MP61-07 HIGH RISK DISEASE AND POOR FOLLOWUP: THE ROLE OF RENAL MASS BIOPSY IN A VA COHORT

Aims: Renal mass biopsy (RMB) is advocated to improve management of small renal masses, however there is concern about its clinical utility. This study aimed to elicit opinions about the role of RMB in small renal mass management from surgeons managing renal cell carcinomas (RCC), and examine the frequency of pre-treatment biopsy in those with RCC. Methods: All surgeons in two Australian states (Queensland: n = 59 and Victoria: n = 108) who performed nephrectomies for RCC in 2012/2013 were sent questionnaires to ascertain views about RMB. Response rates were 54% for Queensland surgeons and 38% for Victorian surgeons. We used medical records data from RCC patients to determine RMB frequency. Results: Most Queensland (81%) and Victorian (59%) surgeons indicated they rarely requested RMB; however 34% of Victorians reported often requesting RMB, compared with no Queensland surgeons. This was consistent with medical records data: 17.6% of Victorian patients with T1a tumours received RMB versus 6.7% of Queensland patients ( p < 0.001). Surgeons’ principal concerns regarding RMB related to sampling reliability (90%) and/or histopathological interpretation (76%). Conclusions: Most surgeons report infrequent use of RMB for small renal masses, however we observed practice variation. The principal reasons for infrequent use were concerns about sampling reliability and histopathological interpretation, which may be valid in regions with less access to interventional radiologists and uropathologists. Further evidence is required to define patient groups for whom biopsy results will alter management. Level of evidence: Not applicable for this multicentre audit.

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Kidney Cancer Research Network of Canada (KCRNC) consensus statement on the role of renal mass biopsy in the management of kidney cancer

Canadian Urological Association Journal ◽

10.5489/cuaj.6176 ◽

2019 ◽

Vol 13 (12) ◽

Author(s):

Ranjena Maloni ◽

Luke T. Lavallée ◽

Kristen McAlpine ◽

Anil Kapoor ◽

Frédéric Pouliot ◽

...

Keyword(s):

Cancer Research ◽

Kidney Cancer ◽

Renal Mass ◽

Consensus Statement ◽

Research Network ◽

Cancer Research Network ◽

Renal Mass Biopsy

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Oncogenic Predictors of Outcome in Older AML Patients Treated Intensively. Analysis of the ALFA-1200 Trial

Blood ◽

10.1182/blood-2018-99-111144 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 993-993 ◽

Cited By ~ 1

Author(s):

Raphael Itzykson ◽

Elise Fournier ◽

Thorsten Braun ◽

Céline Berthon ◽

Alice Marceau-Renaut ◽

...

Keyword(s):

