Treatment-specific risk of subsequent malignant neoplasms in five-year survivors of diffuse large B-cell lymphoma.

BACKGROUND: The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors. METHODS: Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression. RESULTS: After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin versus ≤2250 mg/m2/≤150 mg/m2, respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab. CONCLUSION: Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up for rituximab-treated patients.

Bilateral breast cancer, synchronous and metachronous; differences and outcome.

The aims of this study were twofold: to analyze the incidence of patients having synchronous or metachronous bilateral invasive breast cancer (SBBC and MBBC) and to assess the characteristics and outcome compared to those having unilateral breast cancer (UBC). The used data were obtained from our prospective population-based cohort study which had been started in 1983. Bilateral breast cancer (BBC) was categorized as SBBC (≤3 months of the first primary) or MBBC (>3 months after the first primary). The incidence of SBBC was 1% and that of MBBC 7.0 %. Patients with UBC showed more ductal carcinoma compared to patients with BBC. MBBC status was an independent significant predictor of local failure (HR 1.9; 95% CI 1.3-2.7). SBBC status was an independent predictor of distant metastases (HR 2.6; 95% CI 1.4-4.5). Overall survival (OS) was better for MBBC (HR 0.6; 95% CI 0.4-0.8) and worse for SBBC (HR 2.3; 95% CI 1.5-3.6) compared to UBC. We noted: (1) MBBC showed a significant higher local failure compared to UBC, (2) SBBC, compared to MBBC and UBC had a significant higher distant metastases rate, (3) disease-specific survival and OS were significantly worse for SBBC compared to UBC and MBBC, and (4) that the OS for MBBC compared to UBC, was significantly better.

Survey response of oral and maxillofacial surgeons on invasive procedures in patients using antithrombotic medication.

The aim was to evaluate the management strategies of Dutch oral and maxillofacial surgeons when performing invasive dental or oral surgery in patients using oral antithrombotic medication (OAM). In November 2009 a survey was mailed to all 213 members of the Dutch Society for Oral and Maxillofacial Surgery. A response rate of 57% was achieved with 79 surveys returned through mail and 38 surveys answered through the Internet. The results show that many different treatment strategies are advocated by Dutch oral and maxillofacial surgeons, regarding preferred international normalised ratio (INR) value and continuation or discontinuation of OAM prior to invasive dental or oral surgery. The risk of bleeding during or after an invasive dental procedure was overestimated. A need for a practice guideline on this topic was expressed by 73% of respondents.

The M694V mutation in Armenian-Americans: a 10-year retrospective study of MEFV mutation testing for familial Mediterranean fever at UCLA.

Familial Mediterranean fever (FMF), inherited in an autosomal recessive manner, is a systemic auto-inflammatory disorder characterized by recurrent attacks of fever with peritonitis, pleuritis, synovitis and erysipeloid rash. The marenostrin-encoding fever (MEFV) gene, located on chromosome 16p13.3, is the only gene in which mutations are currently known to cause FMF. To correlate specific genotypes with adverse phenotypes of affected populations residing in the Western United States, a retrospective case series review was conducted of all MEFV gene mutation testing completed at UCLA Clinical Molecular Diagnostic Laboratory between February 2002 and February 2012, followed by clinical chart review of all subjects who either have a single or double mutation. All 12 common mutations in the MEFV gene were analyzed and the M694V variant was found to be associated with an adverse FMF clinical outcome in the Armenian-American population, manifested by earlier onset of disease, increased severity of disease, and renal amyloidosis.

Quantum heating of a nonlinear resonator probed by a superconducting qubit.

We measure the quantum fluctuations of a pumped nonlinear resonator using a superconducting artificial atom as an in situ probe. The qubit excitation spectrum gives access to the frequency and amount of excitation of the intracavity field fluctuations, from which we infer its effective temperature. These quantities are found to be in agreement with theoretical predictions; in particular, we experimentally observe the phenomenon of quantum heating.

Ultrasensitive magnetic field detection using a single artificial atom.

