bluuebunny/crossref_metadata_2025 huggingface dataset:
An age-corrected matched-pair study of erectile function in patients treated with adaptive intensity modulated radiation therapy (IMRT) versus high-dose-rate brachytherapy (HDR) in prostate cancer.
Authors: Warner Jillian Nicole , Marina Ovidiu , Grills Inga S. , Shah Chirag , Wallace Michelle , Marvin Kimberly , Ye Hong , Gustafson Gary S. , Brabbins Donald , Kestin Larry Llyn , Ghilezan Michel , Martinez Alvaro
Published: February 2017

225

Background: Increasing age is a likely contributor to erectile dysfunction (ED) after radiotherapy for prostate cancer. A matched-pair (MP) analysis, with age as a criterion, was used to investigate ED after IMRT and HDR monotherapy for prostate cancer.

Methods: 430 patients with low (63%) or intermediate risk (37%) prostate cancer with full or partial erectile function were treated between 4/00 and 9/10 with IMRT (n=215) or brachytherapy (n=215). Patients with follow up (FU) <1y were excluded. IMRT dose was 70.2–82.8 Gy (median 75.6) in 1.8 Gy/fx. HDR was given as 9.5 Gy x 4 (median), 13.5 Gy x 2 or 12 Gy x 2. MP, univariate, and multivariate analyses examined ED using CTCAEv4. Match criteria were age (±5y), Gleason (6,7), T stage (T1, T2), and PSA (<4, 4–10, >10). BF was by modified Phoenix criteria (nadir+5 for 2y, nadir+2 after).

Results: Median FU was 3.4y (range 1–7.1) for IMRT and 3.1y (range 1–10.9) for HDR. There was no difference in PSA (4.8 vs. 4.6, p=0.4), T stage (88% vs. 88% T1, p=1.0) and Gleason score (63% vs. 63% 6, p=1.0) between IMRT and HDR. Despite age matching, IMRT patients were older (median 65 vs. 62 y, p=0.05). Pre-treatment potency grade 0, 1, and 2 were found in 70%, 14% and 15% of IMRT and 69%, 20% and 11% of HDR patients. 5y OS, CSS, and BF were 100%, 100% and 2.4% for IMRT, and 99% (p=0.35), 100% (p=1.0), and 10.6% (p=0.001) for HDR. On subset analysis of pre-treatment grade 0 patients, univariate analysis showed HDR (p<0.001), increasing Gleason (p=0.05) and increasing FU time (p<0.001) correlated with post-treatment ED, while age (p=0.32), PSA (p=0.46) and T stage (p=0.76) did not. On multivariate analysis, increasing FU time correlated with ED (p<0.001), while treatment type (p=0.10) and Gleason (p=0.49) did not.

Conclusions: Both IMRT and HDR yield comparable low (25%) rates of 1+ ED for patients with no ED at baseline. Increasing age does not appear to significantly impact ED for both IMRT and HDR.

[Table: see text]
Palliative transurethral resection in men with castration-resistant prostate cancer (CRPC): Minimally invasive procedure with minimal morbidity?
Authors: Piper Charlotte , Epplen Robin , van Erps Thomas , Pfister David J. K. P. , Porres Daniel , Heidenreich Axel
Published: February 2017

233

Background: About 20 to 30% of men with CRPC with a prostate in situ will develop subvesical obstruction due to locally progressing prostate cancer with time. Treatment options include palliative TURP, urinary diversion by transurethral or suprapubic catheters. There are only few reports critically evaluating the outcome of palliative TURP and the development of associated symptoms of locally progressing CRPC.

Methods: We retrospectively reviewed all patients who underwent palliative TURP for locally advanced CRPC with regard to the functional and oncological outcome. In addition, we analysed the frequency of complications associated with locally advanced (LA) CRPC. Patient with incidental prostate cancer were excluded from the analysis.

Results: Between 2004–2010 a total of 83 patients were identified. The mean age of the patients was 76 (60–91) years. Mean PSA at time of TURP was 78 (1–253) ng/ml. Initial therapy included androgen deprivation monotherapy in 67.8%, radiation therapy in 28.6% and active surveillance in 3.4%.The mean size of the prostate was 40 (15–130) ml, the mean resected prostate weight was 18.6 (2–56) g. The mean Gleason score was 8.3 (6–10). The indication for palliative TURP was subvesical obstruction with a postvoid residual urine > 100ml in 68.8 %, recurrent gross hematuria in 13.2% and acute urinary retention in 18.1%. 19 (2.9%) pts demonstrated uni- or bilateral upper urinary tract obstruction necessitating drainage by endoluminal stenting or percutaneous nephrostomy. The mean catheterization time was 3.4 (2–6) days; postoperative complications developed in 15 (18.1%) pts and included: urinary retention in 2 pts, intravesical blood clots in 3 pts, permanent suprapubic catheter in 3 pts, stress urinary incontinence in 2 pts and re-do TURP in 3 pts. Perioperative mortality was 0% and after a mean follow-up of 3.6 years, 27 (32.5%) pts had died due to prostate cancer.

Conclusions: Palliative TURP in men with LA-CRPC is fairly safe, but side effects are higher compared to conventional TURP. Due to a high frequency of involvement, the upper urinary tract has to be screened prior to palliative TURP.
Multi-institutional outcomes following LDR brachytherapy in patients with higher-risk prostate cancer.
Authors: Conroy Ruth , Hoskin Peter , Bottomley David , Mandall Paula , Swindell Ric , Wylie James
Published: February 2017

238

Background: We report the outcomes for a cohort of men with higher risk prostate adenocarcinoma treated with LDR brachytherapy in a multi-institutional UK practice.

