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1506 Background: Hereditary breast and ovarian cancer (HBOC) is preventable when genetic risk is identified. We aimed to test whether pre and/or post-test genetic counseling is needed to optimally deliver online accessible genetic testing. Methods: MAGENTA (Making GENetic Testing Accessible) is a four-arm non-inferiority trial evaluating electronic genetic education and results delivery alone or combined with pre-test only, or post-test only telephone genetic counseling compared to mandatory pre- and post-test counseling (control arm) in women at risk of HBOC (NCT02993068). Regardless of assigned arm, all subjects with a pathogenic mutation received post-test telephone counseling. All subjects were enrolled electronically as part of either a family history cohort (FHC) or a cascade cohort (CC, known familial mutation). The primary outcome was cancer risk distress at 3 months and the trial was powered for the FHC. Secondary outcomes included completion of testing (i.e., received results), anxiety, depression, quality of life, and decisional regret, all measured by standardized scales. Results: Enrollment is complete and a total of 3,822 participants were randomized, 3,111 in FHC and 711 in CC. Participants were enrolled from all 50 states, but most were white/non-Hispanic (88%). Among participants that completed genetic testing, 173 (7.2%) had a mutation in a breast or ovarian cancer gene, with 114 (5.7%) of FHC and 59 (14.2%) of CC. In the primary intention-to-treat analysis of FHC, each of the three experimental arms was non-inferior to the control arm for distress at 3 months (p < 0.025/3 = 0.0083). In the CC, no and pre-test only counseling were also non-inferior (p < 0.025/3 = 0.0083). Distress was lowest in the arm with neither pre nor post-test counseling. Overall, 318 (18%) participants had very high distress at three month follow-up, and this rate was not significantly different across arms. Anxiety, depression and decisional regret did not have statistically significant differences across arms at follow-up. Test completion was highest in the no counseling arm (86.4%) and lowest in the control arm (60.6%). Conclusions: Electronic genetic education and results release without genetic counseling was non-inferior with regard to patient distress and was associated with higher test completion and lower distress. These results support use of a genetic testing paradigm providing individualized genetic counseling only for patients with positive test results. Clinical trial information: NCT02993068.

Purpose Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after matched unrelated, related, or mismatched related donor hematopoietic stem-cell transplantation (HSCT). Improved GVHD prevention methods are needed. Pentostatin, an adenosine deaminase inhibitor, leads to lymphocyte depletion with low risk of myelosuppression. We hypothesized that addition of pentostatin to GVHD prophylaxis with tacrolimus and mini-methotrexate may improve outcomes, and we conducted a Bayesian adaptively randomized, controlled, dose-finding study, taking into account toxicity and efficacy. Patients and Methods Success was defined as the patient being alive, engrafted, in remission, without GVHD 100 days post-HSCT and no grade ≥ 3 GVHD at any time. Patients were randomly assigned to pentostatin doses of 0, 0.5, 1.0, 1.5, and 2.0 mg/m2 with drug administered on HSCT days 8, 15, 22, and 30. Eligible patients were recipients of mismatched related (n = 10) or unrelated (n = 137) donor HSCT. Results Median age was 47 years. Thirty-seven, 10, 29, 61, and 10 patients were assigned to the control and four treatment groups, respectively, with comparable baseline characteristics. Pentostatin doses of 1.0 and 1.5 mg/m2 had the highest success rates (69.0% and 70.5%) versus control (54.1%). The posterior probabilities that the success rates were greater with 1.5 mg/m2 or 1.0 mg/m2 versus control are 0.944 and 0.821, respectively. Hepatic aGVHD rates were 0%, 17.2%, and 11.1%, respectively, for 1.5 mg/m2, 1.0 mg/m2, and control groups. No grades 3 to 4 aGVHD occurred in 11 HLA-mismatched recipients in the 1.5 mg/m2 group. Conclusion Pentostatin increased the likelihood of success as defined here, and should be further investigated in larger randomized, confirmatory studies.