Efficient detection of magnetic fields is central to many areas of research and technology. High-sensitivity detectors are commonly built using direct-current superconducting quantum interference devices or atomic systems. Here we use a single artificial atom to implement an ultrasensitive magnetometer with micron range size. The artificial atom, a superconducting two-level system, is operated similarly to atom and diamond nitrogen-vacancy centre-based magnetometers. The high sensitivity results from quantum coherence combined with strong coupling to magnetic field. We obtain a sensitivity of 3.3 pT Hz(-1/2) for a frequency at 10 MHz. We discuss feasible improvements to increase sensitivity by one order of magnitude. The intrinsic sensitivity of this detector at frequencies in the 100 kHz-10 MHz range compares favourably with direct-current superconducting quantum interference devices and atomic magnetometers of equivalent spatial resolution. This result illustrates the potential of artificial quantum systems for sensitive detection and related applications.

Characterization of a two-transmon processor with individual single-shot qubit readout.

We report the characterization of a two-qubit processor implemented with two capacitively coupled tunable superconducting qubits of the transmon type, each qubit having its own nondestructive single-shot readout. The fixed capacitive coupling yields the sqrt[iSWAP] two-qubit gate for a suitable interaction time. We reconstruct by state tomography the coherent dynamics of the two-bit register as a function of the interaction time, observe a violation of the Bell inequality by 22 standard deviations after correcting readout errors, and measure by quantum process tomography a gate fidelity of 90%.

Circuit QED with a nonlinear resonator: ac-Stark shift and dephasing.

We have performed spectroscopic measurements of a superconducting qubit dispersively coupled to a nonlinear resonator driven by a pump microwave field. Measurements of the qubit frequency shift provide a sensitive probe of the intracavity field, yielding a precise characterization of the resonator nonlinearity. The qubit linewidth has a complex dependence on the pump frequency and amplitude, which is correlated with the gain of the nonlinear resonator operated as a small-signal amplifier. The corresponding dephasing rate is found to be close to the quantum limit in the low-gain limit of the amplifier.

Strong coupling of a spin ensemble to a superconducting resonator.

We report the realization of a quantum circuit in which an ensemble of electronic spins is coupled to a frequency tunable superconducting resonator. The spins are nitrogen-vacancy centers in a diamond crystal. The achievement of strong coupling is manifested by the appearance of a vacuum Rabi splitting in the transmission spectrum of the resonator when its frequency is tuned through the nitrogen-vacancy center electron spin resonance.

The impact of margin status in breast-conserving therapy for lobular carcinoma is age related.

PURPOSE: The aim is to look at the impact of margin status and outcome of invasive lobular carcinoma (ILC) treated with breast-conserving therapy (BCT). METHODS: This manuscript describes an analysis on 330 BCT in 318 patients with ILC. RESULTS: The 12-year local relapse free survival (LRFS) is 89%. In multivariate analysis, positive margin status, age>50 years, contra lateral breast cancer, and adjuvant systemic therapy were significant predictors of local relapse free survival. In a separate analysis limited to a positive margin for invasive carcinoma or carcinoma in situ, only a positive margin for invasive carcinoma was a significant predictor of local relapse free survival. This was limited to women

GnRH agonist and GnRH antagonist in intracytoplasmic injection cycles.

The long agonistic protocol for controlled ovarian hyperstimulation (COH) is effective and used most often, thus is considered the gold standard. Therefore any new regimen has to be compared in its results with those obtained with the long protocol. This report compares the efficacy of GnRH agonist and antagonist in a retrospective study of IVF/ICSI carried out in a tertiary teaching hospital from 2003 to 2006. Only the first COH cycle followed by IVF-ICSI from 200 couples (agonist = 120 and antagonist = 80) were analysed. The end points studied included the number of oocytes recovered, number of mature (MII) oocytes, fertilization, cleavage, morphology based embryo quality, pregnancy rate, quantity and cost of gonadotrophin. The average age of female subjects was 35.1 +/- 4.7 years with 50% being 35 years and above. Major infertility factors were tubal blockage, male factor and endometriosis altogether comprising 68%. GnRH agonist and antagonist cycle parameters were comparable except lesser amount of gonadotrophin was used with lower resultant costs (both p < 0.0005) in antagonistic regime. Antagonist regime produce somewhat more good quality embryos (p = 0.065), an insignificant difference. A clinical pregnancy rate per embryo transfer of 16.3% in agonist and 20.6% in antagonist regime was achieved respectively. In conclusion, GnRH antagonist protocol produced a COH response, embryonic development and pregnancy rates on par to GnRH agonist regime. Moreover GnRH antagonist protocol required a shorter stimulation period plus fewer complications. Hence GnRH antagonist regime provided means for a friendlier, convenient and cost effective protocol for patients.

