MP14-04 PREOPERATIVE TUMOR MEASUREMENTS ARE INDEPENDENTLY PREDICTIVE OF OVERALL SURVIVAL FOLLOWING CYTOREDUCTIVE NEPHRECTOMY

652 Background: Studies suggest that overall survival (OS) following cytoreductive nephrectomy (CN) is associated with preoperative tumor measurements including primary tumor diameter, number of metastatic sites, sum of metastatic tumor diameters and primary tumor percent of overall burden. Current risk models, however, do not account for tumor burden. This study evaluated associations between OS and preoperative tumor measurements for patients treated with CN during the targeted therapy era. Methods: Data for consecutive mRCC patients treated with CN at 4 institutions from 2006-2017 were analyzed after determining IMDC risk category, primary tumor (PT) diameter, number of metastatic sites, sum of metastatic tumor diameters and PT percentage of overall burden. Univariate and multivariable (MV) Cox models evaluated tumor measurement and IMDC risk associations with OS. Results: A total of 617 patients were available for analysis. Median PT diameter was 10.0 cm (IQR 7-13cm), number of metastatic sites was 2 (IQR 1-2), sum of metastatic tumor diameters was 4.5 cm (IQR 2-10cm) and PT percent of overall burden was 73.7% (IQR 60-85%). After univariate analysis, all 4 tumor burden measures were associated with OS (p≤0.001 for all). MV models evaluating IMDC risk category with individual tumor burden measurements demonstrated that all measures were predictive as continuous variables: PT diameter (HR 1.03, 95% CI 1.01-1.06, p=0.007), sum of metastatic tumor diameters (HR 1.04, 95% CI 1.02-1.05, p<0.001), PT percent of overall burden (HR 0.43, 95% CI 0.27-0.68, p<0.001), and number of metastatic sites (HR 1.52, 95% CI 1.25-1.85, p<0.001). Additional MV models were created using clinically significant tumor measurement cutoffs and IMDC risk groups. OS was independently associated with IMDC intermediate (HR 3.17, 95% CI 1.84-5.44, p<0.001) and poor risk (HR 3.85, 95% CI 2.21-6.70, p<0.001), PT percentage of overall burden <90% (HR 1.41, 95% CI 1.05-1.89, p=0.021), and >2 metastatic sites (HR 1.60, 95% CI 1.29-2.00, p<0.001). Conclusions: PT and metastatic disease burden are independently associated with OS following CN. Future risk models should include tumor burden measurements.

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208 E7777 (denileukin diftitox) enhances anti-tumor activity and significantly extends survival benefit of anti-PD-1 in syngeneic solid tumor models

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0208 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A224-A225

Author(s):

Mary Woodall-Jappe ◽

A Raghav Chari ◽

Anil Namboodiripad ◽

Chandrasekhar Goda

Keyword(s):

Overall Survival ◽

Tumor Growth ◽

Solid Tumor ◽

Therapeutic Benefit ◽

Tumor Models ◽

Treg Depletion ◽

Immune Biomarkers ◽

Group 5 ◽

Tumor Measurements ◽

Anti Tumor Activity

BackgroundRegulatory T cell (Tregs) inhibit activity of anti-tumor T cells, and have been shown to limit checkpoint inhibitor effectiveness. Depletion of Tregs seems desirable during immunotherapy, but chronic Treg depletion with antibody therapies can lead to serious autoimmune adverse events. Compared to antibodies, the fusion protein E7777 (IL-2/diphtheria toxin) has a relatively short half-life in circulation, which allows for transient and selective Treg depletion. The potential therapeutic benefit of combining E7777 with anti-PD-1 was tested in syngeneic solid tumor models.MethodsCT26 colon and H22 liver cancer tumors were implanted subcutaneously in immunocompetent BALB/c mice. E7777 (2.5 mcg/mouse, i.v.) was given on a Q7Dx3 schedule. Anti-murine PD-1 was given (100 mcg/mouse, i.v.) Q4Dx5. Groups of 16 mice received each agent as monotherapy or in combinations. Sequencing of combination administration was also varied: Group 4 started treatment on the same day; Group 5 received E7777 2 days prior to start of anti-PD-1; Group 6 received anti-PD-1 first. Tumor growth was compared across all groups. In survival studies, mice were treated for 3 weeks and observed with twice weekly tumor measurements. In other experiments, tumors, tumor-draining lymph nodes, and spleens were examined by IHC and by flow cytometry of immune cells from dissociated tissues at defined points, for immune biomarkers.ResultsFigure 1 shows additive benefit from the E7777 + anti-PD-1 combinations over either monotherapy. Most importantly, figure 2 and table 1 show significantly enhanced overall survival from a 3 week course of combinations compared to either agent alone (p<0.005) or to vehicle controls (p<0.000001). There was no clear distinction among different sequencing regimens. Benefit correlated with enhanced CD8:Treg ratios in tumors.Abstract 208 Figure 1Tumor growth in s.c. syngeneic solid tumors. N=16/groupAbstract 208 Figure 2Overall survival in s.c. syngeneic models. N=16/groupAbstract 208 Table 1Calculated median survivalConclusionsDepletion of Tregs by E7777 significantly increased anti-tumor activity and durably extended overall survival compared to treatment with anti-PD-1 alone in syngeneic solid tumor models. Clinical studies of a combination of the two agents are planned.Ethics ApprovalAll studies were conducted at Crown Bio, and were approved by the Crown Bio IACUC.

