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168 Abstracts

  • Introduction & Objectives

    Dose to the bladder trigone is associated with increased Genito-Urinary (GU) toxicity in prostate radiotherapy studies. Its role in Muscle Invasive Bladder Cancer (MIBC) is unknown. The relationship between GU toxicity grade (G) and dose to trigone was determined in patients who received high-dose focal tumour boost (≤70Gy) within a prospective phase 1 image-guided adaptive radiotherapy dose escalation study (NCT01124682).

    Material & Methods

    Patients with localised MIBC were treated with a plan of day approach, treating whole bladder to 52Gy and tumour to 70Gy in 32 fractions. Following completion of treatment, bladder trigone surrogate structure was retrospectively contoured on the planning CT as a triangle-shaped region at the posterior wall that encompassed the transition of the urethra into the bladder caudally and the ureteric orifices cranially. Cumulative dose to trigone was determined by summation of selected plans used for treatment delivery. ROC analysis was used to identify significant dose constraints (AUC > 0.6 and p < 0.05) predictive of acute peak and emergent peak ≥G2 toxicity as measured using CTCAE v3.0. AUC cut point values were determined by Younden index. Peak toxicity was the highest score occurring either at baseline, weekly during radiotherapy or at 4, 8 and 12 weeks following radiotherapy. Emergent peak score was the difference between peak score (up to 12 weeks) during follow-up and baseline. The probability of peak and emergent ≥G2 acute events was calculated using logistic regression. Constraints predicting 20%, 30%, 40% and 50% probability of acute GU toxicity was determined.

    Results

    20 patients (14 males; 6 females) recruited to the study protocol between June 2012 and May 2014 were evaluated. All patients had stage T2-T3N0M0 transitional cell carcinoma of the bladder. Median age was 73 years (range 50-90). Baseline G0, G1 and ≥G2 toxicity was 45%, 45%, and 10%; peak G0, G1 and ≥G2 toxicity was 0%, 30% and 70%; emergent G0, G1 and ≥G2 toxicity was 20%, 55% and 25%. No G4 toxicity was seen at any time point. Significant association of emergent ≥G2 toxicity was identified at trigone V60 >5.6cm3 (AUC 0.81, 95% CI 0.60-1.0; p=0.040), V65>5.6cm3 (AUC 0.89, 95% CI 0.69-1.0; p=0.010), V70>3.6cm3  (AUC 0.87, 95% CI 0.65-1.0; p=0.016) and V70>61.0%.  (AUC 0.81, 95% CI 0.57-1.0; p=0.040). No significant AUC was associated with peak ≥G2 toxicity. Table 1. Predicted probability of emergent ≥G2 acute GU toxicity.

    Trigone Threshold constraint for % predicted probability
    Relative volume (%) Absolute volume (cm3)
     20% 30% 40% 50% 20% 30% 40% 50%
    V50 99.3 99.4 99.5 99.5 7.9 7.9 7.9 7.9
    V55 79.5 80.5 81.0 85.0 6.0 6.1 6.3 6.4
    V60 60.0 62.0 65.0 68.5 4.5 4.7 4.9 5.2
    V65 50.0 54.5 58.0 61.5 3.7 4.0 4.3 4.5
    V70 28.5 32.0 36.0 40.0 2.1 2.3 2.6 2.9

    Conclusions

    Bladder trigone dosimetric predictors of acute GU toxicity have been characterised and novel constraints are proposed to reduce GU events in future bladder radiotherapy dose escalation protocols following validation. Further work is also neeeded to determine impact of trigone dose on long-term GU toxcity in bladder radiotherapy.

  • Introduction & Objectives

    Upper urinary tract urothelial carcinoma (UUT-UC) is relatively rare, account for 5 to 10% of all urothelial carcinomas. The biologic behavior and clinical outcomes of patients with UUT-UC are dependent on the pathological (pT) stage, grade and lymphovascular invasion (LVI) in some studies. However, urothelial carcinomas in the upper urinary tract as well as bladder can exhibit a wide variation in biological behaviours and clinical outcomes. Surviving is a member of the inhibitor of apoptosis protein family that is over-expressed in many malignancies including urothelial carcinomas but rarely detected in normal differentiated adult tissues. To our knowledge, only several studies have dealt with surviving expression in UUT-UC. We retrospectively studied the expression of surviving in UUT-UC using immunohistochemical methods and determined whether its expression is associated with prognosis.