Affordable ART for developing countries: a cost benefit comparison of low dose stimulation versus high dose GnRH antagonist protocol.

OBJECTIVE: Low dose stimulation (LS) is emerging as an alternative regime in assisted reproductive technology (ART). This study aimed to compare the cost-effectiveness of LS to the high dose GnRH antagonist (Atg) regime. METHODS: An observational prospective study conducted at an academic infertility unit from January to June 2007. Outcome measures included the numbers of follicles, oocytes and embryos, morphological quality of oocytes and embryos, clinical pregnancy (PR) and complication rate. RESULT: Ninety five first attempt ICSI cycles consisting of 54 LS and 41 Atg were analyzed. Subjects in both groups had comparable sociodemographics and reproductive characteristics. LS generated significantly fewer follicles, total oocytes, mature oocytes (all p < 0.0005) and immature oocytes (p = 0.009) than Atg but the number of excellent quality oocytes was similar. Significantly fewer embryos were available in LS although the proportion of usable embryos was higher, 83.2% vs. 67.0% for Atg. Mean embryos per transfer was 2.0 +/- 1.1 vs. 2.6 +/- 1.0 (p = 0.02) for a clinical PR per transfer of 43.2% vs. 50.0% for LS and Atg respectively. LS regime had a shorter gonadotrophin administration period with resultant COH cost one third of the Atg protocol (both, p < 0.0005). The cost per live birth per started cycle worked out to be USD 13,200 and 24,900 for LS and Atg respectively. Furthermore, LS had fewer incidences of OHSS compared to the Atg regime, 3.7% vs. 12.2%. CONCLUSION: LS cost benefits included lower amounts of gonadotrophin used and fewer injections. It is a viable alternative regime in producing comparable clinical PR at lower cost and less complication in ART.

Emergency department thoracotomy for pericardiac tamponade.

A 31-year-old man with a penetrating chest injury presented acutely with pulseless electrical activity, as a result of a ventricular laceration causing pericardial tamponade. Emergency department thoracotomy was performed to release the tamponade and he was operated on immediately to repair the laceration. He subsequently survived and was discharged to a community hospital for rehabilitation. We present this case of penetrating cardiac injury in which the patient arrived in extremis and for which emergency department thoracotomy was performed, and we discuss the role of emergency thoracotomy, its indications and outcome indicators.

Diet, nutritional knowledge and health status of urban middle-aged Malaysian women.

