Search

We report a measurement of the cross section for the process γγ→π+π- at invariant masses 500 MeV/c2 < mππ

Copious production of S* decaying into π+π- is observed in ψ decay. (974 ± 4 -i14 ± 5) MeV, consistent with the parameters extracted from couplede channel; fits to pheripheral π+π- and K+K- production experiments. The inclusive branching ratio for ψ → S* + X is found to be (0.42 ± 0.08)%. © 1981.

We present a high statistics measurement of the branching ratio for the decay τ-→π-μτ using data obtained with the Mark II detector at the SLAC e+e- storage ring SPEAR. We have used events from the center-of-mass energy region 3.52 to 6.7 GeV to determine that B(τ-→π-μτ)=0.117±0.004±0.018. From electron-muon events in the same data sample, we have determined that B(τ-→π-μτ) B(τ-→e--μeμτ)=0.66±0.03±0.11. We present measurements of the mass and spin of the τ and the mass of the τ neutrino based, for the first time, on a hadronic decay mode of the τ. © 1982.

A peak in the pK-+ and p»K+- invariant-mass spectra at 2.2850.006 GeV/c2 is observed, which is associated with the lowest-lying charmed baryon (c). A cross section times branching ratio of 0.0370.012 nb at Ec.m.=5.2 GeV is measured with a substantial fraction of the events produced with an equal recoiling mass. New measurements of inclusive p and cross sections are also presented, allowing an estimate of the branching ratio B(c+pK-+)=0.0220.010. © 1980 The American Physical Society.

Measurements are presented of the inclusive charged-particle cross sections s dσdx for e+e- annihilation at center-of-mass energies of 5.2, 6.5, and 29.0 GeV. Significant scale breaking is observed in these cross sections. © 1982 The American Physical Society.

Events of the type e+e-e+e-(958) have been observed with the Mark II detector at SPEAR by detecting the decay mode 0. From the observed cross section and known branching fractions of the is =5.91.61.2 keV and the total width is =3009060 keV (statistical and systematic errors). © 1979 The American Physical Society.

This Letter presents a measurement of the decay τ-→ρ-ντ using data obtained with the Mark II detector at SPEAR. In the center-of-mass energy region 4.5

A high-statistics study of decays into baryon final states has been done with the Mark II detector at SPEAR. A detailed test of baryon-antibaryon decay modes is presented. Substantial resonance formation is observed in multibody decays of the involving baryons. Branching ratios for a large number of decay modes are given, including the radiative decay pp. The flavor-SU(3)-forbidden decays (1385)+charge conjugate are observed with substantial branching ratios. © 1984 The American Physical Society.

The prompt photon decay (3095)+-+- has been studied with the Mark II detector at SPEAR. This channel is found to contain a 00 component with 00 masses concentrated between 1.4 and 2.0 GeV/c2. The branching fraction for the 00 decay with masses less than 2.0 GeV/c2 is measured to be (1.25±0.35±0.40)×10-3. © 1982 The American Physical Society.

In a study of (3684) radiative decays with the Mark II detector at SPEAR, the decay sequence c (2980) is observed, with the c (2980) decaying into several completely reconstructed hadronic modes. A mass M=29808 MeV/c2 and a width

The inclusive and 0 momentum distributions at the have been measured. Using these data and estimates of production, it is found that (4.1 0.8)% of decays contain a direct photon with energy greater than 60% of the beam energy. The expected momentum distribution for direct photons calculated to lowest order in quantum chromodynamics is qualitatively different from that observed in the data. © 1980 The American Physical Society.

This Letter presents a measurement of the branching fraction for the Cabibbo-suppressed decay -K*-(892) with use of data obtained with the Mark-II detector at SPEAR. Eleven events containing a K*(892) in coincidence with a muon or an electron of opposite charge were found in data which span the center-of-mass energy region 4.2

Direct electrons are observed in baryon events produced in e+e- annihilation at center-of-mass energies above the c»c threshold. These events are attributed to charmed-baryon pair production and subsequent c semileptonic decay. Various semileptonic branching ratios of the c are determined, including B(ce+X)=(4.5 1.7)%. © 1982 The American Physical Society.