High Risk ◽

Univariate Analysis ◽

Gene Mutations ◽

Penalized Regression ◽

Low Risk ◽

Tp53 Mutations ◽

High Risk Disease ◽

Clinical Covariates ◽

Wbc Count

Abstract Context. The prognostic value of gene mutations in older AML patients (pts) treated intensively remains unclear. Only one study has explored the role of mutation patterns determined by NGS in older AML pts prospectively treated with various chemotherapies in years 2000-2010 (Eisfeld Leukemia 2018). Methods. Pts older than 60y enrolled in the ALFA-1200 trial (NCT01966497) between 09/2012 and 06/2016 were sequenced with a 37-gene myeloid panel. Pts received one 7+3 course followed by 2 intermediate-dose cytarabine courses. Pts with non-favorable risk were eligible for allogeneic stem cell transplantation (SCT). Variable selection for multivariate analyses was performed by lasso penalized regression including age, gender and log(WBC) as covariates. Results. Sequencing was done in 471 (93%) of the 509 enrolled pts. Median age and WBC count were 68y and 5.3x109/L, respectively (resp). CR (including CRp) was achieved in 341 (72%) pts and 90 underwent RIC-SCT in first CR. With a median follow-up of 25.4 months, median OS was 20.7 months. Pts had a median of 3 mutations (range 1-10). The 17 mostly frequently mutated genes (≥5% of pts, by decreasing frequency: DNMT3A, NPM1, TET2, ASXL1, FLT3, SRSF2, IDH2, RUNX1, NRAS, IDH1, STAG2, BCOR, TP53, PTPN11, U2AF1, EZH2 and KRAS) were retained for prognostic analyses. Genes belonging to a common pathway (eg. NRAS and KRAS) may have divergent prognostic values, preventing biology-informed grouping of mutations. Cytogenetic risk (derived from ELN 2017, Döhner Blood 2017, not considering gene mutations) was favorable (fav), intermediate (int), adverse (adv) and missing in 3%, 72%, 18% and 7% resp. Because of the few pts with fav cytogenetics in our cohort, pts were further grouped into non-adv and adv cytogenetics. CR rates and median OS were 75.6% vs 56.6% and 24.8 vs 9.5 months in pts with non-adv and adv cytogenetics, resp (both p<0.0001). Because of difference in mutational patterns and gene-gene interactions, the prognostic role of mutations was considered independently in these two non-adv and adv subgroups. In the 388 pts with non-adv cytogenetics, NPM1 mutations independently predicted improved CR rate (Odds Ratio [OR]=2.3, p=0.014), while mutations in ASXL1 (OR=0.46, p=0.012), RUNX1 (OR=0.46, p=0.013) and NRAS (OR=0.49, p=0.04) had independent adverse predictive value. In univariate analysis the shorter OS of FLT3-ITD pts was confined to allele ratios≥ 0.5 (FLT3-ITDhigh, p=0.02). In a multivariate analysis accounting for clinical covariates, mutations in NPM1 (Hazard Ratio [HR]=0.45, p<0.0001) and in SRSF2 (HR=0.64, p=0.03) predicted improved outcome, while FLT3-ITDhigh (HR=2.00, p=0.03), mutations in DNMT3A (HR=1.74, p=0.001), ASXL1 (HR=1.84, p=0.002) and NRAS (HR=1.70, p=0.009), but not RUNX1 or TP53, independently predicted worse OS. Significant interactions (eg. NPM1 - SRSF2, p=0.009, NPM1 - DNMT3A, p=0.03) precluded a simple NPM1-based stratification of pts with non-adv cytogenetics. This led to define a new prognostic hierarchy (Figure). The 49 NPM1mut pts with SRSF2 mutation and/or without adverse co-mutations (FLT3-ITDhighDNMT3A, ASXL1 and NRAS) had a median OS of 49.7 months, defining very low risk. NPM1wt pts without adverse co-mutations (n=114) had a median OS of 30.7 months and were considered at low risk. Among pts with ≥1 adverse co-mutation, NPM1 status had no significant prognostic influence (p=0.18). Regardless of NPM1 status, pts with a single (n=187) or ≥2 (n=38) adverse co-mutations (FLT3-ITDhighDNMT3A, ASXL1 or NRAS) had a median OS of 21.0 and 12.0 months, resp, and were considered at intermediate and high risk, resp. In the 83 pts with adv cytogenetics, TP53 mutations predicted shorter OS (p=0.004). Among pts with adv cytogenetics, those without TP53 mutation had a median OS of 12.6 months and were thus classified as high risk while the median OS of the 30 pts with adv cytogenetics and TP53 mutations was only 5.4 months, defining very high risk disease. This stratification resulted in improved OS prediction compared to the full molecular ELN 2017 (C-index 0.63 vs 0.58, resp). This stratification also predicted Relapse-Free Survival (RFS, Figure, p<0.0001). Censoring at SCT did not affect these results. Conclusion. In AML patients older than 60y treated intensively, mutations in 7 genes (NPM1, SRSF2, FLT3, DNMT3A, ASLX1, NRAS and TP53) can refine the prognosis of cytogenetic sub-groups. Figure Figure. Disclosures Cluzeau: MENARINI: Consultancy; CELGENE: Consultancy; JAZZ PHARMA: Consultancy.

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305 Contemporary role of renal mass biopsy: Diagnostic accuracy and outcomes according to biopsy indication

European Urology Supplements ◽

10.1016/s1569-9056(15)60302-5 ◽

2015 ◽

Vol 14 (2) ◽

pp. e305

Author(s):

T. Kwon ◽

C. Lee ◽

M. Sohn ◽

C. Lee ◽

S. Park ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Renal Mass ◽

Renal Mass Biopsy

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Assessment of Oncologic Risk for Clinical Stage T1 Renal Tumors and the Emerging Role of Renal Mass Biopsy

Renal Cell Carcinoma ◽

10.1007/978-1-62703-062-5_6 ◽

2012 ◽

pp. 105-118

Author(s):

Matthew N. Simmons ◽

Steven C. Campbell

Keyword(s):

Renal Mass ◽

Clinical Stage ◽

Renal Tumors ◽

Renal Mass Biopsy ◽

Stage T1

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Primary Therapy with Bortezomib—the Role of Induction, Maintenance, and Re-Induction in Patients with High Risk Myeloma. Update of Results from E2A02.