The objective of the study was to assess nutritional and health status as well as nutritional knowledge in urban middle-aged Malaysian women. The impact of menopause on diet and health indices was also studied. The study included 360 disease free women, non users of HRT,aged > or =45 years with an intact uterus recruited from November 1999 to October 2001. Personal characteristics, anthropometric measurements and blood sample were acquired followed by clinical examination. Nutrient intake and nutritional knowledge was determined by a quantitative FFQ and KAP. The findings showed that urban middle-aged women, aged 51.65+/-5.40 years had energy intakes (EI) 11% below RDA, consisting of 53% carbohydrates, 15% protein and a 32% fat which declined with age. The sample which comprised of 42.5% postmenopausal women had a satisfactory diet and healthy lifestyle practices. Premenopausal women consumed more dietary fat (6%) with other aspects of diet comparable to the postmenopausal women. Iron intake was deficient in premenopausal women, amounting to 56% RDA contributing to a 26% prevalence of anaemia. Overall, calcium intake reached 440 mg daily but dairy products were not the main source. The postmenopaused had a more artherogenic lipid profile with significantly higher total cholesterol (TC) and LDL-C, but more premenopausal women were overweight/obese (49% versus 35%). EI was the strongest predictor for BMI and waist circumference (WC), with WC itself an independent predictor of fasting blood sugar and TC with BMI strongly affecting glucose tolerance. High nutritional knowledge was seen in 39% whereas 20% had poor knowledge. Newspapers and magazines, followed by the subject's social circle, were the main sources of nutritional information. Nutritional knowledge was positively associated with education, household income, vitamin/ mineral supplementation and regular physical activity but inversely related to TC. In conclusion, middle-aged urban women had an adequate diet with low iron and calcium intakes. Nutritional knowledge was positively associated to healthier lifestyle practices and lower TC. A comparable nutrient intake and lifestyle between pre and postmenopausal women suggested that health changes associated with menopause was largely independent of diet.

Predictors of intrauterine insemination success.

Intrauterine insemination (IUI) remains a therapeutic option within means of the majority of infertile couples in Malaysia. Therefore additional information on predictors of IUI success in the local context would provide a more concrete basis for counseling patients on expectations and treatment options. A retrospective analysis of 297 couples who underwent 445 IUI cycles from Jan 2005-Mar 2006 was undertaken. Four fifths were Malay with a mean paternal and maternal age of 35.53 +/- 5.82 (range 24-59) and 33.02 +/- 4.69 (range 21-46) years respectively. Causes of infertility were idiopathic (50%), endometriosis (17%) and anovulation/polycystic ovarian syndrome (15%). Almost 10% were oligoastenoteratozoospermic with another 23% oligozoospermic or astenozoospermic. Combined male and female factors occurred in 26%. A pregnancy rate (PR) of 9.4% per cycle; 14.1% per couple with a cumulative PR of 36.7% per 4 cycles was achieved. Those who became pregnant were significantly younger (31.29 +/- 4.43 vs. 33.21 +/- 4.68 years, p = 0.011) and had more follicles (13.95 +/- 9.72 vs. 11.43 +/- 6.67, p = 0.029) at the time of insemination. PR depreciated with maternal age and semen quality. Maternal and paternal age was inversely correlated to the number of follicles recruited (r = -0.30, p < 0.0005) and progressive sperm motility (r = -0.125, p = 0.013) respectively.

Bone health in urban midlife Malaysian women: risk factors and prevention.

The aim of this study was to identify risk factors associated with osteoporosis in urban midlife Malaysian women and to assess the effectiveness of lifestyle intervention in bone loss prevention with hormone replacement therapy (HRT) as a positive control. A total of 514 disease-free, uterus-intact, non-HRT-using women aged 45 years and older were recruited into the study. After initial bone mineral density (BMD) assessments, they were randomized into three groups: GI (control), G2 (lifestyle intervention), and G3 (lifestyle intervention with HRT). The study group was composed of 67.5% Chinese, 27.8% Malay, and 4.2% Indians with a mean age of 51.07+/-5.28 years. Two-fifths were postmenopausal, and the prevalence of osteoporosis was 24.1%, seen predominantly at the hip. Postmenopausal women had significantly lower mean BMD and a higher incidence of osteoporosis compared with the premenopausal women, 42.1% vs. 11.1% (p<0.0005). A lower incidence of osteoporosis was found in women who took calcium supplementation regularly as opposed to those who do not, 18.7% vs. 29.3% (p=0.036). Age and a greater postmenopausal duration showed a significant negative association with BMD, whereas higher family income, weight, body mass index, and waist and hip circumference were positively correlated. After 18-20 months, the effect of intervention was assessed based on BMD values of 279 women at baseline and after intervention. Lifestyle intervention alone was effective in premenopausal women, preventing over 90% of spinal bone loss compared with the controls, who lost 11.6% (0.046 g/cm2) bone mass with similar losses of hip bone, 2.0% (0.026 g/cm2) vs. 1.5% (0.020 g/cm2). Premenopausal women on HRT also showed a substantial decrease in spine and hip BMD, 18.6% (0.081 g/cm2) and 9.0% (0.122 g/cm2), respectively. The lifestyle intervention program retarded postmenopausal bone loss by 21% and 37% compared with controls, who lost 9.6% (0.141 g/cm2) and 6.0% (0.138 g/cm2) bone mass at the spine and hip. In comparison, lifestyle intervention with HRT increased postmenopausal BMD by 12.7% (0.216 g/cm2) at the spine and 1.9% (0.042 g/cm2) at the hip. The changes in hip BMD were influenced by current age, ethnicity, and income, while intervention had the strongest effect on spine BMD changes. In conclusion, lifestyle intervention prevented spinal bone loss in premenopausal women and retarded postmenopausal spine and hip bone loss compared with controls. The benefits of physical activity on spine and hip BMD highlight its potential as a safe and cost-effective alternative to HRT, which is not advocated because of its potential adverse effects.