Purpose To compare quality of life and sexual functioning in cervical cancer survivors treated with either radical hysterectomy and lymph node dissection or radiotherapy. Methods Women were interviewed at least 5 years after initial treatment for cervical cancer. Eligible women had squamous cell tumors smaller than 6 cm at diagnosis, were currently disease-free, and had either undergone surgery or radiotherapy, but not both. The two treatment groups were then compared using univariate analysis and multivariate linear regression with a control group of age- and race-matched women with no history of cancer. Results One hundred fourteen patients (37 surgery, 37 radiotherapy, 40 controls) were included for analysis. When compared with surgery patients and controls using univariate analysis, radiation patients had significantly poorer scores on standardized questionnaires measuring health-related quality of life (physical and mental health), psychosocial distress and sexual functioning. The disparity in sexual function remained significant in a multivariate analysis. Univariate and multivariate analyses did not show significant differences between radical hysterectomy patients and controls on any of the outcome measures. Conclusion Cervical cancer survivors treated with radiotherapy had worse sexual functioning than did those treated with radical hysterectomy and lymph node dissection. In contrast, these data suggest that cervical cancer survivors treated with surgery alone can expect overall quality of life and sexual function not unlike that of peers without a history of cancer.

Purpose To determine the efficacy and side effects of taxanes, with or without platinum, for the treatment of sex cord-stromal tumors of the ovary. Patients and Methods We conducted a retrospective review of all patients seen from 1985 to 2002 at The University of Texas M.D. Anderson Cancer Center with ovarian sex cord-stromal tumors. Eligible patients underwent pathology confirmation and clinical evaluation at M.D. Anderson and received a taxane for initial or recurrent disease. Results Of 222 patients identified, 44 were eligible for analysis. For nine patients treated in the first-line adjuvant setting, median progression-free survival (PFS) was not reached at 51 months. Of two patients treated for measurable disease in the first-line setting, one had a complete response. Median PFS was 34.3 months; median overall survival (OS) was not reached. Median follow-up was 90.3 months (range, 39.4 to 140.5 months). Response rate for 30 patients treated with a taxane ± platinum for recurrent, measurable disease was 42%. Median PFS was 19.6 months; median OS was not reached. Median follow-up was 100.7 months (range, 8.1 to 361.3 months). The presence of platinum correlated with response in the recurrent, measurable disease setting. The number of patients was insufficient to detect relative efficacy of paclitaxel and docetaxel. Adverse effects of paclitaxel included neutropenia (n = 6), anemia (n = 1), thrombocytopenia (n = 1), myelodysplasia (n = 1), and hypersensitivity (n = 1). Conclusion Taxanes seem to be active agents in the treatment of patients with sex cord-stromal tumors of the ovary. The combination of taxanes with platinum in the treatment of this disease deserves additional investigation.

Purpose Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer characterized by early metastasis, resistance to therapy, and a high mortality rate. Little is known about the biology of these tumors. Smaller studies suggest that Her-2/neu may be involved in the tumorigenesis of this disease. The purpose of this study was to evaluate the protein expression and gene amplification of Her-2/neu in UPSC and to determine its prognostic value. Patients and Methods Tumor tissue from 68 patients with UPSC treated at The University of Texas M.D. Anderson Cancer Center from 1989 to 2002 was available. Her-2/neu expression was evaluated by immunohistochemistry (IHC). Overexpression was defined as complete membrane staining in greater than 10% of the cells. In tumors with overexpression of Her-2/neu by IHC, fluorescence in situ hybridization (FISH) was performed to assess gene amplification. Clinical and pathologic information was obtained from medical records. Results Twelve (18%) of 68 tumors demonstrated Her-2/neu overexpression. Of these, only two showed gene amplification. When evaluating all 68 patients, Her-2/neu overexpression was associated with a poorer overall survival (OS; P = .008). In our multivariate Cox proportional hazards models, Her-2/neu IHC overexpression, lymph node status, and stage were each associated with OS (P ≤ .05). Conclusion Positive IHC overexpression of Her-2/neu was seen in 18% of UPSCs but was rarely correlated with Her-2/neu gene amplification. Overexpression of Her-2/neu was associated with a worse overall prognosis. The use of trastuzumab (Herceptin; Genentech, South San Francisco, CA) in women with UPSC should be further evaluated in a clinical trial setting.

