The PARTNER trial of neoadjuvant olaparib with chemotherapy in triple-negative breast cancer.

PARTNER is a prospective, phase II-III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer1,2, who were germline BRCA1 and BRCA2 wild type3. Here we report the results of the trial. Patients (n = 559) were randomized on a 1:1 basis to receive neoadjuvant carboplatin-paclitaxel with or without 150 mg olaparib twice daily, on days 3 to 14, of each of four cycles (gap schedule olaparib, research arm) followed by three cycles of anthracycline-based chemotherapy before surgery. The primary end point was pathologic complete response (pCR)4, and secondary end points included event-free survival (EFS) and overall survival (OS)5. pCR was achieved in 51% of patients in the research arm and 52% in the control arm (P = 0.753). Estimated EFS at 36 months in the research and control arms was 80% and 79% (log-rank P > 0.9), respectively; OS was 90% and 87.2% (log-rank P = 0.8), respectively. In patients with pCR, estimated EFS at 36 months was 90%, and in those with non-pCR it was 70% (log-rank P < 0.001), and OS was 96% and 83% (log-rank P < 0.001), respectively. Neoadjuvant olaparib did not improve pCR rates, EFS or OS when added to carboplatin-paclitaxel and anthracycline-based chemotherapy in patients with triple-negative breast cancer who were germline BRCA1 and BRCA2 wild type. ClinicalTrials.gov ID: NCT03150576 .

Paclitaxel plus Eftilagimod Alpha, a Soluble LAG-3 Protein, in Metastatic, HR+ Breast Cancer: Results from AIPAC, a Randomized, Placebo Controlled Phase IIb Trial.

PURPOSE: Eftilagimod alpha (efti), a soluble lymphocyte activation gene (LAG-3) protein and MHC class II agonist, enhances innate and adaptive immunity. Active Immunotherapy PAClitaxel (AIPAC) evaluated safety and efficacy of efti plus paclitaxel in patients with predominantly endocrine-resistant, hormone receptor-positive, HER2-negative metastatic breast cancer (ET-resistant HR+ HER2- MBC). PATIENTS AND METHODS: Women with HR+ HER2- MBC were randomized 1:1 to weekly intravenous paclitaxel (80 mg/m2) and subcutaneous efti (30 mg) or placebo every 2 weeks for six 4-week cycles, then monthly subcutaneous efti (30 mg) or placebo maintenance. Primary endpoint was progression-free survival (PFS) by blinded independent central review. Secondary endpoints included overall survival (OS), safety/tolerability, pharmacokinetics/pharmacodynamics, and quality of life. Exploratory endpoints included cellular biomarkers. RESULTS: 114 patients received efti and 112 patients received placebo. Median age was 60 years (91.6% visceral disease, 84.1% ET-resistant, 44.2% with previous CDK4/6 inhibitor treatment). Median PFS at 7.3 months was similar for efti and placebo. Median OS was not significantly improved for efti (20.4 vs. 17.5 months; HR, 0.88; P = 0.197) but became significant for predefined exploratory subgroups. EORTC QLQC30-B23 global health status was sustained for efti but deteriorated for placebo. Efti increased absolute lymphocyte, monocyte and secondary target cell (CD4, CD8) counts, plasma IFNγ and CXCL10 levels. CONCLUSIONS: Although the primary endpoint, PFS, was not met, AIPAC confirmed expected pharmacodynamic effects and demonstrated excellent safety profile for efti. OS was not significantly improved globally (2.9-month difference), but was significantly improved in exploratory biomarker subgroups, warranting further studies to clarify efti's role in patients with ET-resistant HER2- MBC.

Mitigating Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: Ameliorating Sexual Function and Psychological Well-Being in Older Men.

This study aimed to investigate the prevalence of lower urinary tract symptoms (LUTS) in older men (N= 3056) with benign prostatic hyperplasia (BPH) and its effects on their sexual function and mental health. Descriptive, correlation, and regression analyses were used to explore the relationships between prostate and lower urinary tract health and psychological well-being. Better prostate and lower urinary tract health positively affected psychological well-being, and sexual function also had a positive influence. LUTS have an adverse impact on sexual function and mental health. Early intervention is crucial for mitigating the negative impact of LUTS on the quality of life in older men. Addressing prostate and lower urinary tract health issues through appropriate interventions may improve psychological well-being. Health care professionals must consider the adverse effects of BPH and LUTS on sexual function and mental health, and implement interventions to enhance the overall quality of life in older men.

The frequency and clinical significance of centromere enumeration probe 17 alterations in human epidermal growth factor receptor 2 immunohistochemistry-equivocal invasive breast cancer.