    Material & Methods

    Forty-six UUT-UC specimens obtained at nephroureterectomy were examined for expression of surviving with a mouse monoclonal antibody (Clone 12C4, Dako, Glostrup, Denmark) against surviving protein. The immunohistochemical results were analyzed by evaluating the percentage of tumour cells with positive staining on the total neoplastic cell count from 10 representative fields at 400-magnification. The cutoff was estimated as 20% of antibody-stained cells, at which point the sample was considered immune-positive. Cancer-specific survival (CSS) was performed according to the Kaplan-Meier method, and the Cox proportional hazard model was used to compare the relative influence of different prognostic factors. The median-flow-up was 41 months (range: 3-157 months).

    Results

    Of 46 patients 21 (46%) had surviving positive urothelial carcinomas. The survivingimmunoreactivity was significantly related to high pT stage (p=0.0454) and high grade (p=0.0085). The 10-year CSS outcomes for the surviving immune-positive group and negative group were 28% and 78%, respectively (p=0.0131). In a univariate analysis, high pT stage (p=0.0071, pT3 or more n=24 vs pT2 or less n=22), high grade (p=0.0109, high n=25 vs low n=21), positive LVI (p=0.0118, positive n=22 vs negative n=24) and surviving expression (p=0.0210, positive n=21 vs negative n=25) were associated with unfavourable CSS. However, multivariate analysis including these significant variables by univariate analysis showed that the parameters were not significantly related to the CSS.

    Conclusions

    Although in multivariate analysis no independent influence of survivin on patient prognosis was found, surviving expression may be a potential predictive marker of prognosis in UUT-UC. However, prospective study including a large number of cases is needed to confirm the prognostic utility of surviving.

  • Introduction & Objectives

    One of the surgical techniques utilized to treat prostate cancer is Radical Perineal Prostatectomy (RPP). This technique offers good anatomic visualization and allows for precise dissection of the prostate away from the Neurovascular Bundles (NVBs). Our objective was to evaluate urinary continence following RPP.

    Material & Methods

    66 RPPs were conducted between 2013 and 2015. The mean age of the patients was 62 (53-71) years. The mean preoperative PSA level was 6.9 (4.2-9.8) ng/ml. The mean prostate volume was 42 (21-72) cm3. All patients had the Gleason score of ≤ 7. 47 patients (71%) had clinical stage T1, and 19 patients (29%) had T2. The surgeries were performed using Young’s suprasphincteric approach modified by Belt. All patients were divided into 2 groups. In group 1, the patients (n=45, 68%) underwent nerve-sparing RPP. In group 2, the patients (n=21, 32%) underwent non-nerve-sparing RPP. This study evaluated urinary continence in patients with and without the preservation of the NVBs.

    Results

    In group 1, catheters were removed on postoperative day 6 or 7. In group 2, they were removed on postoperative day 6, 7, or 8. Following catheter removal, 33 patients in group 1 (73%) regained full urinary continence, and 12 patients (27%) had Grade 1 incontinence, while in group 2, full urinary continence was observed in 10 patients (48%), and Grade 1 incontinence in 11 patients (52%). No cases of Grade 2 incontinence or total urinary retention were noted. At 6 months of follow-up, in groups 1 and 2 full urinary continence was observed in 39 patients (87%) and 15 patients (72%), respectively. At 12 months of follow-up, in groups 1 and 2 full urinary continence was observed in 44 patients (98%) and 18 patients (86%), respectively.

    Conclusions

    Perineal access provides better visualization of the operative field, which allows for precise separation of the NVB and precise vesicourethral anastomosis. The advantages of nerve-sparing RPP are shorter catheterization time and faster return of full urinary continence. However, at 1 year of follow-up, no significant differences in urinary continence between the two groups were observed.

