International Journal of Radiation Oncology � Biology � PhysicsS462

reduction in cisplatin dose delivery mainly because of declining renal

function. Acute and late toxicity was similar in the two arms, but che-

moradiation had a greater impact on QOL. Recovery however did follow

and the improved bladder QOL was maintained in surviving patients.

Notwithstanding the small sample size, in terms of local failure rates and

other tumour specific end points interesting trends have emerged in favour

of the chemoradiation therapy.

Conclusions: Whilst weekly cisplatin chemoradiation in this challenging

group of patients has an acceptable acute toxicity profile, it has the po-

tential to impact on Qol .The domains affected do recover with satisfactory

bladder function being sustained. The regimen also holds promise in terms

of potential to improve local control, DFS and OS.

Acknowledgment: This trial was funded by NHMRC Australia;

ClinicalTrials.gov: NCT00330499.

Author Disclosure: N.K. Gogna: K. Advisory Board; Janssen-Cilag

Prostate Cancer Advisory Board.

2634The Role of Postcystectomy Radiation in Treatment of SquamousCell Carcinoma of the Bladder: A SEER AnalysisB. Li, A. Stessin, D. Nori, and C.K. Chao; Weill Cornell Medical College,

New York, NY, NY

Purpose/Objective(s): Squamous cell carcinoma (SCC) is the most

common non-urothelial histology in bladder cancers. Given the high

locoregional recurrence as the primary cause of death, radiation therapy

(RT) is often recommended in the post-operative setting. While large-scale

randomized trials that are dedicated to bladder SCC would be difficult to

accrue to adequate numbers, we utilized the Surveillance, Epidemiology,

and End Results (SEER) database to evaluate the survival benefits.

Materials/Methods: The SEER (1998-2007) was queried for patients with

muscle-invasive (stage II-IV) SCC of the urinary bladder who underwent

complete cystectomy. Information regarding patient demographics, tumor

characteristics, and treatment were obtained. The Kaplan-Meier method

was used to analyze overall survival (OS). Cox proportional hazards

models were used to investigate the association between RT and survival,

with and without adjusting for other factors. Propensity score methods

were used to control for treatment selection bias.

Results: A total of 331 patients from the SEER were included in the

analysis; Majority were received cystectomy alone (n Z 297), while 10%

(n Z 34) received post-operative RT. Factors associated with post-opera-

tive RTwere younger age (pZ 0.03) and more advanced stage at diagnosis

(p<0.001). After adjustment for confounding using propensity scores, the

addition of RT was not associated with an OS benefit (p Z 0.55). Median

survival was 21 months for patients treated with cystectomy alone and 18

months for post-operative RT. Cox regression analysis confirmed the lack

of improvement in OS among patients who received post-operative RT

(HR Z 0.88, 95% CI Z 0.62 - 1.25, p Z 0.47).

Conclusions: In spite of limitations of this population-based study, the lack

of a survival benefit associated with post-operative RT suggests that RT for

muscle-invasive SCC of the urinary bladder might be used with caution.

Further studies are needed to identify any subsets of patients with bladder

SCC who may benefit from post-cystectomy radiation.

Author Disclosure: B. Li: None. A. Stessin: None. D. Nori: None. C.K.

Chao: None.

2635Novel Predictive MicroRNA Signature in the Setting of SelectiveTrimodality Bladder Preservation TherapyT. Lautenschlaeger,1 J.A. Efstathiou,2 W.U. Shipley,2 W. Meng,1

J. McElroy,1 J.J. Paly,3 A. Ibrahim,1 P. Nguyen,4 S. Volinia,1 P. Saylor,2

R.H. Clayman,2 S. Clinton,1 A. Mortazavi,1 C. Wu,5 and A. Chakravarti1;1The Ohio State University, Columbus, OH, 2Massachusetts General

Hospital, Boston, MA, 3Massachusetts General Hospital, Boston, MA,4Ohio State University, Columbus, OH, 5Massachusetts General Hospital,

Boston, MA

Purpose/Objective(s): Trimodality therapy with maximal transurethral

resection of bladder tumor (TURBT) and definitive chemoradiation

reserving cystectomy for salvage of local recurrence is an accepted treat-

ment alternative to upfront cystectomy for selected patients with muscle

invasive bladder cancer (MIBC). We sought to identify novel biomarkers

predicting outcome after such selective bladder preservation therapy.