Methods: 217 men treated between 2003-2007 with Iodine-125 brachytherapy at Christie, Leeds and Mount Vernon were identified from a multi-institutional database. Higher risk was defined as patients with ≥ 2 D’Amico intermediate risk factors (PSA 10-20, GS 7 or clinical T2c) or ≥1 high risk factor (PSA > 20, GS ≥ 8). Kaplan-Meier methods were used to estimate biochemical relapse free survival (BRFS) defined using both Phoenix and ASTRO definitions. A univariate analysis was performed to assess the significance of Gleason score, PSA, T-stage, pre- or post-implant dosimetry, and additional hormones on BRFS.

Results: The median age was 65yrs (43–79yrs) with a median PSA follow up of 62months (14–102months). Median pre-implant doses (ranges) were: V150 59.6(43.7–89.8), V200 20.1(11.6–36). 75 patients had post-implant dosimetry, median dose (range) was: D90 132.8Gy (75-192Gy). No patients had external beam radiotherapy. 67 patients had additional hormone treatment, median duration 7 months (3 – 22 months). The 3 and 5 year BRFS as defined by Phoenix were 85.4% and 74.4% and as defined by ASTRO were 76.6% and 69.8%. On univariate analysis there were no statistically significant predictors of inferior outcome.

Conclusions: Single modality LDR brachytherapy is a well established treatment for low risk prostate adenocarcinoma reporting excellent long term BRFS. Some authors have advocated the addition of external beam radiotherapy when treating higher risk disease. These results show that good BRFS can be obtained with LDR brachytherapy alone and no additional benefit has been shown by the addition of adjuvant hormone therapy. These results appear comparable with other treatment modalities available to these patients.
Primary androgen deprivation (PAD) followed by active surveillance for newly diagnosed prostate cancer (PC).
Authors: Scholz Mark Creamer , Groom Meg , Kaddis Andrew , Lam Richard Y. , Jennrich Robert
Published: February 2017

244

Background: Men undergoing local therapy (LT) with radiation or surgery incur substantial risk of permanent sexual, urinary and rectal toxicity. Active surveillance is only recommended for men with Low-Risk PC who have < 34% biopsy cores positive. Studies of PAD as an alternative to LT are sparse.

Methods: Retrospective analysis of 102 men with localized PC administered 12 months of an LHRH agonist and antiandrogen (PAD) followed by immediate biopsy (BX1). Outcome assessed: The incidence of implementing further treatment with either LT or androgen deprivation (AD) if there was subsequent progression on active surveillance (PAS) or if BX1 was positive. Post PAD monitoring included quarterly PSA testing, follow-up biopsy and imaging with color doppler ultrasound and endorectal MRI. Participants were screened for heart disease and osteoporosis and monitored for changes in body weight, BP, liver enzymes, anemia, blood sugar and cholesterol. All received empiric bisphosphonates and 5-alpha reductase inhibitors and were instructed to eat a low fat diet and perform resistance exercise.

Results: Patient characteristics: D’Amico risk category (DRC) Low: n=22; Intermediate: n=30; High: n= 50. Baseline factors assessed as potential predictors of PAS: Age, PSA, PSA velocity, PSA nadir, Gleason, % core biopsies, stage, prostate volume, DRC. Baseline medians for the 102 men: Age 67.3, PSA 7.8, Gleason 3+4, Cores > 50%, stage T1c, prostate volume 45cc. 55 men had PAS and required LT and/or AD over a median of 7.3 years follow up. Type of treatment administered after PAS by DRC: Low: AD 1, LT 3. Intermediate: AD 5, LT 10. High: AD 15, LT 21. Two men developed clinical progression. There were no PC deaths. Four men died of other causes: lung CA, melanoma, emphysema and MI. Only DRC (p<0.01) and PSA nadir (p<0.04) predicted PAS (3 men had PSA nadir > 0.1 and all were positive at BX1).

Conclusions: PAD frequently induces durable remissions in men with Low and Intermediate risk PC despite a high prevalence of > 50% core biopsies positive at baseline in this population. 38% of the 55 men with PAD elected additional AD rather than undergoing LT suggesting that for some men enduring the toxicity profile of AD was preferable to the perceived risks of LT.
Tolerability of and biochemical control of permanent Pd-103 brachytherapy followed by external beam radiotherapy for localized prostate adenocarcinoma.
Authors: Richter Samuel M. , Aridgides Paul D. , Shapiro Oleg , Aronowitz Jesse N. , Bogart Jeffrey
Published: February 2017

245

Background: The optimal sequencing of brachytherapy and external radiotherapy (EBRT) for patients receiving combined therapy for localized prostate cancer has not been established, and in this series we report our experience of patients treated with brachytherapy followed by EBRT.

Methods: Retrospective review of patients treated with combined Pd-103 brachytherapy and EBRT with minimum of 2 years of follow-up. Variables assessed included T stage, Gleason score, pre-treatment PSA, use of androgen suppression (ADT), EBRT dose and brachytherapy dose. Biochemical failure was defined as a PSA rise of ≥ 2 ng/mL above nadir.

Results: 87 patients received Pd-103 brachytherapy (median 80 Gy) followed by EBRT (median 45 Gy). Median age was 65 years (49–80). By risk groupings (Zelefsky) 26.4% of patients were low risk, 47.1% were intermediate risk, and 26.4% were high risk. Most low risk patients had either perineural invasion or ≥ 50% involved biopsy cores. Neoadjuvant and concurrent ADT was given in 21% of patients. With a median follow-up of 56 months (range 24 to 113), there were 4 failures (all in the intermediate or high risk group), with an overall 5-year biochemical failure free survival (BFFS) of 91.8%. 2 patients had documented distant failures, while none of the presumed local failures had a positive biopsy. There was no statistical difference in BFFS based on risk group, T stage, Gleason score, initial PSA, or ADT use. The median PSA nadir was 0.1 and occurred at a median of 30 months from brachytherapy. A nadir of ≤ 0.5 was seen in 87% of patients and was associated with improved 5-year BFFS (100% vs 22%, p<.0001). The median time to PSA nadir for patients < 60 years was 34.5 months compared to 26.5 months in patients ≥ 60 (p=.036). Overall, treatment was well-tolerated with no cases of late Grade ≥ 2 rectal or urinary toxicity reported.