Purpose To evaluate the efficacy of long-term nontunneled silicone catheters impregnated with minocycline and rifampin (M-R) in reducing catheter-related bloodstream infections. Patients and Methods This prospective, randomized, double-blind clinical trial was conducted at M.D. Anderson Cancer Center, a tertiary care hospital in Houston, TX. All patients in the trial had a malignancy. Results Between September 1999 and May 2002, 356 assessable catheters were used: 182 M-R and 174 nonimpregnated. The patients' characteristics were comparable between the two study groups. The mean (± standard deviation) duration of catheterization with M-R catheters was comparable to that of nonimpregnated catheters (66.21 ± 30.88 v 63.01 ± 30.80 days). A total of 17 catheter-related bloodstream infections occurred during the course of the study. Three were associated with the use of M-R catheters and 14 were associated with the nonimpregnated catheters, with a rate of catheter-related bloodstream infection of 0.25 and 1.28/1,000 catheter-days, respectively (P = .003). Gram-positive cocci accounted for the majority of the organisms causing the infections. There were no allergic reactions associated with M-R catheters. Conclusion Long-term nontunneled central venous catheters impregnated with minocycline and rifampin are efficacious and safe in reducing catheter-related bloodstream infections in cancer patients.

Purpose: To identify prognostic factors related to outcome in 219 children and adolescents with synovial sarcoma. Patients and Methods: We combined the experiences of the four following research groups: Cooperative Weichteilsarkomastudie Group, Germany (n = 95); St. Jude Children’s Research Hospital, Memphis, TN (n = 49); Istituto Nazionale dei Tumori, Milan, Italy (n = 33); and The University of Texas M.D. Anderson Cancer Center, Houston, TX (n = 42). Kaplan-Meier and Cox proportional hazard analyses were performed. Results: The median age at diagnosis was 13 years (range, 1 to 20 years), and the median follow-up was 6.6 years (range, 0.5 to 30.7 years). The estimated 5-year overall survival and event-free survival rates for the entire group were 80% ± 3% (SE) and 72% ± 3%, respectively. A previously unreported interaction between tumor size and invasiveness was observed that statistically significantly related to outcome. In multivarible analysis, patients with T1B and T2B disease (hazard ratio [HR] = 5.6, 95% confidence interval (CI), 1.9 to 16.2; and HR = 5.9, 95% CI, 2.1 to 16.4, respectively) or Intergroup Rhabdomyosarcoma Study (IRS) Clinical Group III and IV disease (HR = 2.7, 95% CI, 1.2 to 6.5; and HR = 14.1, 95% CI, 4.3 to 31.3, respectively) had poor overall survival. Treatment with radiotherapy was related to improved overall survival (HR = 0.4; 95% CI, 0.2 to 0.7). In IRS Group III patients, objective response to chemotherapy (18 of 30, 60%) correlated with improved survival. Conclusion: Clinical group, tumor size, and invasiveness are important prognostic factors. Multicenter randomized clinical trials are needed to determine both the effect of chemotherapy on survival and the necessity of local radiotherapy in patients with completely resected tumors.

5511 Background: Recent studies show that germline or somatic BRCA1/2 mutations and homologous recombination (HR) defects can be used to predict response to PARP inhibitors in recurrent ovarian cancer. However, the impact of defects in BRCA1/2 and HR genes on overall clinical outcomes are not yet defined for patients undergoing neoadjuvant chemotherapy (NACT) versus upfront surgical debulking (USD). Methods: Previously untreated ovarian cancer patients were prospectively enrolled under approved IRB protocol. Germline and tumor BRCA1/2 mutation testing and methylation were analyzed when sufficient tumor and blood was available. Mutation in 21 additional hereditary cancer genes (including HR genes) was also evaluated. Tumor HR defects were scored on LOH, telomeric allelic imbalance, and large-scale state transitions (as previously described). Presence of germline or somatic BRCA1/2 mutations, BRCA1 methylation, HR score ≥42, or germline mutation in other HR genes were defined together as HRD positive. Results: Of 299 enrolled patients, 129 (43%) received USD and 170 (57%) received NACT. Patients receiving USD had better outcomes compared to NACT, including overall survival (OS, 65.8 vs 45.2 months, p = 0.0003) and event free survival (EFS, 24.8 vs 15.6 months, p < 0.0001). In the overall cohort, EFS was significantly longer for HRD positive patients vs HRD negative (20.5 vs 16.3 months, p = 0.0268). Patients with somatic and germline BRCA1/2 mutations had longer OS vs BRCA1/2 negative (65.3 vs 46.1 months, p = 0.0403). Overall outcomes were worse in NACT compared to USD, but impact of BRCA1/2 mutations and HR defects was stronger in this group. NACT patients with any HR defect had longer EFS (19.7 vs 14.5 months, p = 0.0247). NACT patients with BRCA1/2 germline mutations had longer OS (65.3 vs 38.3 months, p = 0.0230). NACT patients with BRCA1/2 germline mutation had longer EFS (22.6 vs 14.6 months, p = 0.0047). OS and EFS in USD patients were significantly changed based on only debulking status; mutation or HR status did not have a statistically significant effect. Conclusions: While HR defects and BRCA1/2 mutations influence overall outcomes for ovarian cancer patients, the impact is stronger in NACT compared to USD.