  • Introduction & Objectives

    With its excellent resolution of adipose tissue, CT presents precise quantitative assessment of visceral fat accumulation. We assessed the impact of visceral fat accumulation on progression free and overall survival in patients treated with 
    systemic therapy for metastatic renal cell carcinoma.

    Material & Methods

    This retrospective cohort study included 114 patients treated with systemic therapy for metastatic renal cell 
    carcinoma between 2007 and 2015 at Keio university hospital in Japan. The visceral fat area was measured at 
    the level of umbilicus using CT. The tomographic attenuation of the adipose tissue was defined to be between 
    −50 and −150 HU. A visceral fat area ≥100cm2 was used as the definition of visceral fat accumulation. 
    Progression free and overall survival was compared according to visceral fat accumulation.

    Results

    The mean visceral fat area was 107.4 ± 62.8 cm2. In the whole cohort, the median progression free survival in first 
    line treatment was 12.0 month. The median overall survival was 42.5 month. According to Memorial Sloan-Kettering Cancer Center classification, 31 patients were favorable risk, 61 were intermediate risk, and 22 were 
    poor risk; median overall survival for these groups were 76.9, 40.8, and 23.7 months, respectively (P<0.0001). 
    Visceral fat accumulation correlated with improved progression free (P=0.0070) and overall survival (P=0.0001). 
    On multivariate analysis, visceral fat accumulation (P=0.0290) and Memorial Sloan-Kettering Cancer Center classification (P=0.0085) were independent indices to predict progression free survival 
    in first line treatment. In addition, visceral fat accumulation (P=0.0153) and Memorial Sloan-Kettering Cancer Center classification (P=0.0004) independently predicted overall survival.

    Conclusions

    The precision of CT imaging for measuring visceral fat area provides useful clinical venue to predict prognosis 
    for metastatic renal cell carcinoma. Visceral fat accumulation may be a useful and independent indicator for a 
    better prognosis in patients treated with systemic therapy for metastatic renal cell carcinoma.

  • Introduction & Objectives

    Amyloidosis is a rare disorder that results from the extracellular deposition of misfolded proteins in fibrils responsible for tissue compression, damage and functional impair. There are 4 main types of amyloid proteins: AL – light chain - plasma cell proliferation and the systemic amyloid, AA type – increased in chronic inflammatory states, Aß amyloid- brain lesions of Alzheimer patients, ATTR - familial amyloid polyneuropathies. Amyloidosis may be localized or systemic. Localized amyloid of the lower urinary tract is uncommon and amyloid of urethra is exceedingly rare. Since 1909 50 cases of urethral amyloid were reported.

    Material & Methods

    A clinical case report.

    Results

    We present the case of a 29 year old male with 3-4 months duration of lower urinary tract symptoms including dysuria, macroscopic hematuria, hematospermia and urethral discharge. He presented with repeatedly negative urine cultures, urine cytology PAPI, and a complete STD screen negative. On clinical examination an endured elastic mass with approximately 4cm was palpable at the bulbar urethra. Physical examination was otherwise unremarkable. No post-micturition residual urine was detected on ultrasound. MRI showed hypertrophy of bulbar urethral wall with low signal intensity on T1-weighted, T2-weighted and an enhancement after application of Gadolinium contrast. A transurethral biopsy was obtained from a group of white solid with superficial papillary character masses 8cm proximal to the external urethral orifice and sent to pathological examination and an optical urethrotomy performed. The examined tissue stained positive with Congo red and birefringence detected under polarized light – amyloid. Immunohistochemistry excluded the presence of kappa and lambda chains, excluding AL type. The patient was seen 1 month after the surgery, there was a regression of the LUT symptoms by 40% and the patient referred to Internal Medicine for further investigations.

    Conclusions

    Amyloid in the urethra is a rare diagnosis, it mimics primary urethral tumor, non-specific urethritis or stricture and its management is mostly conservative. A multidisciplinary approach is recommended.

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