Conclusions: Excellent long-term disease control and low morbidity was observed for patients with localized prostate adenocarcinoma treated with interstitial brachytherapy followed by EBRT. Future prospective research assessing the relative therapeutic ratio of alternate sequencing approaches would appear warranted.
Awareness, concern, and communication between physicians and patients on bone health in nonmetastatic prostate cancer.
Authors: Moul Judd W. , Ferenz Krag S , Mautner Beatrice Delhey
Published: February 2017

246

Background: Little is known about physicians’ (MDs) and prostate cancer (PC) patients’ (pts) levels of awareness or concern about bone health or how/when MDs discuss bone health with at-risk pts. An online survey was conducted to explore these issues and evaluate knowledge levels and attitudes about cancer treatment-induced bone loss (CTIBL).

Methods: A total of 4,403 oncologists and 4,961 urologists randomly selected from the American Medical Association master physician list, 533 oncologists from the Harris Physician Panel, and 3,400 pts from Harris’ Chronic Illness Panel were invited to participate in the survey. Surveys lasted on average 10 minutes; MD and pt surveys were weighted to be representative of the populations of interest. Descriptive statistical analyses were used.

Results: Of those invited, 113 urologists and 63 oncologists completed the survey. The 186 PC pts who answered the survey (median age, 74 yrs; median time since PC diagnosis, 88 mos.) included 96 pts with nonmetastatic disease. Current or prior ADT was reported by 96% of pts. Of these pts, 48% were aware of CTIBL, 23% of whom were concerned about it and 55% of whom had discussed it with their MD. As many as 46% of pts obtained information on bone health exclusively from their healthcare team, rather than seeking information from other sources. Both oncologists and urologists (98% and 90%) considered CTIBL to be a serious issue for their patients, however, more oncologists than urologists perceived that their pts were concerned about CTIBL (71% vs 36%). More oncologists than urologists expressed concern about fractures due to CTIBL (58% vs 46%), and indicated that treatment-induced fractures would require additional intervention (91% vs 76%), treatment interruption (61% vs 43%), or change in treatment (55% vs 42%).

Conclusions: Bone health is considered a serious issue for patients with nonmetastatic PC treated with ADT by both oncologists and urologists. However, there remains a gap in physician-patient communication regarding CTIBL and its clinical consequences. As primary sources of information for pts, MDs should proactively educate pts on CTIBL, its consequences, appropriate monitoring, and treatment options.
Overcoming docetaxel resistance in advanced castration-resistant prostate cancer (CRPC): A phase I/II trial of the combination of temsirolimus and docetaxel.
Authors: Duran Ignacio , Montagut Clara , Calvo Emiliano , Galtes Susana , Navarrete Alicia , Rodriguez-Pascual Jesus , Hidalgo Manuel , Rodriguez-Moreno Juan Francisco , Cubillo Antonio , Garcia Antonia , Sanchez Lorena , Barbas Coral , Viqueira Andrea , Bellmunt Joaquim
Published: February 2017

250

Background: Mechanisms of resistance to docetaxel (D) are not fully understood. Preclinical work showed that administration of temsirolimus (T) between courses of D delays the growth of PTEN deficient tumors in xenografts. (Wu et al. Cancer Res 2005) The current study aims to determine the recommended phase II dose (RPTD), toxicity, pharmacokinetics (PK) and preliminary activity of D in combination with T in CRPC patients (pts).

Methods: Pts aged ≥ 18 with advanced solid tumors refractory to standard therapy, ECOG ≤2, adequate bone marrow and renal function were eligible. D was given once q. 3 weeks along with T on days 2, 9 &16. The protocol was later amended and day 9 of T omitted due to excessive myelotoxicity. A 3+3 rule dose escalation was used with the next dose levels (DL) planned: DL1: D 50mg/m2, T 15 mg; DL2: D 65mg/m2, T 15 mg; DL3: D 75mg/m2, T 15 mg; DL4: D 75mg/m2, T 25 mg. An expanded cohort for pts with CRPC who have progressed to D will enroll pts once the RPTD has been defined.

Results: To date 13 pts have been enrolled, median age = 65 (range 35–76), 9 male and 8 ECOG 0, Forty-seven cycles (median: 2; range: 1–9) were administered. The most frequent related adverse events (AEs) of all grades expressed as % of cycles were: leucopenia (80.8%), hyperglycemia (70.2%), anemia (68.1%) and hypercholesterolemia (65.9%). The most common Grade 3–4 AEs as % of cycles were: leucopenia (27.6%), neutropenia (29.7%), and hypophosphatemia (23%). Two pts in DL2 experienced dose limiting toxicities (DLT) consisting of intolerable grade 2 mucositis and febrile neutropenia respectively. DL1 was expanded and 3 additional pts treated with no DLTs. No drug-drug PK interactions were observed. Among 13 pts evaluable for response, 6 (2 pancreas, 2 CRPC, 1 rectal and 1 sarcoma) achieved stable disease. One pt with CRPC who had previously progressed on docetaxel received 9 cycles of treatment with sustained clinical benefit. The expanded cohort for CRPC patients is opened and recruiting.

Conclusions: T and D can be safely combined at reduced doses of both agents with no PK interaction. Preliminary antitumor activity has been observed in CRPC patients. Data on the expanded cohort will be presented.
A novel risk stratification to predict local-regional failures in urothelial carcinoma of the bladder after radical cystectomy.
Authors: Baumann Brian Christopher , Guzzo Thomas J. , He Jiwei , Keefe Stephen Michael , Tucker Kai , Bekelman Justin E. , Hwang Wei-Ting , Vaughn David J. , Malkowicz S. Bruce , Christodouleas John Paul
Published: February 2017

262

Background: Invasive urothelial bladder carcinoma is typically treated with radical cystectomy (RC) plus pelvic lymph node dissection (PLND) +/− chemotherapy. Local-regional failures (LF) following cystectomy are a significant problem. Adjuvant radiation therapy (RT) could potentially reduce LF but currently has no defined role because of previously reported morbidity. Modern RT techniques with improved normal tissue sparing have rekindled interest in adjuvant RT. Stratifying patients by differing LF risk could facilitate selection for adjuvant RT.