BACKGROUND AND AIMS: Chromosome 17 alterations affect the assessment of HER2 gene amplification in breast cancer (BC), but its clinical significance remains unclear. This study aimed to identify the prevalence of centromere enumeration probe 17 (CEP17) alterations, and its correlation with response to neoadjuvant therapy (NAT) in BC patients with human epidermal growth factor receptor 2 (HER2) immunohistochemistry-equivocal score. METHODS AND RESULTS: A large BC cohort (n = 6049) with HER2 immunohistochemistry score 2+ and florescent in-situ hybridisation (FISH) results was included to assess the prevalence of CEP17 alterations. Another cohort (n = 885) with available clinicopathological data was used to evaluate the effect of CEP17 in the setting of NAT. HER2-amplified tumours with monosomy 17 (CEP17 copy number < 1.5 per nucleus), normal 17 (CEP17 1.5-< 3.0) and polysomy 17 (CEP17 ≥ 3.0) were observed in 16, 59 and 25%, respectively, compared with 3, 74 and 23%, respectively, in HER2-non-amplified tumours. There was no significant relationship between CEP17 alterations and pathological complete response (pCR) rate in both HER2-amplified and HER2-non-amplified tumours. The independent predictors of pCR were oestrogen (ER) negativity in HER2-amplified tumours [ER negative versus positive; odds ratio (OR) = 11.80; 95% confidence interval (CI) = 1.37-102.00; P = 0.02], and histological grade 3 in HER2 non-amplified tumours (3 versus 1, 2; OR = 5.54; 95% CI = 1.61-19.00; P = 0.007). CONCLUSION: The impacts of CEP17 alterations are not as strong as those of HER2/CEP17 ratio and HER2 copy number. The hormonal receptors status and tumour histological grade are more useful to identify BC patients with a HER2 immunohistochemistry-equivocal score who would benefit from NAT.

Role of front-line bevacizumab in advanced ovarian cancer: the OSCAR study.

OBJECTIVE: Two randomized phase III trials demonstrated the efficacy and safety of combining bevacizumab with front-line carboplatin/paclitaxel for advanced ovarian cancer. The OSCAR (NCT01863693) study assessed the impact of front-line bevacizumab-containing therapy on safety and oncologic outcomes in patients with advanced ovarian cancer in the UK. METHODS: Between May 2013 and April 2015, patients with high-risk stage IIIB-IV advanced ovarian cancer received bevacizumab (7.5 or 15 mg/kg every 3 weeks, typically for ≤12 months, per UK clinical practice) combined with front-line chemotherapy, with bevacizumab continued as maintenance therapy. Co-primary endpoints were progression-free survival and safety (NCI-CTCAE v4.0). Patients were evaluated per standard practice/physician's discretion. RESULTS: A total of 299 patients received bevacizumab-containing therapy. The median age was 64 years (range 31-83); 80 patients (27%) were aged ≥70 years. Surgical interventions were primary debulking in 21%, interval debulking in 36%, and none in 43%. Most patients (93%) received bevacizumab 7.5 mg/kg with carboplatin/paclitaxel. Median duration of bevacizumab was 10.5 months(range <0.1-41.4); bevacizumab and chemotherapy were given in combination for a median of three cycles (range 1-10). Median progression-free survival was 15.4 (95% CI 14.5 to 16.9) months. Subgroup analyses according to prior surgery showed median progression-free survival of 20.8, 16.1, and 13.6 months in patients with primary debulking, interval debulking, and no surgery, respectively. Median progression-free survival was 16.1 vs 14.8 months in patients aged <70 versus ≥70 years, respectively. The 1-year overall survival rate was 94%. Grade 3/4 adverse events occurred in 54% of patients, the most common being hypertension (16%) and neutropenia (5%). Thirty-five patients (12%) discontinued bevacizumab for toxicity (most often for proteinuria (2%)). CONCLUSIONS: Median progression-free survival in this study was similar to that in the high-risk subgroup of the ICON7 phase III trial. Median progression-free survival was shortest in patients who did not undergo surgery.

Blessing or burden? Long-term maintenance, complications and clinical outcome of intrathecal baclofen pumps.

AIM: The intrathecal baclofen pump is an effective treatment for spasticity. However, long-term results have reported patients' dissatisfaction and perception of disability. Potential causes include a frequent need for baclofen pump refill and risks of complications. The aim of the present study was to evaluate the long-term maintenance, complications and clinical outcome of intrathecal baclofen pumps. PATIENTS AND METHODS: We conducted a 16-year retrospective cohort study of patients with spasticity treated with an intrathecal baclofen pump at a university hospital from 2000 to 2016. The primary outcome was the rate of infection per puncture for baclofen pump refill. Secondary outcomes included the incidence of other complications, such as running out of baclofen causing symptomatic withdrawal symptoms, pump mechanical failure, pump battery end of life and the need for pump replacement. The clinical outcome was assessed by the Modified Ashworth Scale (mAS). RESULTS: In total, 340 follow-up episodes with pump refill procedures were recorded. The average interval between each pump refill was 57.3 days (±15.4 days). The average duration of admission for each pump refill was 4 h and 49 min (from 2 h 23 min to 10 h). There were two events with established infection after puncture for the refill, giving rise to an infection rate per puncture of 0.6 percent (2/340).For the long-term clinical outcome, at an average follow-up period of 7.6 years, the postoperative mAS for spasticity was 2.0 ± 0.756, which was significantly better than the preoperative mAS at 3.75 ± 0.462 (P = 0.001). CONCLUSION: Long-term aftercare with baclofen pump refill was safe, with an infection rate of 0.6 per cent per puncture for each refill. Long-term intrathecal baclofen pump was effective in the treatment of spasticity with persistent significant improvement in the spasticity scale.

