Kidney Cancer: Evaluation and Staging III

Moderated Poster 18

Monday, May 31, 2010 8:00 AM-10:00 AM

617GENOMIC ALTERATIONS ASSOCIATED WITH METASTASISAND POOR PROGNOSIS IN CLEAR CELL RENAL CELLCARCINOMA

Jimsgene Sanjmyatav*, Jena, Germany; Carsten Schwaenen, SvenWessendorf, Ulm, Germany; Markus Kreuz, Leipzig, Germany;Thomas Steiner, Heiko Wunderlich, Kerstin Junker, Jena, Germany

INTRODUCTION AND OBJECTIVES: Clear cell renal cell car-cinoma (ccRCC) is the most frequently encountered renal malignancywith a high metastatic potential and the prognosis of patients in thissubgroup is very poor. Prognostic parameters which can be used for anindividual prognostic evaluation are still not available, So the aim of ourstudy was high resolution screening of genomic imbalances of metas-tasized and non-metastasized primary ccRCC by array CGH in order toidentify regions of DNA copy number changes significantly associatedwith metastasis and clinical outcome of patients.

METHODS: We conducted genome-wide copy number profilesin 56 primary ccRCC including 32 metastasized and 24 non-metasta-sized tumours by array CGH with a median resolution of 2Mbp. Themedian follow up of the patients was 47 months.

RESULTS: Array CGH identified 6 recurrent chromosomal ab-errations: gains of 1q21.3, 12q13.11, 12q13.2 and 20q11.21q13.2 andlosses of 8p11.23p12 and 9p21.3p24.1, which were significantly asso-ciated with metastasis occurrence. In multivariate analysis includingthese aberrations gains of 1q21.3 and of 20q11.21q13.2 and loss of9p21.3p24.1 attained as independent predictors for metastasis withsensitivity and specificity of 81.5% and 95.8%, respectively. Kaplan–Meier survival analysis showed that gains on chromosomes 7, 12, 16and 20q and losses on chromosome 9 have a significant correlationwith disease specific survival. Multivariate Cox-regression analysisrevealed gains of 7q36.3 and of 20q11.21q13.2 and a loss of9p21.3p24.1 as independent prognostic factors for patients‘ outcome.

CONCLUSIONS: Our data suggest that specific common copynumber alterations could serve as independent predictors for metasta-sis occurrence and cancer specific survival in patients with ccRCC. Thepredictive value of these genetic markers is superior to standardparameters like T-category or grading.

Source of Funding: Deutsche Forschungsgemeinschaft

618COMPARISON OF CONTRAST-ENHANCED ULTRASOUND (CE-US) AND COMPUTED TOMOGRAPHY (CT) IN THE EVALUATIONOF COMPLEX CYSTIC RENAL MASSES.

Dario Garcia-Rojo*, Eva Ballesteros, Antoni Malet, Carlos Abad,Angel Prera, Naim Hannaoui, Jesus Munoz, Jose Luis Gonzalez-Sala, Raul Martos, Eduardo Vicente, Julio Martın, Jordi Puig, MiriamBarrio, Anna Darnell, Joan Prats, Sabadell, Spain

INTRODUCTION AND OBJECTIVES: Renal cysts are com-mon incidental findings during the clinical diagnostic workup of patients.In renal cysts, the likelihood of malignancy is assessed using theBosniak classification based on intravenous contrast-enhanced CT. Inthis study, we reported the findings of renal cysts studied with CE-USin comparison with CT.

METHODS: This prospective study included 28 cystic renalmasses. The CT and CE-US images were studied for septa numbers,wall and/or thickness, enhancement degree and for the presence of asolid component by consensus between two radiologists using theBosniak classification. CE-US employed a low-MI technique using 2.4ml SonoVue I.V. Examination of renal cysts was evaluated in renal time

until 2.5 -5 minutes. We offered the practice of surgery for patients withBosniak III and IV cysts detected with CE-US or CT. Those patientswho refused surgery and subjects with Bosniak IIF cysts were fol-lowed periodically by CT and CEUS. We compare the histologicalstudies of surgical specimens with the findings at CE-US and CT. TheCohen statistic was used to analyze agreement between the diagnosticprocedures.