Methods: From 1990–2008, 442 patients with urothelial bladder carcinoma were prospectively followed at the University of Pennsylvania after RC+PLND +/− chemotherapy with routine pelvic CT or MRI. Univariate and multivariate competing risk analyses identified subgroups with differing LF risk.

Results: On univariate analysis, stage pT3-4, total nodes removed (<10 vs. ≥10), positive margins, positive nodes, hydronephrosis, lymphovascular invasion, and mixed histology were significant predictors of LF, while use of chemotherapy, number of positive nodes, surgical diversion type, age, gender, race, smoking history and BMI were not. Node density was a marginal predictor of LF. On multivariate analysis, only stage ≥pT3-4 and nodes removed (<10) were significant independent predictors of LF with hazard ratios of 3.17 and 2.37 respectively (p<0.01). Analysis identified 3 patient subgroups with significantly different LF risk: low-risk (pT0-2), intermediate-risk (pT3-4, ≥10 nodes), and high-risk (pT3-4, <10 nodes) with 5-year LF rates of 8%, 23%, and 42% (p <0.01).

Conclusions: This study of local-regional recurrence risk factors after RC is based on the largest reported, prospectively maintained patient database with routine follow-up pelvic CT surveillance. LF after RC varies significantly among different subgroups. This risk stratification model could facilitate selection for future adjuvant radiotherapy trials.
Risk-adapted screening in bladder cancer using the open-access Internet-based questionnaire RiskCheck bladder cancer: First evaluation by the health services research foundation IQUO, Germany.
Authors: Luedecke Gerson , Geiges Goetz ,   Interessenverband zur Qualitätssicherung der Arbeit niedergelassener Uro-Onkologen in Deutschland e.V. \(IQUO\)
Published: February 2017

263

Background: Till this day urologists are waiting on symptomatic persons to initiate any diagnostic work-up to identify bladder cancer (BC) patients. In result we diagnose a quarter to a third of our patients as muscle-invasive cancers. The open-access questionnaire RiskCheck bladder cancer (RCBC) was proven in a pilot-study in daily routine from German urologists organized in the health services research foundation IQUO on asymptomatic patients.

Methods: The open-access RCBC questionnaire was used in urological offices to check asymptomatic patients for their BC risk exposure (personal, smoking, occupation and medical induced). The tool delivers the classical risk stratification in low- intermediate- and high risk. All people with intermediate and high risk were checked for tumor presence by urine diagnostics and in case of suspect results controlled by cystoscopy. Statistical analysis was made by IBM-SPSS 19 for incidence distribution and correlation between risk stratification and tumor detection was proven by classification tree analysis, significance p < 0.05.

Results: Out of 196 checked asymptomatic persons 185 (93.4%) were negative for tumor and 11 had a detectable tumor. In the group of NED 125 (68.1%) persons were classified as low risk, 26 (15.7%) as intermediate and 30 (16.2%) as high risk. Out of the 11 detected tumors 9 were at intermediate or high risk (81.8%). This resulted in an over all detection rate of 5.6% and focused on the risk population of 13.2%. The association of tumor presence and increased risk was significant (p < 0.01). Compared to the western incidence rates this is an increase in effectiveness of 377.

Conclusions: Risk-adapted screening in bladder cancer delivers a reasonable approach to diagnose bladder cancer before emerging symptoms. The questionnaire RCBC integrates evidence based bladder cancer inductors, is easy in use and as a open-access tool available in 10 languages via the Internet ( www.riskcheck-bladder-cancer.info) .
Phase Ib/II study of eribulin mesylate administered in combination with gemcitabine/cisplatin as first-line therapy for locally advanced or metastatic bladder cancer: Phase Ib results.
Authors: Vogelzang Nicholas J. , Conkling Paul , Duran Ignacio , Maroto José Pablo , Modiano Manuel , De Leonardis Piero , Hodge Jeff Paul , Lieberman Ronald
Published: February 2017

273

Background: Eribulin mesylate (E) is a synthetic analog of the natural, marine-sponge product halichondrin B. A phase (Ph) II study of E monotherapy in urothelial carcinoma with no prior cytotoxic therapy for advanced disease reported an overall response rate of 38% (95% CI: 23%, 54%; Quinn et al ASCO 2010, abstract 4539). Therefore, we combined E with gemcitabine (G) and cisplatin (C) to assess the feasibility, safety, and preliminary activity of the combination, in patients (pts) with advanced bladder cancer. This is an open-label, multicenter study consisting of a Ph Ib and Ph II portion.

Methods: In the Ph Ib portion, three ascending doses of E were to be administered IV on days 1 and 8 q21d to determine the MTD with standard doses of G (1000 mg/m2, days 1 and 8 q21d) and C (70 mg/m2, day 1). In Ph II, pts are randomized 1:1 to E plus G/C, or G/C alone.

Results: Nine pts (median age: 59 years; 7 male/2 female) entered Ph Ib. Pts received E 0.7 mg/m2 (n=3) or 1.0 mg/m2 (n=6), with standard dose G/C. Thirty-four cycles were given (2 pts are ongoing). One dose-limiting toxicity (DLT) was observed at 1.0 mg/m2 (Gr 4 thrombocytopenia). The 1.4 mg/m2 dose of E was not explored due to an investigator consensus that, with that dose, the probability of DLTs (severe hematologic toxicity) developing was high. Thus, the MTD was not achieved or defined. The recommended Ph II dose (RP2D) of E in combination with G/C was established as 1.0 mg/m2. Most common adverse events at the RP2D were nausea (83%), neutropenia (83%), fatigue (83%), thrombocytopenia (83%), anemia (83%), and anorexia (50%). Best responses at 1.0 mg/m2 were 1 complete response (CR) (unconfirmed) and 4 partial responses (PR) (all confirmed). Overall response for both cohorts was 89% – 2 CRs (1 confirmed, 1 unconfirmed) and 6 PRs (4 confirmed, 2 unconfirmed). Six pts have been randomized into the Ph II portion of the study to date.