The decay mode ψ′→γγψ has been studied with the Mark-II detector at SPEAR. New measurements of branching ratios for decays of the type ψ′→γχ, χ→γψ involving known χ states are presented. The existence of a χ state of mass near 3455 MeV/c2 produced in this decay chain is not confirmed, and the upper limit (90% confidence level) of the product of branching ratios is measured to be 0.13%. A new decay mode, ψ′→π0ψ, which violates isospin conservation is observed with branching ratio (0.15±0.06)%. © 1980 The American Physical Society.

The D Cabibbo-suppressed decay modes -+ and K-K+ have been observed and the following ratios of D partial decay widths have been measured: (D-+)(DK-+)=0.0330.015 and (DK-K+)(DK-+)=0.1130.030. © 1979 The American Physical Society.

Measurements of ψ(3097) and ψ′(3686) branching fractions for selected hadronic decays are presented. The ratio of ψ′ to ψ branching fractions for these decays is consistent with the ratio of branching fractions to lepton pairs, with the exception of the decays to pπ and K*K for which this ratio is substantially smaller. © 1983 The American Physical Society.

We present results of a detailed analysis of inclusive direct photon production at the (3095). The direct-photon momentum distribution for x>0.4 is presented and compared with the leading-order quantum-chromodynamic prediction. The total production rate is found to be consistent with theoretical expectations, but the observed momentum distribution is considerably softer. Results of an analysis of some inclusive properties of the hadronic system recoiling against the direct photon are presented. The mean charged-particle and Ks multiplicities are presented as functions of the invariant mass of the hadronic system. These data agree well with the corresponding mean multiplicities measured in e+e- annihilations at center-of-mass energies comparable to the invariant mass of the hadronic system. © 1981 The American Physical Society.

We present a measurement of the cross section for hadron production by e+e- annihilation in the vicinity of the previously observed resonance near 3.77 GeV. The data are used to determine the parameters of the (3770) resonance. The values found are: mass, 3764±5 MeV/c2, total width, 23.5±5 MeV, and partial width to electron pairs, 276±50 eV. © 1980 The American Physical Society.

The Mark II detector at SPEAR has been used to study D-meson production in e+e- annihilation at center-of-mass energies between 3.8 and 6.7 GeV. The neutral and charged D mesons are identified from their K and K decay modes. Measurements of RD and of the inclusive differential cross section s ddz are presented. The quasi-two-body cross sections DD, D*D, and D*D* are derived from an overall fit to the D recoil spectra. No evidence was found for the associated production of charmed mesons and charmed baryons. © 1982 The American Physical Society.

The branching fraction for the Cabibbo-suppressed decay τ-→K-ντ is measured from data obtained with the Mark II detector at SPEAR. Fifteen events containing a K± in coincidence with a muon or electron of opposite charge are observed. It is determined that B(τ-→K-ντ)=(1.3±0.5)%. © 1982 The American Physical Society.

Searches for 12 neutrinoless decay modes of the which violate lepton-number conservation have been made using the reaction e+e-+-. No evidence for lepton-number violation is observed, and we have set upper limits (90% C.L.) on the branching ratio for each decay mode. The branching-ratio limits on the radiative decays and e are 0.055 and 0.064%, respectively. For the charged lepton decays ee, eee, and, the branching ratio limits are 0.040, 0.033, 0.044, and 0.049%, respectively. Upper limits on the branching ratios for the following charged lepton + neutral hadron decays are 0 (0.037%), 0 (0.044%), eK0 (0.13%), K0 (0.10%), 0 (0.21%), and 0 (0.082%). We also use these data to search for the pair production in e+e- annihilation of some unconventional particles with masses less than about 3 GeV/c2. © 1982 The American Physical Society.

We present a measurement of the cross section for the reaction e+e- → e+e-π+π-π+π-at SPEAR. This channel is found to be large and dominated by the process γγ → ρ{variant}0ρ{variant}0 → π+π-π+π-. The cross section, which is small just above the four-pion threshold, exhibits a large enhancement near the ρ{variant}0ρ{variant}0 threshold. © 1981.

A high-statistics study of decays into baryon final states has been done with the Mark II detector at SPEAR. A detailed test of baryon-antibaryon decay modes is presented. Substantial resonance formation is observed in multibody decays of the involving baryons. Branching ratios for a large number of decay modes are given, including the radiative decay pp. The flavor-SU(3)-forbidden decays (1385)+charge conjugate are observed with substantial branching ratios. © 1984 The American Physical Society.