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Nephrectomy Followed by Interferon Alfa-2b Compared With Interferon Alfa-2b Alone for Metastatic Renal Cell Cancer

50 Studies Every Urologist Should Know ◽

10.1093/med/9780190655341.003.0020 ◽

2021 ◽

pp. 113-118

Author(s):

Christopher Weight

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell Cancer ◽

Renal Cell ◽

Performance Status ◽

Cell Cancer ◽

Interferon Alfa ◽

Cytoreductive Nephrectomy

This chapter summarizes the findings of a landmark trial of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma performed in the interferon era. All enrolled patients had a good performance status. It found overall survival extended by about 3 months in the cytoreductive-nephrectomy-plus-interferon arm versus the interferon-only arm.

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Cytoreductive Nephrectomy and Overall Survival of Patients with Metastatic Renal Cell Carcinoma Treated with Targeted Therapy—Data from the National Renis Registry

Cancers ◽

10.3390/cancers12102911 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2911

Author(s):

Alexandr Poprach ◽

Milos Holanek ◽

Renata Chloupkova ◽

Radek Lakomy ◽

Michal Stanik ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Locally Advanced ◽

Treatment Algorithm ◽

Progression Free Survival ◽

Cancer Center ◽

Cytoreductive Nephrectomy

The role of cytoreductive nephrectomy (CN) in treatment of locally advanced or metastatic renal cell carcinoma (mRCC) in the era of targeted therapies (TT) is still not clearly defined. The study population consisted of 730 patients with synchronous mRCC. The RenIS (Renal carcinoma Information System) registry was used as the data source. The CN/TT cohort included patients having CN within 3 months from the mRCC diagnosis and subsequently being treated with TT, while the TT cohort included patients receiving TT upfront. Median progression-free survival from the first intervention was 6.7 months in the TT arm and 9.3 months in the CN/TT patients (p < 0.001). Median overall survival was 14.2 and 27.2 months, respectively (p < 0.001). Liver metastasis, high-grade tumor, absence of CN, non-clear cell histology, and MSKCC (Memorial Sloan-Kettering Cancer Center) poor prognosis status were associated with adverse treatment outcomes. According to the results of this retrospective study, patients who underwent CN and subsequently were treated with TT had better outcomes compared to patients treated with upfront TT. The results of the study support the use of CN in the treatment algorithm for mRCC.

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What is the added value of actual tumor measurements (TM) in predicting overall survival (OS)? The North Central Cancer Treatment Group (NCCTG) findings

Journal of Clinical Oncology ◽

10.1200/jco.2008.26.15_suppl.6520 ◽

2008 ◽

Vol 26 (15_suppl) ◽

pp. 6520-6520 ◽

Cited By ~ 1

Author(s):

M. E. Campbell ◽

S. J. Mandrekar ◽

S. L. Hillman ◽

R. M. Goldberg ◽

A. A. Adjei ◽

...

Keyword(s):

Overall Survival ◽

Treatment Group ◽

Cancer Treatment ◽

Added Value ◽

North Central ◽

The North ◽

Tumor Measurements

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Expectations for overall survival in mRCC patients who were selected for upfront cytoreductive nephrectomy in the targeted therapy era.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.646 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 646-646

Author(s):

E. Jason Abel ◽

Jose A. Karam ◽

Philippe E. Spiess ◽

Jay D. Raman ◽

Wade J. Sexton ◽

...