RESULTS: Bosniak Category: Lesions on CE-US were classi-fied as Bosniak category I(n�3),II (n�9),IIf (n�2),III (n�7) or IV (n�7).Lesions on CT were classified as Bosniak category I (n�1),II (n�11),IIf(n�4),III (n�6)or IV (n�6). Concordance between CE-US and con-trast-enhaced CT was high, k�91%, IC (68.3%-98.8%). We observedunderstaging by CT in 2 Bosniak III cysts and in one Bosniak IV cyst.Two of the 3 neoplasms ungraded were surgically removed and histo-logic study showed malignancy. CT has detected calcifications of thecysts in five cases more than the CE-US. But CE-US appreciates betterinternal lesions of the cysts, except for those with a finely calcified wall.Six of the seven patients with Bosniak IV cysts, and only one of the 7patients classified as Bosniak III cysts in any of the radiologic studiesundergone surgery. The histologic findigs of the all 7 resected massesshowed renal cell carcinoma. We did not observed tumor growth in theremaining seven patients who was not operated, with a mean follow-upof 12.3 months (6-24).

CONCLUSIONS: CE-US is a technique equivalent to the CT toassess renal cysts complicated for the Bosniak classification. The jointuse of CT and CE-US provide useful information for deciding themanagement of these lesions. In our experience, CE-Us was found tobe better than TC in the diagnosis of malignancy in Bosniak IIf and IIIrenal cysts. CE-US involves no risks for patients with altered renalfunction.

Source of Funding: None

619SUBTRACTION CT IMPROVES RADIOLOGIST CONFIDENCE INEVALUATION OF ENHANCING RENAL LESIONS

Brian Eisner*, Avinash Kambadakone, Anthony Samir, DushyantSahani, Boston, MA

INTRODUCTION AND OBJECTIVES: Measurement of the de-gree of enhancement of renal lesions is operator dependent. Withsmaller lesions, reliable and reproducible calculation of image en-hancement may be compromised. We undertook this study to deter-mine whether a subtraction image, created with readily available soft-ware, could increase diagnostic confidence.

METHODS: One hundred fifty patients (150 patients, M: F-69:81, Age 22-88) who underwent unenhanced and contrast enhancedMDCT for characterization of a renal mass were included. Imagesubtraction was performed between the unenhanced and the enhancedimages using software on the scanner console. Two experiencedradiologists independently reviewed the images and recorded theirlevel of confidence for detecting presence or absence of enhancementon a 6 point scale (1� definitely absent and 6�definitely present). Thelesions were further by standard criteria, for size, attenuation charac-teristics (Hounsfield values). Final diagnosis was established in allenhancing lesions either by histopathology or follow up imaging withclinical data. The impact of generating and interpreting subtractionimages on the workflow was evaluated.

RESULTS: Out of the 240 lesions (0.6-11.2cm, mean-2.9cm)analyzed, 184 lesions (mean size-2.8cm) showed no enhancement and56 lesions (mean size-3.2 cm) showed enhancement. Combined eval-uation of the routine images with the subtraction images provided thehighest sensitivity (100%) and specificity (99%) in determining en-hancement for both the readers (kappa �0.8). Reader confidence wasalso significantly improved with combined evaluation compared withroutine images and subtraction images alone (p�0.05). The positivepredictive value for determination of enhancement was lower withevaluation of subtraction images alone (71-74%) or hounsfield unitsalone (83-86%) compared with combination subtraction images and

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hounsfield measurements (94-97%). Subtraction images improvedreader confidence in 62-71% of lesions for the determination of en-hancement particularly in hyperdense cysts and in small lesions (�2cm). The average time spent in generating the subtraction images was3 minutes (2-8 minutes).

CONCLUSIONS: With minimal increase in work time, the ad-dition of subtraction CT images to standard evaluation appears toincrease sensitivity, specificity, positive predictive value, and readerconfidence when evaluating renal lesions. At our institution, this hasnow become standard based on its promising results.

Source of Funding: None

620HISTOLOGICAL PREDICTORS OF RENAL FUNCTION DECLINEFOLLOWING LAPAROSCOPIC RADICAL NEPHRECTOMY

Gagan Gautam*, David Lifshitz, Sergey Shikanov, Jocelyn Moore,G. Joel DeCastro, Aria Razmaria, Pablo Marchetti, Arieh Shalhav,Anthony Chang, Chicago, IL

INTRODUCTION AND OBJECTIVES: Renal function decline,although inevitable after radical nephrectomy (RN), occurs to a variableextent in different patients. We assessed histological parameters innon-neoplastic parenchyma of the specimen and their association withsubsequent renal function decline after RN.