5506Background: The combination of everolimus and letrozole has shown promising results in the treatment of recurrent endometrioid endometrial cancer (EEC). Both pre-clinical data and experience fr...

TPS5610Background: High grade serous ovarian cancer (HGSOC) is associated with DNA repair and cell cycle aberrations, such as mutations in p53, which result in G1/S checkpoint deficiencies and high...

104 Background: Symptoms reported by women with cervical cancer (CCx) include pain, fatigue, lymphedema, sexual dysfunction, proctitis, cystitis, constipation and diarrhea. The objective of this study was to delineate and measure the symptom distress experienced by patients with advanced CCx at the time of palliative care (PC) referral. Methods: A total of 156 advanced CCx patients were referred to PC from 2010 to 2012. Of these, 88 patients had completed the Edmonton Symptom Assessment System (ESAS) and were included in the analysis. Descriptive statistics were used to summarize the data. Results: At the time of presentation mean age was 45 (25-76), 47% were Caucasian, 18% African American, and 33% Hispanic. Fifty-one percent were married; 64% had no advance directives; 75% had recurrent disease. Clinically significant symptoms (defined as ESAS scores ≥ 4) were pain (81%), anorexia (72%), a poor feeling of well-being (70%), fatigue (69%), and insomnia (54%). The chief complaint was pain in 94% of patients. According to the PC specialists’ assessment, pain (96%), emotional distress (77%), and constipation (50%) were predominant symptoms. Various palliative care interventions including opioids, laxatives, and expressive supportive counseling were provided. The median time from advanced cervical diagnosis to PC consultation was 6.0 months (95% CI 5.0-7.8) and the median survival after first PC visit was 4.8 months (95% CI 3.4-6.2). Clinically significant symptoms including nausea, depression, anxiety, and feeling of well-being showed significant improvements at follow-up visits. Conclusions: More than half of patients with advanced CCx were significantly burdened with pain, anorexia, poor feeling of well-being, fatigue, insomnia, and constipation at the time of PC referral. Clinically significant symptoms showed improvements at follow-up visits. In patients with significant symptom distress, early PC involvement may be important to improve quality of life.

e16541 Background: Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) is a rare disease with fewer than 300 reported cases. Recent studies have shown association with a mutation in the S...

5584 Background: Omentin is a protective adipokine secreted by the mesothelial cells of visceral adipose tissue. Its expression is inversely related to obesity and low levels have been found to be ...

e16542 Background: SCCOHT is a rare and aggressive disease. Regardless of tumor stage, most patients relapse and die of disease within two years of diagnosis. However, a small proportion of patient...

5512 Background: Screening for Lynch Syndrome (LS) in endometrial cancer (EC) has traditionally been based on early age at diagnosis and family history. Universal tumor testing has been proposed gi...

5510 Background: Metformin reduces cancer incidence and improves overall survival in diabetic patients. Preclinical studies have shown that metformin decreases endometrial cancer (EC) cell growth b...