Conclusions: E combined with standard G/C chemotherapy is feasible and has encouraging clinical activity. Hematologic toxicity is the main limiting factor.
Association of tumor hypoxia with lower survival after radiotherapy for muscle-invasive bladder cancer.
Authors: Tolan Shaun P. , Thoms John , Dal Pra Alan , Ahmed Omer , Chung Peter W. M. , Warde Fiona , Zlotta Alexandre , Evans Andrew , Bristow Robert Glen , Milosevic Michael
Published: February 2017

292

Background: Hypoxia may influence clinical outcomes in many human tumors, including muscle invasive urothelial carcinoma (UC) of the bladder. Hypoxia inducible factor-1 (HIF1), glucose transporter protein-1 (GLUT1) and carbonic anhydrase IX (CAIX) are all upregulated by hypoxia. This study examined the relationship between biomarkers of hypoxia or proliferation (Ki67) and clinical outcome in UC patients treated with radiotherapy (RT).

Methods: 70 patients were treated with curative intent using RT alone or RT plus neoadjuvant or concurrent chemotherapy (RTCT) between 1997 and 2006. Archived, paraffin-embedded, transurethral biopsy material was available for 44 patients (35 men and 9 women). Tumor was clinically confined to the bladder wall (cT2) in 28 patients and involved perivesical tissues or adjacent organs (cT3/T4) in 16. Tissue micro-arrays were constructed and immunohistochemical analyses performed to assess biomarker expression, which was scored independently by 3 observers in a semi-quantitative manner. The biomarker scores were correlated with clinico-pathologic data extracted from the medical record and with patient outcome. Median follow-up was 4.2 years.

Results: HIF1, GLUT1 and CAIX expression was seen in 43%, 96% and 65% of tumors respectively. The median Ki67 expression was 60%. There were no correlations between biomarkers expression and clinico-pathologic prognostic factors. The cystoscopic complete response rate was 71% at 2-3 months post-RT. The 4-year actuarial local control (LC) and overall survival (OS) rates were 48% and 55% respectively. High Ki67 expression was strongly predictive of better LC by univariate and multivariate analyses (70% vs 20% at 4 years, HR 0.95, p= 0.002), whereas no hypoxic marker predicted LC. High CAIX expression was predictive of inferior OS by multivariate analysis (HR 1.6, p=0.04).

Conclusions: Tumor hypoxia influences the outcome of patients with bladder cancer treated with RT or RTCT and is a potential therapeutic target. High Ki67 has been reported previously to be a marker of sustained LC in the bladder following RTCT but the biologic mechanism underlying this association is unknown and requires further investigation.
Incidence of peritoneal carcinomatosis in recurrent plasmacytoid urothelial carcinomas (PUC) of the bladder: A retrospective analysis of patient outcomes at M. D. Anderson Cancer Center (MDACC).
Authors: Dayyani Farshid , Munsell Mark F. , Siefker-Radtke Arlene O.
Published: February 2017

297

Background: PUC are a rare subset of urothelial cancers with a paucity of available literature regarding their clinical behavior.

Methods: Retrospective analysis of outcomes among all patients (pts) with predominant PUC (pPUC) seen at MDACC from 1999-2010.

Results: 31 pts with pPUC histology were identified (median age:63.5yrs; 83.3% male; TNM stage:cT1N0,n=4;cT2N0,n=8;cT3b-4aN0,n=6; cT4b, N+ or M+ n = 13). Median survival for all pts was 17.7mo (Stage I-III vs IV: 38.1 vs 13.3mo). Of 18 pts with potentially surgically resectable PUC (<=pT4aN0M0) 7 received neoadjuvant chemotherapy,10 had initial surgery, and one was treated with TURBT alone. Despite pathologic downstaging in 67% of pts treated with neoadjuvant chemotherapy relapses were common and there was no difference in survival between pts treated with neoadjuvant chemotherapy compared to initial surgery, even though adjuvant chemotherapy was given in 7 patients. Only 1 pt in pCR remains in remission >18 mo after surgery. The most common site of recurrence was in the peritoneum (13/18pts), with relapses occurring even in those with pCR at surgery. At least 4 pts developed CNS involvement with lepto-meningeal disease. In pts presenting with metastatic disease who were treated with chemotherapy, the median survival was 12.6 months.

Conclusions: Plasmacytoid bladder tumors are a very aggressive subset with overall poor outcomes. Though chemotherapy sensitive with downstaging seen with neoadjuvant chemotherapy, there are few long-term survivors. There is a strong predilection for recurrences along the peritoneal lining, and peritoneal carcinomatosis should remain high on a clinician’s differential when patients develop obstructive bowel symptoms.
Trends in metastatic bladder cancer incidence and prognosis by histologic subtypes.
Authors: Koll Thuy , Fang Xiang , Subbiah Shanmuga
Published: February 2017

322

Background: Approximately 5% of patients present with metastatic bladder cancer (MBC) at diagnosis.We aim to assess the trends of MBC at presentation over the last two decades using the Surveillance, Epidemiology, and End Results (SEER) database.

Methods: Retrospective analysis of MBC patients at presentation was done using data from SEER for 1988-2003. Age, Sex, Histology, Race, use of palliative surgery and survival data was extracted.

Results: 9357 patients with MBC were identified. Incidence of MBC remained same in the last 2 decades (6.05% vs 6.34%). The most common histology was (TCC) transitional cell with least common being Signet cell. Squamous cell carcinoma (SCC) was common in African Americans and in females. Common grade at presentation was poorly differentiated. Palliative surgery was done in 18.15% patients with radical cystectomy being the common type of surgery. Median survival was better in TCC with the worst outcomes in patients with SCC (Table).