METHODS: Forty seven patients (31 male, 16 female) with amean age of 61.4 years undergoing laparoscopic RN in our institutionwere evaluated. Using the Cockcroft-Gault formula corrected for bodysurface area, estimated glomerular filtration rate (eGFR) was calcu-lated at baseline and at last follow up (mean-22.2 months). Theendpoint was defined as eGFR percent change from the baseline (%change eGFR� [Absolute change/baseline] X100%). The specimenswere reviewed by a dedicated renal pathologist and % change eGFRwas correlated with 3 histological features in the non-neoplastic paren-chyma: glomerulosclerosis (GS), arteriosclerosis (AS) and interstitialfibrosis/tubular atrophy (IF/TA). For GS assessment, atleast a 100glomeruli were evaluated and those affected by GS were recorded asa continuous variable (0-25%). AS or the extent of arterial luminalocclusion was semi-quantitatively graded into 4 groups (1� none to5%; 2� 6-25%; 3� 26-50%; 4� �50%). However, due to paucity ofnumbers, groups 1 and 2 and groups 3 and 4 were condensed and ASwas statistically evaluated as either 0 - 25% or �25%. IF/TA, similarly,was observed and evaluated as present or absent.

RESULTS: On average, eGFR declined by 32% from 122 to 83ml/min/1.73m2 after surgery (p � 0.0001). % change eGFR wassignificantly associated with the extent of GS in non-neoplastic paren-chyma (p�0.006), Figure 1. For each 10% increase in GS, eGFRdeclined by 9% from the baseline. Extent of arteriosclerosis and pres-ence IF/TA were not associated with eGFR decline.

CONCLUSIONS: Evaluation of GS in non-neoplastic parenchymacan be used to predict the extent of renal function decline after RN.

Source of Funding: None

621CHARACTERIZING CHANGES IN KIDNEY AND RENAL PELVISCANCER DIAGNOSED FROM 1998 TO 2006 IN THE U.S.

Jan Colli, Sean Clark, Jared Cox*, Birmingham, AL

INTRODUCTION AND OBJECTIVES: Kidney and renal pelviscancer (KCa) rates have increased significantly from 1998 to 2006while mortality rates have declined. Smoking and hypertension whichare risk factor for the disease have declined over the time period. Somestudies suggest that rising KCa incidence rates are a consequence ofhigher detection rates from the increased use of diagnostic imaging. Inthis study, we examine changes in stage and treatment of patientsdiagnosed with KCa from 1998 to 2006. The goal is to characterizechanges in KCa cases that are increasing as a consequence of theupsurge of diagnostic imaging.

METHODS: Data on over 20,000 patients diagnosed with KCadiagnosed from 1998 to 2006 from the National Cancer Data Basewere used to determine changes in stage (I, II, III, IV and unknown) andtreatment (surgery, other and no treatment) rates based on race(Caucasian/African-American), gender and age at diagnoses.

RESULTS: KCa rates have increased by 61% in the U.S.; thelargest increases were in DC and AL (� 87%) while the smallest werein NH and NM (� 3%). The percentages of KCa by stage for 2006 are:stage I (49%); stage II (8%); stage III (12%) stage IV (15%) and stageunknown (16%). The percentages of treatments for 2006 were: surgery(78%), other treatments (11%) and no treatment (11%). Stage I KCarates increased from 33 to 62 cases/100000 for Whites (88%) and from24 to 51 cases/100000 for Blacks (112%) from 1998 to 2006. Stage IIdisease decreased by about 11% for both races. Stage III increased byapproximately 24% for Caucasians and 46% for African-Americans.Stage IV increased by 5% Whites and 16% for Blacks. There weresignificant increases in rates for unknown stage for both races; 7.4 to13.2 cases/100000 for Whites (179%) and 4.6 to 11.4 cases/100000 forBlacks (245%). There were no significant differences in trends in stagebased on gender although rates for males were generally about 65%greater than females. The mean age at diagnoses remain constant forstage I (63 yrs), stage II (63 yrs), stage III (66 yrs) and stage IV (66 yrs)but declined from 69 to 67 yrs for stage unknown. There was asignificant increase in surgery for stage I; from 26 to 54 cases/100000for Whites and from 19 to 46 cases/100000 (136%) for Blacks (136%).There no significant differences in rates for other treatments and notreatment over the period.

CONCLUSIONS: The increase in KCa incidence rates from1998 to 2006 was almost entirely a result of increases in stage I andunknown stage rates. Surgery rates for stage I KCa was the only theonly treatment that increased significantly during the time period.

Source of Funding: None

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