4528 Background: The role of cisplatin-based chemotherapy for the treatment of locally advanced or metastatic urothelial carcinoma is well established. For patients (pts) who cannot receive cisplatin owing to renal insufficiency, substitution with carboplatin was associated with inferior response rate and overall survival (OS). To address this unmet need, we conducted a phase II study of gemcitabine (Gem), paclitaxel (Tax), and doxorubicin (Adria) in this group. Methods: The primary endpoint was overall response rate (ORR); secondary endpoints were toxicity, OS, and the safety and efficacy of pegfilgrastim 6 mg (G-CSF) given immediately after chemotherapy on Day 1. A Simon 2-stage design was chosen to detect ORR of 40% and to reject ORR of 25%. Eligible pts had metastatic or unresectable urothelial carcinoma, no prior chemotherapy, performance status ≤ 2, glomerular filtration < 60 ml/min, and no need for dialysis; all gave informed consent. Brain metastases were excluded, as were clinically significant heart disease, peripheral neuropathy, and liver or bone marrow dysfunction. Treatment consisted of 900 mg/m2 Gem (fixed rate of 10 mg/m2/min), 135 mg/m2 Tax, and 40 mg/m2 Adria administered with same-day GCSF every 14 d to a maximum of 9 cycles. Tumors were evaluated after every 3 cycles. Results: Forty pts were enrolled January 2008 through November 2011, and 39 could be assessed for response. Median age was 72 (range, 51–89) and 11 pts (28.2%) were women. There were 7 complete and 15 partial responses, for an ORR of 56.4% (95% CI 39.6-72.2). Notable grade 3 and 4 nonhematologic toxicities in the first 2 cycles were dyspnea and mucositis (1 pt each). There were no treatment-related deaths and no toxicity attributed to same-day G-CSF. Median OS was 14.4 mo with median follow-up of 12.6 mo for all pts, 15.6 mo for 10 who were alive. Conclusions: Gem-Tax-Adria is effective as first-line treatment for metastatic or locally advanced urothelial carcinoma, and it can safely be given to pts with renal insufficiency. Same-day G-CSF also appears to be safe and effective in this setting. Phase III study is warranted. Clinical trial information: NCT00478361.

5596 Background: Advanced-stage (III/IV) uterine papillary serous carcinoma (UPSC) has a median overall survival (OS) of ~ 3 yrs. The study objective was to determine factors associated with long-term survival in advanced stage UPSC. Methods: We performed a retrospective review of pts diagnosed with stage III or IV UPSC between 1993 and 2012. Summary statistics were used to describe demographic and clinical characteristics. OS was estimated with the Kaplan-Meier estimator. Fisher’s exact test and the Wilcoxon rank sum test were used to compare pts surviving >3 yrs with those surviving 3 yrs was 0.462, >4 yrs was 0.310, and >5 yrs was 0.228. Thirty-six (14%) pts survived >3 yrs and 37 (14%) survived 3 yrs compared to pts surviving

TPS6100 Background: BRAF mutations are found in 40% of pts with newly diagnosed PTC but much more prevalent in recurrent PTC, ranging from 78-86%, suggesting they play an active role in tumor progression. Activating mutations in BRAF result in constitutive activation of MEK and subsequently ERK. ERK mediates activation of nuclear transcription factors coordinating expression of genes involved in proliferation and survival of malignant cells. PTC usually has an excellent prognosis, especially in younger pts and in pts who respond to the only effective treatment: surgery followed by radioactive iodine (RAI). However, more advanced stage disease at diagnosis, older age, and lack of RAI avidity are associated with a high rate of recurrence and distant metastasis, imparting a worse overall survival. Long-term outcomes depend highly on initial surgery outcome. Pts at highest risk of recurrence and death are those with gross residual disease after surgery and macroscopic tumor invasion. VEM is an inhibitor of the activated form of the BRAF serine-threonine kinase enzyme. The drug is FDA approved for the treatment of advanced melanoma and is currently being studied in a phase 2 trial in metastatic BRAF-mutated PTC. This is a neoadjuvant trial to determine if pharmacodynamic changes in the tumor correlate with response to drug. Methods: Pts with primary or recurrent BRAF mutated PTC who are planned for surgical resection are eligible. Pts will undergo baseline core biopsy prior to starting VEM 960mg bid. After 56 days of treatment they will undergo surgery and post-treatment specimen will be collected. Pts with widely metastatic PTC may continue VEM. The primary endpoint is to determine whether changes in ERK phosphorylation responses after treatment with VEM correlate with clinical response at day 56 in pts with locally advanced, BRAF mutated PTC. Secondary endpoints include assessments of safety of neoadjuvant VEM, response by RECIST, rate of surgical complications, persistent disease at the surgical site at 1 year, and mechanisms of resistance to VEM. The trial began enrolling pts in December 2012, with a total of 22 pts planned. This trial has no sponsor. Clinical trial information: NCT01709292.