Attojoule calorimetry of mesoscopic superconducting loops.

We report the first experimental evidence of nontrivial thermal behavior of the simplest mesoscopic system--a superconducting loop. By measuring the specific heat C of an array of 450,000 noninteracting aluminum loops with very high accuracy of approximately 20 fJ/K, we show that the loops go through a periodic sequence of phase transitions (with a period of an integer number of magnetic flux quanta) as the magnetic flux threading each loop is increased. The transitions are well described by the Ginzburg-Landau theory and are accompanied by discontinuities of C of only several thousands of Boltzmann constants kB.

Synchronous, bilateral breast cancer: prognostic value and incidence.

The purpose of this study was to address the question whether patients with bilateral breast cancer (BBC) have a worse prognosis in terms of recurrence and survival than patients with primarily unilateral breast cancer (UBC) following breast-conserving treatment (BCT). From 1983 to 2000, a total of 1760 BCT were registered in the Radiotherapy Department of the Medisch Spectrum Twente. We defined synchronous a BBC as cancer diagnosed in both breasts at the same time or within a period of 3 months of diagnosis of the first tumor. One thousand seven hundred and sixty BCT were performed on 1705 patients, 26 of whom presented with BBC. Of these 26 patients, 18 had BCT for both breasts. A higher proportion of patients with BBC showed more tubular carcinoma (P=0.029) and medially located tumors (P=0.076) than those with UBC did. The 5- and 10-year local recurrence rates (LRRs) were 4.5% and 9.1%, respectively, in BBC patients, as against 3.3% and 7.6% for UBC after BCT. The 5- and 10-year distant metastasis rates were 26.9% and 50.7%, respectively, for BBC as against 13.4% and 21.1% for UBC after BCT (P=0.065 and P=0.014, respectively). The 5- and 10-year disease-specific survival (DSS) rates for the 1705 patients were 82.1% and 41%, respectively, after BBC, and 91.4% and 84% after UBC (P=0.086 and P=0.0045, respectively). Patients with BBC have a higher rate of distant metastasis and a worse DSS than those with UBC. As the LRR is similar for BBC and UBC, BCT is not contraindicated in BBC. The incidence of BBC is low, at 1.5% which makes it difficult to reach any more definitive conclusions on outcome and treatment.

Prognostic factors in transitional cell cancer of the bladder: an emerging role for Bcl-2 and p53.