Conclusions: Incidence of MBC at presentation hasn’t changed over the last two decades with TCC being the most common type. Clinical trials integrating targeted therpy with chemotherapy is needed to improve outcomes of MBC patients.

[Table: see text]
Relapses in metastatic germ-cell tumors and relationship to international guidelines compliance: A study from the Institut Gustave Roussy.
Authors: Thibault Constance , Loriot Yohann , Barrios Gonzales Daniel , Massard Christophe , Di Palma Mario , Bossi Alberto , Blanchard Pierre , Escudier Bernard J. , Patard Jean Jacques , Baumert Herve , Fizazi Karim
Published: February 2017

323

Background: Germ-cell tumors (GCT) are rare but highly curable cancers even in patients with metastatic spread. We aimed at assessing whether relapse after upfront treatment could be explained by low compliance with international guidelines.

Methods: All patients (pts) who were referred to Institut Gustave Roussy from 2000 to 2010 with progression or relapse after treatment for metastatic GCT were included. International guidelines available at the time of diagnosis were used as reference. A list of noncompliant criteria defined as disagreement with the recommendations with a potential impact on outcome was set up.

Results: 78 pts were included. According to the IGCCCG classification, 18 pts (23.1%) had good, 25 pts (32%) had intermediary and 34 pts (43.6%) had poor prognosis. The first-line chemotherapy administered consisted of PEB regimen (70.5%) , PE regimen (15.4%) or other regimen (12.8%). Most patients were treated in cancer centers (52.5%, n=41), whereas 26.9% and 17.9% pts were treated in private or public general hospitals, respectively. Only 50% pts received treatment according to guidelines recommendations. This percentage was significantly higher in cancer centres than in public hospitals (75.6% versus 28.6%, p< 0.001) or also when compared with private hospitals (75.6% versus 14,3%, p<0.001). The most frequent noncompliance criteria were: time to surgery for residual mass (over 6 weeks after the latest chemotherapy cycle)(20.3%) and respected chemotherapy schedule (20.3%). Other noncompliance findings were: inadequate chemotherapy dose (15.6%), number of cycles (12.5%), decision regarding residual disease (12.5%), chemotherapy regimen (6.3%), follow up (4.6%), type of surgery (3.1%), staging(1.6%), IGCCCG classification (1.6%), or decision regarding chemotherapy after residual mass surgery (1.6%).

Conclusions: This study suggests that the majority of relapse for metastatic GCT may be explained by a poor conformity to international guidelines and not only by aggressive tumor biology. These data represent a strong argument for treatment centralization in reference centers in patients with GCT.
Advanced urethral carcinomas: A retrospective analysis of survival outcomes and the role of cisplatin-based chemotherapy—The M. D. Anderson experience.
Authors: Dayyani Farshid , Pettaway Curtis A. , Kamat Ashish M. , Munsell Mark F. , Pagliaro Lance C.
Published: February 2017

330

Background: Primary carcinomas of the urethra (PCU) are rare and often advanced when diagnosed. Given the low incidence of this disease, there is a paucity of data regarding treatment standards. The purpose of this report was to study the treatment response and survival in a relatively large cohort of patients with PCU, with emphasis on modern platinum-containing chemotherapy regimens, in combination with surgery for (locally) advanced PCU.

Methods: We performed a retrospective chart review of consecutive patients with PCU seen at the MD Anderson Cancer Center over a recent 5-year period (2005-2010). Clinical outcome was measured as best response to chemotherapy (either neo-adjuvant or for metastatic disease). Kaplan-Meier estimates were generated for survival and Cox proportional hazard was used for prognostic factors for survival.

Results: We identified 44 consecutive pts with PCU. The majority (64%) were female, and the median age at diagnosis was 66.5 yrs. Squamous cell carcinoma and adenocarcinoma were the most common histologic subtypes of PCU in our cohort. 43% and 16% presented with lymph node–positive (LN+) and distant metastases, respectively. For all evaluable pts, the overall survival (OS) was 31.7 mo. Platinum-containing neoadjuvant chemotherapy achieved a response rate of 72%. 21/44 pts had locally advanced or LN+ PCU and were treated with chemotherapy followed by surgery. In this cohort, the median OS from chemotherapy initiation was 25.6 months. Among pts with LN+ PCU at diagnosis, 4/9 (44%) were alive as of July 2011, with a minimum follow-up of >3 years.

Conclusions: We report the clinical outcomes in the to the best of our knowledge largest cohort of consecutive pts with PCU. Our data suggests that modern platinum-containing regimens are effective in a subset of advanced PCU. Neoadjuvant treatment leads to prolonged disease-free survival in a substantial proportion of lymph node positive cases.
Pilot study on the correlation of multiphoton microscopy of human testicular tumors with histology.
Authors: Najari Bobby B. , Ramasamy Ranjith , Sterling Joshua , Aggarwal Amit , Sheth Seema , Jain Manu , Robinson Brian D. , Shevchuk Maria M. , Shariat Shahrokh F. , Mukherjee Sushmita , Scherr Douglas
Published: February 2017

338

Background: Partial orchiectomy is becoming more accepted for indications such as a solitary testis, and small nonpalpable testicular masses found incidentally on scrotal ultrasonography. Unfortunately, intraoperative frozen-section pathological analysis is often unable to accurately predict the presence of malignancy. Multiphoton microscopy (MPM) enables in vivo imaging of tissue without the use of labeling techniques and could potentially diagnose testicular tumor pathology. We performed a non-randomized, non-controlled study to evaluate the feasibility of MPM to image testicular biopsies.

Methods: Two men with testicular masses underwent radical orchiectomy for primary testicular tumor from June to August 2011. A total of six specimens from testicular tumor and uninvolved testes were imaged with MPM. In order to assess the diagnostic accuracy of MPM, we performed a blinded assessment by three uropathologists. The diagnosis rendered based on these images was then correlated with the findings seen on hematoxylin and eosin (H&E) staining.