9061 Background: Although great progress has been made in the control of chemotherapy-induced vomiting (CIV), prevention of chemotherapy-induced nausea (CIN) has been less successful. Preliminary data suggests that some families of lesser used antiemetic agents, such as the cannabinoids, may have greater efficacy against nausea than against vomiting. Methods: Adult solid tumor patients (pts) receiving cyclophosphamide ≤ 1500 mg/m2 (C) and/or doxorubicin ≥ 40 mg/m2 (A) were eligible. Pts could have received prior mildly emetogenic chemotherapy (EC). Pts were not eligible who were receiving other moderately or highly EC, were receiving cranial, abdominal or pelvic radiotherapy, had CIV/CIN with previous chemotherapy, had other causes for nausea/vomiting besides chemotherapy, or were scheduled to receive other antiemetics. Pts with habitual cannabinoid use were not eligible. All pts received palonosetron 0.25 mg (PALO) and dexamethasone 10 mg (DXM) IV before chemotherapy. Patients were randomized double-blind to receive dronabinol 5 mg (D) or matching placebo (P) 3 times a day for 5 days. Nausea, vomiting and toxicity data was collected daily for 5 days. Results: 62 pts were entered on study – female/male 61/1, White/Black/Hispanic/Other 45/14/2/1, median age (range) 58 (29-76). No significant difference was noted in CIV-dependent endpoints (including No Vomiting, Complete Response, or Complete Protection) or in rescue medication use. However pts receiving D had a shorter duration of nausea – Mean number of days of nausea (D vs P) 1.86 days vs 3.10 days (p=0.027) – and a trend toward greater frequency of No Nausea (D vs P) 37% vs 17% (p=0.143). Common toxicities included fatigue (D/P 17/11), headache (D/P 16/16), dizziness (D/P 14/7), constipation (D/P 14/11), and diarrhea (D/P 13/6) No pt discontinued therapy due to mood changes. Conclusions: Low-dose D decreased the duration of CIN and increased the frequency of No Nausea in pts receiving C and/or A. Agents to prevent CIV (such as PALO and DXM) and to prevent CIN (such as D) have complementary activity and result in improved overall control when used together.

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.

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 (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.

254 Background: The addition of bevacizumab to capecitabine-based chemoradiotherapy (CRT) for LAPC has been shown to be safe. The aim of this study was to determine the safety, tolerability and maximum tolerated dose (MTD) of the addition of erlotinib to this treatment regimen. Methods: Seventeen patients with CT-staged biopsy-proven non-metastatic unresectable LAPC were enrolled between March 2008 and October 2010. Prior chemotherapy was permitted. All patients received 50.4 Gy (GTV only) in 28 fractions with concurrent capecitabine, bevacizumab and erlotinib. Dose was escalated using a continual reassessment method. Two patients each were enrolled at dose levels (DLs) 1-4 and 9 patients at DL 5. Bevacizumab was escalated from 5mg/Kg every two weeks (DLs 1-4) to 10mg/Kg (DL 5); erlotinib from 100 mg/day (DLs 1-2) to 150 mg/day (DLs 3-5); and capecitabine from 400mg/m2 twice daily on days of radiation (DL 1) to 600mg/m2 (DLs 2-3) to 825 mg/m2 (DLs 4-5). Reassessment for potential resection was performed 6-8 weeks later. Results: With a median follow-up of 10 months (range 3-23), no grade 3 toxicities were observed in DLs 1-4. Three (33%) patients at DL 5 developed a grade 3 acute toxicity (2 diarrheas and 1 rash). No grade 4 or 5 toxicities were seen. DL 4, with a posterior probability of 0.122 of dose limiting toxicity, was selected as the MTD. Median survival was 19.4 months and time to distant progression was 9.8 months. Patients treated at DLs 4 and 5 had a median survival of 24 months. Of 5 patients who underwent margin-negative resections, 4 were originally deemed unresectable and 1 was borderline; 4 were treated at DLs 4 or 5 (36% of patients treated at these DLs); 3 patients had excellent pathological responses (complete response, 5% viable tumor, and 20% viable tumor) at pancreatectomy and are alive at 13, 21 and 22 months respectively with no local or distant failures. Conclusions: The combination of erlotinib, bevacizumab and capecitabine with radiotherapy for LAPC is safe and tolerable. Both the promising survival and the high rate of resectability at the higher dose levels suggest that this strategy of dual inhibition of growth factor receptor pathways during CRT warrants continued evaluation.