We present a measurement of the cross section for hadron production by e+e- annihilation in the vicinity of the previously observed resonance near 3.77 GeV. The data are used to determine the parameters of the (3770) resonance. The values found are: mass, 3764±5 MeV/c2, total width, 23.5±5 MeV, and partial width to electron pairs, 276±50 eV. © 1980 The American Physical Society.

Events of the type e+e-e+e-(958) have been observed with the Mark II detector at SPEAR by detecting the decay mode 0. From the observed cross section and known branching fractions of the is =5.91.61.2 keV and the total width is =3009060 keV (statistical and systematic errors). © 1979 The American Physical Society.

Searches for 12 neutrinoless decay modes of the which violate lepton-number conservation have been made using the reaction e+e-+-. No evidence for lepton-number violation is observed, and we have set upper limits (90% C.L.) on the branching ratio for each decay mode. The branching-ratio limits on the radiative decays and e are 0.055 and 0.064%, respectively. For the charged lepton decays ee, eee, and, the branching ratio limits are 0.040, 0.033, 0.044, and 0.049%, respectively. Upper limits on the branching ratios for the following charged lepton + neutral hadron decays are 0 (0.037%), 0 (0.044%), eK0 (0.13%), K0 (0.10%), 0 (0.21%), and 0 (0.082%). We also use these data to search for the pair production in e+e- annihilation of some unconventional particles with masses less than about 3 GeV/c2. © 1982 The American Physical Society.

The prompt photon decay (3095)+-+- has been studied with the Mark II detector at SPEAR. This channel is found to contain a 00 component with 00 masses concentrated between 1.4 and 2.0 GeV/c2. The branching fraction for the 00 decay with masses less than 2.0 GeV/c2 is measured to be (1.25±0.35±0.40)×10-3. © 1982 The American Physical Society.

In a study of (3684) radiative decays with the Mark II detector at SPEAR, the decay sequence c (2980) is observed, with the c (2980) decaying into several completely reconstructed hadronic modes. A mass M=29808 MeV/c2 and a width

The inclusive and 0 momentum distributions at the have been measured. Using these data and estimates of production, it is found that (4.1 0.8)% of decays contain a direct photon with energy greater than 60% of the beam energy. The expected momentum distribution for direct photons calculated to lowest order in quantum chromodynamics is qualitatively different from that observed in the data. © 1980 The American Physical Society.

This Letter presents a measurement of the branching fraction for the Cabibbo-suppressed decay -K*-(892) with use of data obtained with the Mark-II detector at SPEAR. Eleven events containing a K*(892) in coincidence with a muon or an electron of opposite charge were found in data which span the center-of-mass energy region 4.2

The D Cabibbo-suppressed decay modes -+ and K-K+ have been observed and the following ratios of D partial decay widths have been measured: (D-+)(DK-+)=0.0330.015 and (DK-K+)(DK-+)=0.1130.030. © 1979 The American Physical Society.

Copious production of S* decaying into π+π- is observed in ψ decay. (974 ± 4 -i14 ± 5) MeV, consistent with the parameters extracted from couplede channel; fits to pheripheral π+π- and K+K- production experiments. The inclusive branching ratio for ψ → S* + X is found to be (0.42 ± 0.08)%. © 1981.

We have observed a radiative transition from the ψ to a state decaying into KSK±π∓, with mass M = 1.44-0.015+0.01 GeV/c2 and width Γ = 0.05-0.02+0.03 GeV/c2. We tentatively identify this state as the E(1420). Assuming that this state is an isospin singlet, we have determined the branching fraction product B(ψ → γE) × B(E × KKπ) = (3.6 ± 1.4) × 10-3. © 1980.