Materials/Methods: We used publically available miR-seq data from

cystectomy patients (TCGA) and Cox proportional hazards (CPH) models

were used to identify miRs individually associated (p<0.05) with overall

survival (OS) in the cystectomy cohort (n Z 144, 30% pT2, 54% pT3,

15% pT4, 61% pN0, 39% pN1/2/3). These genes were then fit into a

multivariate CPH model. The sum of the products of the coefficients and

standardized miR expression was computed to generate a score for each

patient. We performed microRNA (miR) deep sequencing on 40 TURBT

specimens from patients who underwent selective bladder preservation

therapy (48% cT2, 50% cT3, 2% cT4). Small RNAs were sequenced on a

Applied Biosystems SOLiD 4, and analyzed using small RNA Analysis

Pipeline Tool and stringent parameters. Data was transformed to z scores

(within data set) to allow across data set comparisons. The same score

function developed in the cystectomy cohort (with the same coefficients)

was then used to classify patients in the bladder preservation cohort.

Scores were dichotomized (median-split) and log rank test performed.

Results: A 7-microRNA signature score including miR-152, miR-423, miR-

10b, miR-181a2, miR-361, miR-221, and miR-15b was developed in the

cystectomy cohort. In the bladder preservation cohort a high 7-microRNA

signature score was associated with improved distant metastasis free survival

(HR Z 0.21, 95% CI: 0.06-0.63, log-rank p Z 0.005), disease specific

survival (HR Z 0.25, 95% CI: 0.07-0.75, log-rank p Z 0.012), and OS (HR

Z 0.33, 95% CI: 0.15-0.71, log-rank p Z 0.004). The score remained

significant on multivariate analysis when including clinical T-stage. In the

cystectomy cohort a higher 7-microRNA signature score was associated

with worse OS (HR Z 4.9, 95% CI: 2.3-10.8, log-rank p Z 0.00001),

suggesting that this marker may be predictive for therapy-specific OS out-

comes. The score remained significant in the cystectomy cohort on multi-

variate analysis when including pathological T-stage and N-stage.

Conclusions: A novel 7-micro RNA signature may help identify patients

with improved survival outcomes following initial trimodality bladder

preservation therapy for MIBC. This preliminary data must be further

validated in both chemoradiation and cystectomy cohorts. If validated,

such a signature may help with initial treatment selection including those

patients who may benefit from neoadjuvant or further adjuvant therapy.

Author Disclosure: T. Lautenschlaeger: None. J.A. Efstathiou: A.

Employee;Massachusetts General Hospital. G. Consultant; Advisory Board

for Medivation/Astellas and Bayer. S. Leadership; Co-chair NCI Bladder

Task Force, Co-chair NRG Comparative Effectiveness Subcomittee. W.U.

Shipley: S. Leadership; Board member of the Bladder Cancer Advocacy

Network, the Woods Hole Oceanographic Institute and the NCI Bladder

Cancer Task Force.W.Meng:None. J.McElroy:None. J.J. Paly:None.A.

Ibrahim:None. P. Nguyen:None. S. Volinia:None. P. Saylor:None.R.H.

Clayman:None. S. Clinton:None.A.Mortazavi:None.C.Wu:None.A.

Chakravarti: E. Research Grant; Brain Tumor Funders Group Grant;

Goldhirsh Brain Tumor Research Award; NIH/NCI 1R01CA11522358;

NIH/NCI 1R01CA1145128;NIH/NCI/CTEP 1R01CA169368; NIH/NCI

2K12CA133250-06; NIH/NCI 1U10CA180850-01. S. Leadership; ASCO;

AACR; ACRO; EORTC; RTOG; ONO-C; NIH/NCI CBSS; OSU; American

Board of Radiology; International Society for Radiation Neuro-Biology;

BIT Life Sciences.

2636Patterns of Referral to Radiation Oncology Among Patients WhoUndergo Cystectomy for Invasive Bladder Cancer in Ontario: APopulation-Based StudyK. Zaza, C. Booth, R. Siemens, P. Peng, D. Berman, X. Wei, W. Kong,

and W.J. Mackillop; Queen’s University, Kingston, ON, Canada

Purpose/Objective(s): Radical radiation therapy (RT) is a reasonable

alternative to cystectomy for some patients with invasive bladder cancer,