544 Background: The goal of this phase I trial was to determine the maximal tolerated dose (MTD) of concurrent capecitabine, bevacizumab and erlotinib with preoperative radiation therapy (RT) for rectal cancer, with a secondary objective of evaluating pathologic complete response (pCR). Methods: Eligibility criteria included patients with clinical stage II-III rectal adenocarcinoma within 12 cm from the anal verge. Exclusion criteria included uncontrolled hypertension, recent myocardial infarction or angina, coagulopathy, impaired renal function, and history of gastrointestinal perforation. Patients were treated in cohorts of 2, in 4 escalating dose levels (DL), using the continual reassessment method, as shown in the table. Patients underwent surgery at least 9 weeks after the last dose of bevacizumab. Results: Nineteen patients were enrolled in the study: 1 withdrew early because of insurance issues and was non-evaluable. The clinical stage was T3N0 in 3, T3N1 in 13, T3N2 in 1 and T4N0 in 1 patient. No patient had grade 4-5 acute toxicity; 1 patient had grade 3 acute toxicity (hypertension, DL 2) during or within 4 weeks after RT. The MTD was not reached; the probability of dose limiting toxicity at DL 4 was 0.15. All 18 evaluable patients underwent surgery, with low anterior resection in 7 (39%), proctectomy with coloanal anastomosis in 5 (28%), and abdominoperineal resection in 6 (33%) patients. Eight patients (44%) had pCR, and an additional 8 (44%) had ≤ 10% viable tumor in the surgical specimen. Fifteen patients (83%) had T downstaging. Three patients developed grade 3 post-operative complications (ileus, small bowel obstruction and infection). After a median follow-up of 21 months (range 9-39 months), no patient had local recurrence, but 1 patient developed distant metastasis. Conclusions: The combination of preoperative RT with concurrent capecitabine, bevacizumab and erlotinib was well tolerated. The pCR rate of 44% is promising and warrants further investigation. [Table: see text]

5016 Background: Everolimus is an oral rapamycin analog that selectively inhibits mTOR. PTEN mutations occur in 40-60% of endometrial cancer (EC). Although PTEN loss leads to constitutive activation of AKT and up-regulation of mTOR, it is not clear which EC patients will benefit from this targeted therapy. PS6K is a downstream marker of mTOR activation. Prior studies suggest KRAS mutations are associated with resistance to everolimus. We evaluated primary tumor specimens to determine if expression of biomarkers in the mTOR pathway or KRAS mutations would predict response to therapy. Methods: Correlative studies evaluating PTEN and PS6K expression by immunohistochemistry (IHC) and KRAS mutational analysis were performed from tissue blocks of primary tumor. Response to therapy was estimated with Fisher’s exact test. Positive predictive value (PPV) for each variable was calculated. Tumor from patients enrolled in a single institution, open-labeled, single arm, Phase II study in pretreated patients with recur...

246 Background: The role of cisplatin-based chemotherapy for the treatment of locally advanced or metastatic UC is well established. Pts with impaired renal function cannot receive cisplatin, however, and substitution with carboplatin yielded inferior results. We initiated a phase II study to assess the efficacy of gemcitabine, paclitaxel, and doxorubicin (GTA) treatment for UC in pts with renal insufficiency. Methods: Eligible pts had metastatic or unresectable UC of bladder, urethra, or upper tract, no prior chemotherapy, glomerular filtration rate < 60 ml/min, ECOG performance status ≤ 2, left ventricular ejection fraction > 40%, and adequate hematopoietic and hepatic function. Pts were excluded if they had brain metastasis, peripheral neuropathy ≥ grade 2, significant heart disease within 6 months of enrollment, or required hemodialysis. Outpatient treatment consisted of 900 mg/m2 gemcitabine, 135 mg/m2 paclitaxel, and 40 mg/m2 doxorubicin on day 1 every 2 weeks. Pegfilgrastim 6 mg sc was given immediately after GTA on day 1, or on day 2 if requested by the pt. Tumor evaluation was repeated every 3 cycles (6 weeks); treatment duration was limited to 9 cycles. A Simon 2-stage design was chosen to detect a target overall response rate of 40% and to reject a response rate of 25% or less. Results: Twenty-five pts enrolled and 21 could be assessed for response. Median (range) age was 72.8 years (53.4, 89.3) and 8 pts (32.0%) were female. RECIST responses occurred in 12 pts (4 complete; 8 partial), for an overall response rate of 57.1% (95% CI 34.0-78.2). Notable grade 3 and 4 toxicities were anemia (9 pts), thrombocytopenia (3 pts), neutropenia (2 pts), dyspnea (1 pt), mucositis (1 pt), and sepsis (1 pt). No adverse events were attributed to same-day pegfilgrastim and there were no treatment-related deaths. Eleven pts (44.0%) died of progressive disease; the median (range) follow-up time for 14 surviving pts was 5.5 months (2.3, 17.5). Conclusions: GTA has been well-tolerated in the setting of renal insufficiency, with an observed response rate in advanced UC exceeding the targeted response. The study will continue to a maximum of 72 pts. [Table: see text]