Background: Neoadjuvant chemotherapy improves the survival of patients with high-risk urothelial cancer. However, the lack of curative alternatives to cisplatin-based chemotherapy is limiting for patients with neuropathy or hearing loss. Sequential chemotherapy also has not been well studied in the neoadjuvant setting. The authors explored sequential neoadjuvant ifosfamide-based chemotherapy in a patient cohort at high risk of noncurative cystectomy.Methods: Patients with muscle-invasive cancer and lymphovascular invasion, hydronephrosis, clinical T3b and T4a (cT3b-4a) disease (defined as a 3-dimensional mass on examination under anesthetic or invasion into local organs), micropapillary tumors, or upper tract disease received 3 cycles of combined ifosfamide, doxorubicin, and gemcitabine followed by 4 cycles of combined cisplatin, gemcitabine, and ifosfamide. The primary endpoint was downstaging to pT1N0M0 disease or lower.Results: At a median follow-up of 85.3 months, the 5-year overall survival (OS) and disease-specific survival (DSS) rates for all 65 patients were 63% and 68%, respectively (95% confidence interval: 5-year OS rate, 0.52%-0.76%; 5-year DSS rate, 0.58%-0.81%). Pathologic downstaging to pT1N0 disease or lower occurred in 50% of patients who underwent cystectomy and in 60% of patients who underwent nephroureterectomy and was correlated with the 5-year OS rate (pT1N0 disease or lower, 87%; pT2-pT3aN0 disease, 67%; and pT3b disease or higher or lymph node-negative disease, 27%; P ≤ .001 for pT1 or lower vs pT2 or higher). Variant histology was associated with an inferior 5-year DSS rate (50% vs 83% in pure transitional cell carcinoma; P = .02). The most frequent grade 3 toxicities were infection (38%), febrile neutropenia (22%), and mucositis (18%). There were 3 grade 4 toxicities (myocardial infarction, thrombocytopenia, and vomiting) and 1 grade 5 toxicity in a patient who refused antibiotics for pneumonia.Conclusions: Sequential therapy was active and maintained the historic expectation of achieving a cure. The current results strongly reinforced previous experience suggesting that pathologic downstaging to pT1N0 disease or less is a useful surrogate for eventual cure in patients with urothelial cancer. [ABSTRACT FROM AUTHOR]

We assessed the activity and safety of a biochemotherapy regimen in which courses of paclitaxel, methotrexate, and cisplatin were alternated with courses of 5-fluorouracil, alpha-interferon, and cisplatin in the treatment of refractory urothelial carcinoma. Forty patients were enrolled in the study. In the phase I portion, 15 patients were treated according to an escalating dosage regimen designed to determine the maximum tolerated dose. A total of 30 patients received treatment according to the maximum tolerated dose regimen: methotrexate (30 mg/m(2)) given iv on days 1 and 22; paclitaxel (175 mg/m(2)) given iv over 3 h on day 1; cisplatin (70 and 25 mg/m(2)) administered iv on days 1 and 22, respectively; 5-fluorouracil (400 mg/m(2)) given iv by continuous infusion daily for 5 days beginning on day 22; and alpha-interferon (4 mIU/m(2)) given SC daily for 5 days simultaneously with the 5-fluorouracil infusions. The regimen was repeated at 42-day intervals. The 40 treated patients had an overall response rate of 43%, a complete response rate of 18%, and a median survival time of 44 weeks. Most of the toxic effects were hematologic: Grade 4 neutropenia occurred in 30% of patients (12 patients) and Grade 3 thrombocytopenia in 20% (8 patients). Even though this alternating biochemotherapy regimen was active for patients with refractory urothelial carcinoma, its activity was not better than that of certain single cytotoxic agents. Furthermore, the complicated dosing schedule and toxic effects of the regimen precluded its routine use in the treatment of urothelial carcinoma. [ABSTRACT FROM AUTHOR]

Patients with refractory advanced or metastatic urothelial carcinoma derive only minor benefit from chemotherapy. Based on evidence that urothelial carcinoma may be associated with impaired immunological reactivity, we conducted a phase II trial of interleukin-2 (IL-2), a biologic response modifier, to assess its efficacy and toxicity in treating refractory advanced or metastatic urothelial carcinoma. Seventeen patients with urothelial carcinoma who had undergone no more than 1 cisplatin-containing chemotherapy regimen were treated with IL-2 at a dose of 3 × 106 IU/m2/day by continuous intravenous infusion for 4 consecutive days each week for 4 weeks. Cycles were to be repeated every 6 weeks until disease progression. Toxic effects could be assessed in all 17 patients and response in 13. The most common grade III and IV toxic effects included hypotension (13/17); anemia (6/17); thrombocytopenia (4/17); granulocytopenia (3/17); and, in 1 patient each, cardiac ischemia, bowel perforation, and an increase in creatinine level. One sudden death was assumed to be treatment related. Although we found no objective antitumor activity for IL-2, median patient survival was 10.5 months (95% confidence interval, 5.8 to 17.1 months), with a 15.9-month median survival for 3 patients with poor performance status and visceral metastases. Further clinical investigation of the biological effect of IL-2 in urothelial carcinoma may be warranted. [Copyright &y& Elsevier]