Results: Our diagnosis based on MPM correlated with H&E in five of six (83%) specimens. Images of seminoma acquired with the MPM are easily distinguished from those of teratoma and normal testicular parenchyma. Images of seminoma show abnormal architectural and cellular changes compared to cystic structures often seen with teratoma.

Conclusions: Multiphoton microscopy can be used to reliably differentiate between teratoma, seminoma and normal testis tissue in our pilot group. MPM imaging could be potentially applied in intra-operative diagnosis of testicular tumors especially in testis-sparing surgery. Additional imaging of non-seminomatous germ cell tumors and non-germ cell tumors need to performed to verify the ultimate role of this technology.
The University of Southern California penile cancer experience: Clinicopathologic characteristics of patients from 1991 to 2011.
Authors: Jayaratna Isuru Sampath , Schwartz Rachel L. , Mitra Anirban Pradip , Cai Jie , Ma Yanling , Quinn David I. , Dorff Tanya B. , Schuckman Anne
Published: February 2017

342

Background: Penile squamous cell carcinoma (PSCC) is a disfiguring and deadly disease. USCS data has shown an increased incidence in specific US minority communities.

Methods: After IRB approval, a retrospective review of patients treated for PSCC at LAC-USC Medical Center, USC University Hospital, and Norris Comprehensive Cancer Center from 1991 to 2011 was completed. Patient characteristics were evaluated with descriptive statistics and contingency analyses.

Results: Of 69 patients identified with PSCC, 64 had surgical staging information available. Median follow up was 18 months (range 0 – 161). Median age at diagnosis was 50 (range 23–86), with 50.7% of patients ≥50 and 49.3% <50 at diagnosis. Hispanic patients represented 71% (n=44) of our cohort. 44 patients underwent partial penectomy, 10 total penectomy and 8 had [1]a diagnostic biopsy. T stage distribution was Tis: 7.8% (n=5), T1: 39.1% (n=25), T2: 29.7% (n=19), T3: 18.8% (n=12), T4: 1.6% (n=1) and unknown: 3.1% (n=2). 38 groins were surgically evaluated, and 14 pelvic lymph node dissections were performed. Of the 24 patients who underwent a surgical lymph node evaluation. The N stage distribution was N1: 41.7% (n=10), N2: 12.5% (n=3) and N3: 45.8% (n=11). Median lymph node yield in groin dissections was 11, with a lymph node positivity rate of 49%. 30.8% (n=20), 41.5% (n=27), 12.3% (n=8) and 15.4% (n=10) of patients had well, moderately, poorly differentiated PSCC or unknown grade, respectively. There was no association of age (p=0.16) or race (p=0.24) with clinical stage. Stage was significantly associated with grade (p=0.049), with 75% of poorly differentiated tumors being Stage 4, compared with 21.4% of well-moderately differentiated tumors.

Conclusions: In our cohort, we found a primarily Hispanic ethnic prevalence, which is reflective of our patient population, as well as a younger age at diagnosis in contrast to previously published reports. We observed a higher average stage in both T and N stages in our population compared with national averages. It is noted that the small sample size limits our power to draw conclusions, however this initial description of our population suggests variation in the disease process that may be related to demographic factors.
Response of the human kidney to clamp ischemia.
Authors: Ercole Barbara , Torkko Kathleen , Hilton William , Venkatachalam Manjery A. , Weinberg Joel M. , Parekh Dipen J.
Published: February 2017

365

Background: Structural changes in tubule cells during clamp ischemia are well characterized for animal models, but their timing and extent in the human kidney has not been established and may differ significantly. To better define the human response, we biopsied uninvolved areas of kidney in patients undergoing open partial nephrectomy for renal masses.

Methods: Biopsies of 40 patients undergoing PN were obtained at specified time intervals: before renal artery clamping, then during periods ranging from 15 to 60 min. of warm and cold ischemia (80% > 30 min.), and then after 5 minutes of reflow. These biopsies were assessed for ultrastructure (N=39) and for immunofluorescence and rhodamine phalloidin staining (N=22).

Results: During the clamp period, apical membrane structure was remarkably well preserved with only patchy brush border clubbing, fragmentation, desquamation and blebbing and not in all patients. Mitochondria developed progressive swelling, which paradoxically was more prominent in distal than proximal tubule cells. This resolved during the 5 minutes of reflow in most cells in most patients, but persistence of swelling and development of matrix condensation occurred occasionally. Using a composite 0-5 scale covering the full spectrum of ultrastructural changes, average scores were: Preclamp 1.02±0.07, End clamp 2.18±0.07, Post clamp 1.86±0.09. Consistent with the ultrastructure, staining for F-actin with rhodamine phalloidin was well preserved. Immunsotaining for phosphotyrosine, which reflects cellular ATP content was decreased in 68.4% of the clamp biopsises and 52.6% of the postclamp biopsies with larger changes in proximal tubules, however B1 integrin was decreased in only one post clamp biopsy. ICAM-1 expression in peritubular capillaries was increased in 46.7% of the clamp biopsies and 66.7% of post clamp biopsies. None of the patients developed acute kidney injury.

Conclusions: These data provide the first detailed analysis of the structural response of the human kidney to clamp ischemia and document many of the expected structural alterations based on prior animal work, but indicate a greater than expected resistance to injury in this commonly used clinical application of clamp ischemia.
Pretreatment (pre-tx) neutrophil to lymphocyte ratio (NLR) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with ketoconazole (keto): Association with outcome and predictive model.
Authors: Keizman Daniel , Ish-Shalom Maya , Maimon Natalie , Gottfried Maya , Carducci Michael Anthony , Eisenberger Mario A. , Sella Avishay
Published: February 2017

37

Background: The CYP17 inhibitor Keto is active in mCRPC. The NLR, an index of systemic inflammation, is associated with prognosis in several types of cancer. We assessed the association between pre-tx NLR and outcome of mCRPC pts treated with keto.

