
...  
Keyword(s):  
Phase Ii ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Phase Ii Study ◽  
Cell Cancer ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Second Line ◽  
Metastatic Renal Cell Cancer ◽  
Grade 3

Purpose No previous prospective trials have been reported with sorafenib in patients with sunitinib-refractory metastatic renal cell cancer (MRCC). We conducted a multicenter study to determine the activity and tolerability of sorafenib as second-line therapy after sunitinib progression in MRCC. Patients and Methods Between January 2006 and September 2008, 52 patients were enrolled onto this single-arm phase II study. All patients received sorafenib 400 mg orally twice a day until disease progression or intolerable toxicity. The primary end point was objective response rate (complete or partial response) evaluated every 8 weeks by use of the Response Evaluation Criteria in Solid Tumors; secondary end points were toxicity, time to progression (TTP), and overall survival (OS). Results All patients were included in response and safety analyses. Partial responses were observed in 9.6% of patients (five of 52 patients; 95% CI, 5% to 17%) after two cycles. Grade 1 to 2 fatigue, diarrhea, nausea/vomiting, rash, and neutropenia were the most common side effects, noted in 16 (30.8%), 19 (36.5%), 20 (38.5%), 19 (36.5%), and 20 patients (38.5%), respectively. The most common grade 3 toxicity was diarrhea, noted in six patients (11.5%). Median TTP was 16 weeks (range, 8 to 40 weeks), and median OS was 32 weeks (range, 16 to 64 weeks). Conclusion Although well tolerated, sorafenib shows limited efficacy in sunitinib-refractory MRCC. Further randomized trials comparing sorafenib with other drugs that target different biologic pathways are needed to define the best second-line treatment option in these patients.

4F2, a novel marker for grade of malignancy in renal cell cancer (RCC)

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 22148-22148
Author(s):  
M. Pöttler ◽  
Kalinowska ◽  
M. Susani ◽  
A. Haitel ◽  
Zielinski ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Grade Of Malignancy

Randomized phase I/II trial of two schedules of bortezomib and bevacizumab (BBmibmab) in metastatic renal cell cancer: USC trial 4K-05-1.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 574-574
Author(s):  
David I. Quinn ◽  
Denice Wei ◽  
Kristy Massopust ◽  
Charlean Ketchens ◽  
James Hu ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Proteasome Inhibitor ◽  
Clear Cell ◽  
Cell Cancer ◽  
Primary Objective ◽  
Interferon Α ◽  
Baseline Factors ◽  
Grade 3 ◽  
Clinical Trial Information

574 Background: VEGF agents are a mainstay of therapy in advanced RCC. Bev has activity in RCC but was licensed with interferon-α, which can produce side effects and reduced QoL. Based on non-overlapping side effect profiles, we studied bortezomib (Bmib), a proteasome inhibitor, with the VEGF ligand monoclonal antibody, bevacizumab (Bmab). Primary objective was to examine safety/toxicity of 2 dose schedules of Bmib with Bmab with secondary aims of efficacy (benchmarked to NCI data) and correlatives. Methods: From 2005 and 2014, 62 RCC patients with clear cell or papillary predominant histology treated with 0-4 prior therapies were screened: 10 screen failed, 4 were ineligible (2 treated, 2 not) leaving 48 eligible patients, of whom 46 were evaluable for safety and efficacy endpoints with 20 in each of the phase II dose schedules. Regimens were randomly allocated, stratified by MSKCC group. Results: Best tolerated doses of Bmib with Bmab 10mg/kg IV q3wks on each regimen were A: 1.3 mg/m2 on D 1, 4, 8 and 11 q3wks & B: 1.8 mg/m2on days 1 and 8 q3wks. MSKCC strata: low, intermediate, high risk in 43, 42%; 48, 49%; 9, 9% for schedules A and B, respectively; other baseline factors were not significantly different between A & B. Overall: nephrectomy 90%; ECOG 0 73%; male 71%; median age 57 years; Caucasian 48%, Hispanic 33%, Black 8%, Asian 10%;. Median cycles both arms: 5. Best RECIST 1.0 response PR: 13%, 13%; SD 52%, 48%; PD 26%, 35%; Reason off therapy: PD 58, 67%; toxicity 25, 17% in arms A, B. Median OS: 33.4, 14.7 months (p=0.69), TTP 11.2, 9.4 months, PFS 7.3, 6.6 months (p=0.61) in arms A, B. Grade 3+ tox: A 14/24 vs. B 13/24, p=1.0. Arm A had numerically more skin toxicities and grade 2/3 hematological tox (Plats and WBCs) compared to arm B but this was not statistically significant. Conclusions: Randomized comparisons of novel agents are feasible in renal cell cancer using risk factor algorithms. This VEGFrTKI contemporaneous series of Bmab based therapy with 2 schedules of Bmib suggests potential better outcomes for schedule A with more frequent dosing of Bmib – further sensitivity analysis is ongoing to determine whether this is explained by histology or therapeutic sequencing or likely to suggest proteasome as a target in RCC. Clinical trial information: NCT00184015.

scholarly journals The Role of Daily Adaptive Stereotactic MR-Guided Radiotherapy for Renal Cell Cancer

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2763 ◽  
Author(s):  
Shyama U. Tetar ◽  
Omar Bohoudi ◽  
Suresh Senan ◽  
Miguel A. Palacios ◽  
Swie S. Oei ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Survival Rates ◽  
Tumor Diameter ◽  
Safety Margins ◽  
Grade 3 ◽  
Daily Plan ◽  
One Year ◽  
Large Primary

Novel magnetic-resonance-guided radiotherapy (MRgRT) permits real-time soft-tissue visualization, respiratory-gated delivery with minimal safety margins, and time-consuming daily plan re-optimisation. We report on early clinical outcomes of MRgRT and routine plan re-optimization for large primary renal cell cancer (RCC). Thirty-six patients were treated with MRgRT in 40 Gy/5 fractions. Prior to each fraction, re-contouring of tumor and normal organs on a pretreatment MR-scan allowed daily plan re-optimization. Treatment-induced toxicity and radiological responses were scored, which was followed by an offline analysis to evaluate the need for such daily re-optimization in 180 fractions. Mean age and tumor diameter were 78.1 years and 5.6 cm, respectively. All patients completed MRgRT with an average fraction duration of 45 min. Local control (LC) and overall survival rates at one year were 95.2% and 91.2%. No grade ≥3 toxicity was reported. Plans without re-optimization met institutional radiotherapy constraints in 83.9% of 180 fractions. Thus, daily plan re-optimization was required for only a minority of patients, who can be identified upfront by a higher volume of normal organs receiving 25 Gy in baseline plans. In conclusion, stereotactic MRgRT for large primary RCC showed low toxicity and high LC, while daily plan re-optimization was required only in a minority of patients.

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