Keyword(s):

Overall Survival ◽

Targeted Therapy ◽

Risk Category ◽

Cytoreductive Nephrectomy ◽

Cox Models ◽

Poor Risk ◽

Percentage Survival ◽

Co Morbidity ◽

Risk Patients

646 Background: Surgical selection is critical to obtain the best outcomes for mRCC patients treated with cytoreductive nephrectomy (CN). Prior studies suggest that international metastatic disease consortium (IMDC) poor risk patients should not be considered for upfront CN because of expectation for short overall survival (OS). The purpose of this study is to evaluate OS among IMDC risk categories for patients treated with upfront cytoreductive nephrectomy during the targeted therapy era at five independent institutions. Methods: After IRB approval, data for consecutive mRCC patients treated with CN at 5 institutions from 2006-2017 was analyzed. Kaplan-Meier method was used to estimate survival from date of surgery and univariate/multivariable Cox models were used to evaluate associations with OS. Results: Of 1163 patients who were treated with CN at 5 institutions, 914 (79%) patients were treated without neoadjuvant systemic therapies. Preoperative IMDC risk category for upfront CN patients was favorable in 71 (8%), intermediate in 598 (65%), and poor in 245 (27%) patients. Median age was 61 (53-68) and median Charlson co-morbidity index was 1 (0-2). Median (IQR) patient follow-up for patients alive at last follow-up was 42.7 months (23, 69). The median OS (IQR) following upfront nephrectomy was 115.4 months (33,NR) for favorable risk patients, 28.6 months (9-65) for intermediate risk patients and 21.8 months (10-47) for poor risk patients. No differences were identified in OS among 5 different institutions (p=0.11) Of 245 poor risk patients, OS was not associated with co-morbidity status or age were not associated with OS (p=0.77, 0.92). Percentage survival at 1, 2, 3 and 5 years was 69%, 48%, 34%, and 20% in the poor risk cohort. Conclusions: Conclusions: After stratification by the IMDC model, observed survival following upfront cytoreductive nephrectomy in this multi-institutional cohort was longer than expected from prior studies, which may be partially attributed to surgical selection bias.

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Prognostic value of simple blood biomarkers of systemic inflammation for metastatic renal cell carcinoma (mRCC) patients who undergo cytoreductive nephrectomy (CNx).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.350 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 350-350

Author(s):

Jigi Moudgil-Joshi ◽

Mark Stares ◽

Alex Laird ◽

Steve Leung ◽

Jahangeer Malik ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Multivariate Analysis ◽

Inflammatory Response ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Systemic Therapy ◽

Renal Cell ◽

Cytoreductive Nephrectomy

350 Background: The role of cytoreductive nephrectomy (CNx) in patients with metastatic renal cell carcinoma (mRCC) is currently in question. Assessing the benefits and risks of CNx is challenging, with a lack of validated prognostic tools. Biomarkers of the systemic inflammatory response have prognostic utility in mRCC and are included in the IMDC score used to predict survival in patients with mRCC treated with systemic therapy. We sought to investigate their role in patients with mRCC who had undergone CNx. Methods: A cohort of 68 patients, suitable for first-line VEGFR inhibitor (VEGFRi) systemic therapy, who had undergone CNx for mRCC, were identified from a clinical database of patients referred to a regional mRCC service. Inflammatory biomarkers from routine blood tests (haemoglobin, white cell count, neutrophil count, platelets, C-reactive protein (CRP), albumin) and the IMDC score, measured at the time of diagnosis of mRCC, were recorded. The relationship between these and overall survival and time to VEGFRi (tVEGFRi) was examined using Kaplan-Meier and Cox-regression methods. Results: Data were available for 68 patients. Median survival was 33.7 months. On multivariate analysis, albumin ( < 35g g/dL v ≥35 g/dL) and CRP (≤ 10 mg/L v > 10 mg/L) were independently associated with overall survival (p = 0.027 and p = 0.034 respectively). Albumin stratified survival from 24.7 to 87.2 months (p < 0.0001) and CRP from 29.4 to 82.3 months (p = 0.004). 40 (59%) patients subsequently commenced VEGFRi therapy. Median tVEGFRi was 18.1 months, with only 5 (7%) patients commencing treatment within 3 months. 16 (24%) patients yet to receive systemic therapy remain alive after a median 54.0 months follow-up. On multivariate analysis, albumin was also predictive of tVEGFRi (p = 0.037), stratifying tVEGFRi from 6.07 to 45.7 months (p = 0.002). Conclusions: These results highlight that biomarkers of the systemic inflammatory response are strong prognostic factors in mRCC patients who have undergone CNx. Albumin and CRP, but not IMDC, predict survival in this patient group. Significantly, the population investigated here differ from those included in the CARMENA and SURTIME studies, with a majority undergoing surveillance prior to VEGFRi therapy. Our results support a role for CNx in patients where deferred systemic therapy strategies may be employed. Albumin may assist in clinical decision making when considering when to start systemic therapy. We advocate further studies to investigate the prognostic role of these simple, routine clinical tests in patients with mRCC undergoing CNx.

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