10060 Background: Sarcoma metastasizing to the heart is a difficult and complicated clinical problem, yet local control is feasible and effective for select patients with cardiac metastasis. Diligence is required to detect these lesions while still amenable to treatment, and echocardiogram remains the best tool for detecting cardiac disease. Methods: We reviewed all echocardiograms (1330) performed on 307 pediatric sarcoma patients treated at UT M. D. Anderson Cancer Center between 1997 and 2008. Measures of cardiac function and pathology (including size of ventricles and atria, function of ventricles and valves, presence of metastasis, and presence of pericardial effusion) were assigned numerical values. Fisher's exact test and the Wilcoxon rank-sum test compared clinical characteristics of patients with and without cardiac metastases. Results: The prevalence of cardiac metastases was 1.6% (5/307) with 95% confidence interval 0.5% to 3.8%. The presence of cardiac metastasis positively correlated with pericardial effusion (p = 0.001) and tricuspid valve insufficiency (p = 0.014). The probability of a patient with pericardial effusion having a cardiac metastasis was 28.6% (95% CI: 3.7%-71%). Of the 5 patients with documented sarcoma metastasis to the heart, 3 had widespread refractory disease, were given no cardiac-specific therapy, and rapidly died from disease. One patient who had widespread disease controlled with chemotherapy and radiation had open resection of 2 cardiac metastases which resulted in site-specific disease control for 6 months before succumbing to progressive extra-cardiac disease. Another patient had isolated cardiac metastasis, treated with open resection of 2 metastases followed by adjuvant chemotherapy, and has been without recurrent cardiac metastases for 5 years and 9 months. Conclusions: Durable local control for sarcoma metastasizing to the heart is possible and effective for select patients. Pericardial effusion merits evaluation for potential associated cardiac metastasis. Echocardiogram monitoring of sarcoma patients remains important, and should include screening for possible cardiac metastasis. No significant financial relationships to disclose.

20756 Background: Predicting inpatient mortality has clinical and financial implications and helps improve the care of advanced cancer patients and their families. Models are available for mortalit...

5502 Background: The finding of PTEN mutations in 40–60% of EC suggests this pathway is important in the pathogenesis of this disease. Loss of PTEN leads to constitutive activation of AKT, which le...

6079 Background: Young adults and older adolescents diagnosed to have cancer have had less progress in survival improvement than either younger or older patients (Proc. ASCO 21:389a, 2002). Because...

5065 Background: There is a perception that pts receiving high-dose chemotherapy with autologous stem cell support (HDCT) experience long-term detriments to overall QOL. To assess if changes in QOL...

9041 Background: Rhabdomyosarcoma (RMS) is an aggressive soft-tissue sarcoma, the most common in children, but rare in adults. Understanding the expression of molecules involved in apoptosis in RMS...

9531 Background: Women with Lynch Syndrome/HNPCC have a 40–60% lifetime risk of developing endometrial cancer (EC) and a 10–15% lifetime risk of developing ovarian cancer (OC). Expert panels have b...

8222 Background: We previously reported PREFs of chemo-experienced pts with ovarian cancer (ovca) enrolled on phase II trials of high-dose chemo/stem cell support (HDCT). To determine whether PREFs of previously treated pts differ from chemo-naive pts, we assessed longitudinal PREFs of newly diagnosed ovca pts scheduled to begin conventional-dose chemo (CDCT). Methods: Ovca pts receiving CDCT or HDCT were enrolled in this study. CDCT pts were newly diagnosed and dispositioned to receive 6 cycles of carboplatin/paclitaxel. HDCT pts received a mobilization regimen (MOB) of ifosfamide/etoposide and high-dose topotecan/melphalan/cyclophosphamide (TMC). Pts were interviewed at 2 points in time (T1, T2). For CDCT pts, T1 and T2 occurred at the 1st and 6th cycle of chemo. For HDCT pts, T1 occurred during MOB, T2 was after TMC. PREFs were assessed using a visual analog scale (VAS) and time trade-off (TTO) for the following SEs: alopecia, neuropathy, nausea/vomiting (NV), ototoxicity, fatigue, mucositis, dysuria, ...