BACKGROUND AND PURPOSE: In a recent study on patients with transitional cell cancer of the bladder treated with curative radiotherapy following TUR-T, we demonstrated that a low apoptotic index and p53 positivity were associated with poor local control. The purpose of this study was to assess the prognostic significance of additional markers implicated in regulation of cell cycle and apoptosis. PATIENTS AND METHODS: Bcl-2, Bax and p21 positivity were detected immunohistochemically on paraffin-embedded pre-treatment biopsies from 83 patients with invasive transitional cell cancer (TCC) of the bladder, treated with radiotherapy. In addition, markers determined in an earlier analysis, i.e.: p53, apoptotic index, cyclin D1, retinoblastoma protein and Ki-67 were included in the multivariate analysis. A stepwise proportional hazard analysis was performed, adjusting for classic prognostic factors (T-stage, grade, multifocality and macroscopic completeness of the TUR). Positivity was defined as >10% of tumor cells staining positive for Bcl-2, Bax and p21, and >20% for p53. RESULTS: Bcl-2 positivity was found in 63%, Bax was positive in 52% and p21 in 55% of cases. In the PH analysis Bcl-2 positivity was found to be related to poor local control (36 vs. 72% at 3 years; P=0.003), as well as to shorter disease-specific survival (74 vs. 94% at 3 years; P=0.017). Evidence for an adverse effect of p53 positivity was also found (local control: 32 vs. 69% at 3 years;P=0.037, disease-specific survival: 76 vs. 92% at 3 years; P=0.043). In an additional PH analysis, we found poor local control rates for bladder cancers with combined Bcl-2 and p53 positivity (17 vs. 65% at 3 years; P=0.0017), and lower disease specific survival (60 vs. 92%; P=0.0024), disease-free survival (7 vs.35%, P=0.0023) and overall survival (39 vs. 80%; P=0.0018). CONCLUSION: This study provides evidence for a poor outcome in patients treated with radiotherapy for TCC of the bladder expressing both Bcl-2 and p53. This relationship was found for local control and disease-free, disease-specific and overall survival.

Apoptosis, proliferation and p53, cyclin D1, and retinoblastoma gene expression in relation to radiation response in transitional cell carcinoma of the bladder.

PURPOSE: To determine whether the apoptotic index, the Ki67 index, and the expression of the p53, cyclin D1, and retinoblastoma genes correlate with local control, overall survival, and time to distant metastases in invasive bladder cancer treated with external beam radiation. METHODS AND MATERIALS: Paraffin-embedded pretreatment biopsies from 83 patients with invasive transitional cell carcinoma of the bladder were scored morphologically for apoptosis and immunohistochemically for Ki67, p53, cyclin D1, and retinoblastoma gene expression. Survival analysis methods were used to assess overall survival, local control, and freedom from distant metastases. A multiple proportional hazard (PH) regression analysis was performed to study the prognostic value of the abovementioned biologic parameters (all divided into two categories, except Ki67) in addition to classical prognostic factors such as T stage, histologic grade, multifocality of the tumor, and completeness of transurethral resection. All patients were treated with external beam radiation as sole treatment. Median follow-up for the 19 patients still living was 7.5 years. RESULTS: Apoptotic index varied from 0% to 3.4% with a mean of 0.8% and a median of 0.6%. Ki67 index varied from 0% to 60% with a mean of 14% and a median of 12%. P53 protein was detectable in 61% of the tumors. Overexpression of cyclin D1 was observed in 39% of the tumors and loss of retinoblastoma protein in 23% of the tumors. High Ki67 index was found to be significantly associated with p53 expression (p = 0.04) and cyclin D1 overexpression (p = 0.023). Cyclin D1 overexpression was found more often in Rb-positive tumors than in Rb-negative tumors (p = 0.006). Other associations between the markers are less clear. Biologic markers were not correlated with T stage or grade. In the PH analysis local control was found to be significantly better for tumors with wild-type p53 (p = 0.028). Also, tumors with an apoptotic index above the median value (0.6%) had a significantly better local control rate (p = 0.035). Ki67 index (p = 0.35), retinoblastoma gene expression (p = 0.30) and cyclin D1 overexpression (p = 0.61) were not found to have an additional predictive value regarding local tumor control. None of the tested biologic parameters were found to be associated with overall survival. Time to distant metastases was significantly shorter for tumors with high Ki67 index (p = 0.01) and tumors with an apoptotic index less than median (p = 0.009). CONCLUSIONS: The results of our study provide evidence for a prognostic value of p53 expression and apoptotic index with respect to the radiation response in bladder cancer in addition to more conventional prognosticators. The value of these parameters as a predictive assay for radiation response warrants confirmation in larger and prospective studies.