Background: We hypothesized that pretreatment serum levels of insulin and other serum markers would predict Progression-free survival (PFS), defined as time to castration-resistant progression or death, in metastatic androgen-dependent prostate cancer (mADPC)., Methods: Serum samples from treatment-naïve men participating in a randomized phase 3 trial of ADT +/- chemotherapy were retrospectively analyzed using multiplex assays for insulin and multiple other soluble factors. Cox proportional hazards regression models were used to identify associations between individual factor levels and PFS., Results: Sixty six patients were evaluable (median age = 72 years; median prostate surface antigen [PSA] = 31.5 ng/mL; Caucasian = 86 %; Gleason score ≥8 = 77 %). In the univariable analysis, higher insulin (HR = 0.81 [0.67, 0.98] p = 0.03) and C-peptide (HR = 0.62 [0.39, 1.00]; p = 0.05) levels were associated with a longer PFS, while higher Hepatocyte Growth Factor (HGF; HR = 1.63 [1.06, 2.51] p = 0.03) and Osteopontin (OPN; HR = 1.56 [1.13, 2.15]; p = 0.01) levels were associated with a shorter PFS. In multivariable analysis, insulin below 2.1 (ln scale; HR = 2.55 [1.24, 5.23]; p = 0.011) and HGF above 8.9 (ln scale; HR = 2.67 [1.08, 3.70]; p = 0.027) levels were associated with longer PFS, while adjusted by OPN, C-peptide, trial therapy and metastatic volume. Four distinct risk groups were identified by counting the number of risk factors (RF) including low insulin, high HGF, high OPN levels, and low C-peptide levels (0, 1, 2, and 3). Median PFS was 9.8, 2.0, 1.6, and 0.7 years for each, respectively (p < 0.001)., Conclusion: Pretreatment serum insulin, HGF, OPN, and C-peptide levels can predict PFS in men with mADPC treated with ADT. Risk groups based on these factors are superior predictors of PFS than each marker alone.

Gene therapy development has been limited by our inability to target multifocal cancer with systemic delivery. We developed a systemically administered, tumor-targeted liposomal nanodelivery complex (SGT-94) carrying a plasmid encoding RB94, a truncated form of the RB gene. In preclinical studies, RB94 showed marked cytotoxicity against tumor but not normal cells. SGT-94 was administered intravenously in a first-in-man study in metastatic genitourinary cancer. Minimal side effects were observed; dose-limiting toxicity (DLT) has not been reached in 11 evaluable patients. There was evidence of clinical activity at the 2.4 mg dose with one complete remission (CR) and one partial remission (PR). The patient in CR was retreated upon progression and had a second PR. Furthermore, there was tumor-specific targeting of the SGT-94 complex. One patient had wedge resections of two lung metastases which demonstrated RB94 expression at the DNA level by polymerase chain reaction (PCR) and at the protein level by Western blotting, with no RB94 present in normal contiguous lung. In conclusion, systemically delivered SGT-94 showed evidence of selective tumor targeting and was well tolerated with evidence of clinical activity. Additional studies are warranted to explore the activity of this drug as a single agent and in combination therapy.