Blood ◽

10.1182/blood.v112.11.1738.1738 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1738-1738

Author(s):

Angela Dispenzieri ◽

Susanna Jacobus ◽

David H. Vesole ◽

S. Vincent Rajkumar ◽

Philip R. Greipp

Keyword(s):

United States ◽

High Risk ◽

Progressive Disease ◽

Response Rates ◽

Primary Therapy ◽

Newly Diagnosed ◽

High Risk Patients ◽

High Risk Disease ◽

Risk Patients

Abstract Title: Primary Therapy with Bortezomib—The Role of Induction, Maintenance, and Re-Induction in Patients with High Risk Myeloma. Update of Results from E2A02. Angela Dispenzieri, MD1, Susanna Jacobus, PhD2, David Vesole, MD3 and Philip R. Greipp, MD1. 1Hematology, Mayo Clinic, Rochester, MN, United States, 55905 and 2Biostatistics, Eastern Cooperative Oncology Group, Boston, MA, United States, 02115. 3Saint Vincent’s Hospital, New York, NY 10010 Background: Single agent bortezomib as upfront therapy in patients with multiple myeloma (MM) results in response rates of 38% and the drug has been touted to be especially effective in patients with high risk disease. We sought to explore response rate, the role of maintenance and reinduction in a cohort of patients with high-risk MM. Methods: Patients with newly diagnosed high-risk myeloma (beta-2 microglobulin [B2M] >= 5.5., plasma cell labeling index [PCLI] >= 1, or deletion 13q) and adequate organ and functional status were eligible. Patients were treated with bortezomib 1.3 mg/m2 day 1, 4, 8, and 11 every 21 days for 8 cycles as induction. After induction, patients were scheduled to receive bortezomib 1.3 mg/m2 every other week indefinitely. Elective peripheral stem cell mobilization (growth factor alone) was allowed after 4 cycles of bortezomib. Patients relapsing on maintenance schedule had full induction schedule resumed. Responses as defined by the EBMT criteria were determined after each cycle and needed to be confirmed after at least 6 weeks. Results: Between March 15, 2004 and March 10, 2005, 44 patients enrolled on study. Among the 42 eligible treated patients, median age was 63; 51% were male. All patients had high risk disease: deletion 13q (6/41); PCLI >=1% (17/33); t(4:14) (4/27) and B2M >= 5.5 (34/43). Nineteen patients completed induction, i.e. 8 cycles of bortezomib. The most common causes for discontinuing therapy were: progressive disease (n=17), AE (n=7), alternate therapy (n=4), death (n=1), and other (n=11). Forty-eight percent of patients achieved a partial response (PR) or better with induction (0 complete responses, 2 very good PR, 17 PR, 3 minimal responses, 5 no response, 9 progressive disease, and 6 inevaluable or missing). Response rates across risk groups did not differ with a PR or better for patients with deletion 13q (2/6); PCLI >=1% (8/17); t(4:14) (2/4) and B2M >= 5.5 (15/33). One patient’s response was upgraded to CR during maintenance. The rate of painful peripheral neuropathy during all courses of therapy was: grade 1, n=25; grade 2, n=2; and grade 3, n=2. With a median follow-up of 41.6 months (95%CI 36.6–43), 43% of patients have died. Median overall survival (OS) has not been reached (Figure), and the 1- and 2-year OS rates were 88.1% (95%CI 73.7–94.9%) and 76.2% (95%CI 60.3–86.4%) respectively. The median progression free survival (PFS) was 16.3 months (95%CI 6.2–26.6) and the 1- and 2-PFS were 76.7% (95%CI 58.8–87.6%) and 38.3% (95%CI 20.6–55.9%), respectively. Fifteen patients went on to maintenance. The distribution by risk group for patients entering maintenance was not different across groups: deletion 13q, 3/6; high PCLI, 6/17; high B2M, 11/33; t(4;14), 1/4; and p53, 0/2. For those entering maintenance, the median PFS was 19.8 months (Figure), and the 1 year PFS rate was 75% (95%CI 40.8–91.2%). Of the 7 patients progressing on maintenance who received reinduction with bortezomib, no patient responded. Only 2 remain on therapy. Figure Figure Conclusions: In high risk patients, upfront bortezomib results in response rates comparable to those reported for unselected cohorts of newly diagnosed myeloma patients. For patients responding to therapy, maintenance therapy is feasible. Reinduction was unsuccessful in high risk patients failing maintenance.

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