Methods: We performed a multicenter retrospective study of pts with mCRPC, who were treated with keto. We analyzed the pre-tx NLR and previously described factors associated with keto tx outcome as prior response to hormonal tx, pre-tx PSADT, and extent of metastatic disease (limited-axial skeleton/nodal vs extensive- appendicular skeleton/visceral). Progression free survival (PFS) was determined by the Kaplan-Meier method. Multivariate analyses using Cox regression model were performed to determine their independent effect, and to form a predictive model. A survival tree analysis was used to find the best NLR cut-off value.

Results: From 1999-2011, 135 mCRPR pts were treated with keto. 67/135 (50%) had ≥ 50% PSA decline. Overall median PFS was 8 months (mos) (range 1-134 ). Excluded from the analysis were pts without available data on pre-tx NLR (n=8), and those with recent (≤1 mos) health event (surgery, n=1) or tx (steroids, n=3 or radiation, n=3) known to be associated with a change of blood counts. 120 pts were included in the analysis. 57 (48%) had an elevated pre-tx NLR >3. Risk factors associated with PFS (table) were pre-tx NLR >3, prior response to GnRH-a <24 mos and to AA <6 mos, and pre-tx PSADT <3 mos. The number of risk factors was used to categorize patients into three risk groups (table): favorable (0-1 factors), intermediate (2 factors), and poor (3-4 factors).

Conclusions: In mCRPC pts treated with keto, pre-tx NLR, prior response to hormonal tx, and pre-tx PSADT are associated with PFS, and may be used to categorize pts into risk groups.

[Table: see text]
Phase I/II study of a BNC105P/everolimus regimen for progressive metastatic renal cell carcinoma (mRCC) following prior tyrosine kinase inhibitors (Hoosier Oncology Group).
Authors: Hutson Thomas E. , Dang Long H. , Lauer Richard C. , Starodub Alexander , Hauke Ralph J. , Logan Theodore , Bylow Kathryn A. , Galsky Matt D. , Bibby David C. , Kremmidiotis Gabriel , Doolin Elizabeth E. , Lavranos Tina C. , Leske Annabell F. , Hahn Noah M. , Sonpavde Guru , Sweeney Christopher , Sarantopoulos John ,   Hoosier Oncology Group
Published: February 2017

373

Background: BNC105P is a Vascular Disruption Agent (VDA) that destabilizes tubulin polymers leading to selective damage of tumor vasculature, hypoxia and associated tumor necrosis. BNC105P also has a direct anti-proliferative action on cancer cells. Up regulation of the mTOR pathway has been identified as a survival response by the tumor to hypoxic insult. Preclinical investigations demonstrated that BNC105P is effective at selectively damaging the vasculature in primary and metastatic lesions. Furthermore, BNC105P monotherapy compared well with sunitinib in mice bearing kidney tumors. It follows that the combined use of this VDA with an agent active against mTOR may improve clinical outcome in patients with progressive mRCC who are refractory to tyrosine kinase inhibitors (TKI).

Methods: A phase I/II study in mRCC patients who have received 1-2 prior TKIs was undertaken. Using a classic 3+3 design, the phase I component of this study enrolled 12 subjects at 4 dose levels of BNC105P (4.2, 8.4, 12.6 and 16 mg/m2; IV infusion Days 1 & 8, 21-day repeating cycle). Everolimus was administered concurrently (10 mg p.o.). PK analysis was performed during Cycle 1.

Results: In the clinic the BNC105P / everolimus combination was well tolerated and no DLTs were observed in any of the phase I patients. Toxicities deemed to be drug-related included single events of Grade 2 anemia, thrombocytopenia and mucositis. Of the 12 patients enrolled to the phase I, 7 remain on treatment. The medium number of cycles is 3 (range: 1–14) and 3 patients have been administered >6 cycles of treatment. The randomized phase II component of the study continues and will compare everolimus given in combination with BNC105P to a sequential approach (everolimus followed by BNC105P).

Conclusions: The MTD of BNC105P (16 mg/m2) can be combined with full dose everolimus and is being evaluated in the randomized phase II study.
Incidence of reduced penis size among men with recurrent prostate cancer previously treated with surgery, radiation plus androgen deprivation, or radiation alone.
Authors: Parekh Arti , Chen Ming-Hui , Hoffman Karen Elizabeth , Choueiri Toni K. , Hu Jim C. , Bennett Charles L. , Kattan Michael W. , Sartor A. Oliver , Stein Karen , D'Amico Anthony Victor , Nguyen Paul Linh
Published: February 2017

38

Background: The relative incidence of reduced penis size across prostate cancer treatment modalities is not well-known.

Methods: The incidence of physician-reported patient complaints about reduced penis size was calculated for 948 men in the COMPARE registry who experienced PSA failure and were assessed a median of 5.45 (2.6-8.9 IQ range) years after prostatectomy or radiation (RT) consisting of either external beam or brachytherapy. Multivariable logistic regression was used to determine factors associated with poorer sexual function and incontinence.

Results: Of 948 men, 25 (2.63%) complained of a reduced penis size. The incidence of reduced penis size by treatment was: surgery (19/510=3.73%), RT plus androgen deprivation therapy (ADT) (6/225=2.67%), RT without ADT (0/213=0%). Surgery (p=0.004) and RT+ADT (p=0.016) had significantly more short penis complaints than RT alone. Rates of shortened penis for surgery and for RT+ADT were similar (p=0.47). On multivariable analysis adjusting for age and treatment type, short penis was associated with poorer sexual function (Odds ratio: 2.430, 95% CI: 1.046-5.643) (p=0.0389) and more incontinence (Odds ratio: 4.671, 95% CI: 1.985-10.994) (p=0.0004).

Conclusions: Complaints about reduced penis size were more common with RT+ADT or surgery than with RT alone, and were associated with poorer sexual function and incontinence issues.