Background: Gene expression profiling (GEP) suggests there are three subtypes of muscle-invasive urothelial cancer (UC): basal, which has the worst prognosis; p53-like; and luminal. We hypothesized that GEP of transurethral resection (TUR) and cystectomy specimens would predict subtypes that could benefit from chemotherapy., Objective: To explore clinical outcomes for patients treated with dose-dense (DD) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and bevacizumab (B) and the impact of UC subtype., Design, Setting, and Participants: Sixty patients enrolled in a neoadjuvant trial of four cycles of DDMVAC + B between 2007 and 2010. TUR and cystectomy specimens for GEP were available from 38 and 23 patients, respectively, and from an additional confirmation cohort of 49 patients treated with perioperative MVAC., Outcome Measurements and Statistical Analysis: Relationships with outcomes were analyzed using multivariable Cox regression and log-rank tests., Results and Limitations: Chemotherapy was active, with pT0N0 and ≤pT1N0 downstaging rates of 38% and 53%, respectively, and 5-yr overall survival (OS) of 63%. Bevacizumab had no appreciable impact on outcomes. Basal tumors had improved survival compared to luminal and p53-like tumors (5-yr OS 91%, 73%, and 36%, log-rank p=0.015), with similar findings on multivariate analysis. Bone metastases within 2 yr were exclusively associated with the p53-like subtype (p53-like 100%, luminal 0%, basal 0%; p ≤ 0.001). Tumors enriched with the p53-like subtype at cystectomy suggested chemoresistance for this subtype. A separate cohort treated with perioperative MVAC confirmed the UC subtype survival benefit (5-yr OS 77% for basal, 56% for luminal, and 56% for p53-like; p=0.021). Limitations include the small number of pretreatment specimens with sufficient tissue for GEP., Conclusion: GEP was predictive of clinical UC outcomes. The basal subtype was associated with better survival, and the p53-like subtype was associated with bone metastases and chemoresistant disease., Patient Summary: We can no longer think of urothelial cancer as a single disease. Gene expression profiling identifies subtypes of urothelial cancer that differ in their natural history and sensitivity to chemotherapy., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Receptors in tumor blood vessels are attractive targets for ligand-directed drug discovery and development. The authors have worked systematically to map human endothelial receptors ("vascular zip codes") within tumors through direct peptide library selection in cancer patients. Previously, they selected a ligand-binding motif to the interleukin-11 receptor alpha (IL-11Rα) in the human vasculature., Methods: The authors generated a ligand-directed, peptidomimetic drug (bone metastasis-targeting peptidomimetic-11 [BMTP-11]) for IL-11Rα-based human tumor vascular targeting. Preclinical studies (efficacy/toxicity) included evaluating BMTP-11 in prostate cancer xenograft models, drug localization, targeted apoptotic effects, pharmacokinetic/pharmacodynamic analyses, and dose-range determination, including formal (good laboratory practice) toxicity across rodent and nonhuman primate species. The initial BMTP-11 clinical development also is reported based on a single-institution, open-label, first-in-class, first-in-man trial (National Clinical Trials number NCT00872157) in patients with metastatic, castrate-resistant prostate cancer., Results: BMTP-11 was preclinically promising and, thus, was chosen for clinical development in patients. Limited numbers of patients who had castrate-resistant prostate cancer with osteoblastic bone metastases were enrolled into a phase 0 trial with biology-driven endpoints. The authors demonstrated biopsy-verified localization of BMTP-11 to tumors in the bone marrow and drug-induced apoptosis in all patients. Moreover, the maximum tolerated dose was identified on a weekly schedule (20-30 mg/m(2) ). Finally, a renal dose-limiting toxicity was determined, namely, dose-dependent, reversible nephrotoxicity with proteinuria and casts involving increased serum creatinine., Conclusions: These biologic endpoints establish BMTP-11 as a targeted drug candidate in metastatic, castrate-resistant prostate cancer. Within a larger discovery context, the current findings indicate that functional tumor vascular ligand-receptor targeting systems may be identified through direct combinatorial selection of peptide libraries in cancer patients., (© 2015 American Cancer Society.)

Background: Preclinical data suggest that anti-vascular endothelial growth factor agents combined with mammalian target of rapamycin inhibitors yield synergistic antitumor effects. A phase I trial with a 3+3 dose escalation design of S with T was stopped after the first dose pair led to 2 of 3 patients experiencing dose-limiting toxicity (DLT)., Patients and Methods: To explore multiple potential dosing pairs of S and T, a 2-stage outcome-adaptive Bayesian dose-finding method was designed. The primary objective was to find the MTD of S and T in patients with advanced renal cell carcinoma. A 3-week treatment cycle consisted of daily S, 2 weeks of treatment, 1 week without treatment, and weekly T., Results: Twenty patients received study drugs; the median number of previous therapies was 1. The number of patients (S and T doses in mg) was: 2 (S, 12.5; T, 6), 1 (S, 25; T, 12.5), 1 (S, 12.5; T, 8), 8 (S, 12.5 alternate 25; T, 9), 2 (S, 25; T, 6), 2 (S, 25 alternate 37.5; T, 6), 2 (S, 37.5; T, 6), and 2 (S, 37.5; T, 8). Six patients required dose reduction, 3 because of Grade 3 stomatitis, 2 because of Grade 3 thrombocytopenia; the mean number of cycles was 6.6 ± 5.3, the mean time during study was 159 ± 120 days. One patient experienced a DLT in cycle 1 and was nonevaluable, 1 had a partial response, 16 had stable disease, and 2 had progressive disease as best response. There were 21 Grade 3/4 adverse events but no treatment-related deaths., Conclusion: The MTD of S and T were not determined because of premature trial closure. S 37.5 mg/d, 2 weeks of treatment, 1 week with no treatment, and T 8 mg to 10 mg weekly are close to the MTD., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To characterise the incidence, onset, management, predictors, and clinical impact of mammalian target of rapamycin (mTOR) inhibitor-associated non-infectious pneumonitis (NIP) on patients with metastatic renal cell carcinoma (mRCC)., Patients and Methods: Retrospective review of 310 patients with mRCC who received temsirolimus and/or everolimus between June 2007 and October 2010. Clinical correlations were made with serial radiological imaging. Fisher's exact, Wilcoxon rank-sum, and logistic regression analyses were used to evaluate the association of NIP with demographic or clinical factors. Log-rank and Cox proportional hazards regression analyses were used for the time-to-event analysis., Results: NIP occurred in 6% of temsirolimus-treated and 23% of everolimus-treated patients. Symptoms included cough, dyspnoea, and fever (median of two and three symptoms per patient, respectively). The median National Cancer Institute Common Toxicity Criteria for Adverse Events pneumonitis grade was 2 for both groups. Older age and everolimus treatment were predictive of NIP. Patients who developed NIP had a significantly longer time on treatment (median 4.1 vs 2 months) and overall survival (OS) (median 15.4 vs 7.4 months). NIP was a predictor of improved OS by multivariate analysis., Conclusions: There was an increased incidence of NIP in everolimus-treated patients. Improved OS in patients who developed NIP is an intriguing finding and should be further investigated. Given the incidence, morbidity, and outcomes seen in patients on everolimus who develop NIP, management should include proactive monitoring and treatment of NIP with the goal of preserving mTOR inhibitor therapy., (© 2013 The Authors. BJU International © 2013 BJU International.)

Purpose: We evaluated the survival of patients with muscle invasive bladder cancer undergoing radical cystectomy without neoadjuvant chemotherapy to confirm the utility of existing clinical tools to identify low risk patients who could be treated with radical cystectomy alone and a high risk group most likely to benefit from neoadjuvant chemotherapy., Materials and Methods: We identified patients with muscle invasive bladder cancer who underwent radical cystectomy without neoadjuvant chemotherapy at our institution between 2000 and 2010. Patients were considered high risk based on the clinical presence of hydroureteronephrosis, cT3b-T4a disease, and/or histological evidence of lymphovascular invasion, micropapillary or neuroendocrine features on transurethral resection. We evaluated survival (disease specific, progression-free and overall) and rate of pathological up staging. An independent cohort of patients from another institution was used to confirm our findings., Results: We identified 98 high risk and 199 low risk patients eligible for analysis. High risk patients exhibited decreased 5-year overall survival (47.0% vs 64.8%) and decreased disease specific (64.3% vs 83.5%) and progression-free (62.0% vs 84.1%) survival probabilities compared to low risk patients (p <0.001). Survival outcomes were confirmed in the validation subset. On final pathology 49.2% of low risk patients had disease up staged., Conclusions: The 5-year disease specific survival of low risk patients was greater than 80%, supporting the distinction of high risk and low risk muscle invasive bladder cancer. The presence of high risk features identifies patients with a poor prognosis who are most likely to benefit from neoadjuvant chemotherapy, while many of those with low risk disease can undergo surgery up front with good expectations and avoid chemotherapy associated toxicity., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)