Emerging therapies for acute myeloid leukemia: translating biology into the clinic.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a poor outcome; overall survival is approximately 35% at two years and some subgroups have a less than 5% two-year survival. Recently, significant improvements have been made in our understanding of AML biology and genetics. These fundamental discoveries are now being translated into new therapies for this disease. This review will discuss recent advances in AML biology and the emerging treatments that are arising from biological studies. Specifically, we will consider new therapies that target molecular mutations in AML and dysregulated pathways such as apoptosis and mitochondrial metabolism. We will also discuss recent advances in immune and cellular therapy for AML.

Use of the International Prostate Symptom Score (IPSS) in Chinese male patients with benign prostatic hyperplasia.

PURPOSE: To test the psychometric properties of the International Prostate Symptom Score (Hong Kong Chinese version 2) (IPSS) in Chinese male patients with benign prostatic hyperplasia (BPH) under secondary care. METHODS: A prospective longitudinal study was done by interviewing subjects at baseline, at 2 week after baseline for assessing test-retest reliability and at 26 week after baseline for assessing responsiveness. All subjects were interviewed to complete a structured questionnaire including IPSS, Short Form-12 Health Survey version 2 (SF-12v2) and Depression Anxiety Stress Scale (DASS). RESULTS: The IPSS HRQOL score had weak correlations with SF-12v2 summary and DASS domain scores. For reliability analysis, Cronbach's alpha coefficient was 0.90 for the seven symptom-related items. The intraclass correlation coefficients of the IPSS total symptom score and HRQOL score were 0.90 and 0.86, respectively. For sensitivity, statistically significant differences were detected between the subjects with BPH and those without for IPSS total symptom score (effect size = 0.68) but not the IPSS HRQOL score. The areas under ROC curves for the IPSS total symptom and HRQOL scores were 0.67 and 0.60, respectively. CONCLUSIONS: The IPSS was valid, reliable instrument in Chinese patients with BPH. The IPSS total symptom score, but not the HRQOL score, is sensitive in differentiating subgroups.

Outcome and prognostic factors in 110 consecutive patients with primary uterine leiomyosarcoma: A Rare Cancer Network study.

OBJECTIVE: Primary uterine leiomyosarcomas (ULMS) are rare, and the optimal treatment is controversial. We aimed to assess the outcome and prognostic factors in a multicenter population of women treated for primary ULMS. METHODS: We retrospectively collected data of 110 women treated in 19 institutions of the Rare Cancer Network (RCN). Inclusion criteria consisted of a pathology report confirming the diagnosis of ULMS, aged 18-80 years, complete International Federation of Gynecology and Obstetrics (FIGO) stage information, complete information on treatment, and a minimum follow-up of 6 months. Local control (LC) and locoregional control (LRC), overall survival (OS) and disease-free survival (DFS) rates were computed using the Kaplan-Meier method. Univariate analysis was implemented using the log rank test, and multivariate analysis using the Cox model. RESULTS: All patients underwent surgery. Seventy-five patients (68%) received adjuvant radiotherapy (RT), including brachytherapy in 18 (16%). Seventeen patients (15%) received adjuvant chemotherapy. Median follow-up was 58 (range, 6-240) months. Five-year OS and DFS rates were 50% and 34%, and LC and LRC rates were 88% and 72%, respectively. On multivariate analysis, independent favorable prognostic factors were younger age, FIGO stage I, small tumor size, previous uterine disease, and no vascular invasion for OS and DFS. FIGO stage was the only favorable factor influencing LRC. Adjuvant local or systemic treatments did not improve the outcomes. Eight patients treated with RT presented a grade 3 acute toxicity, and only one patient with grade 3 late toxicity. CONCLUSIONS: In this large population of primary ULMS patients, we found good results in terms of LC and LRC. Nevertheless, OS remains poor, mainly due to the occurrence of distant metastases. An early diagnosis seemed to improve the prognosis of the patients. Adjuvant local or systemic treatments, or more aggressive surgical procedures such as the Wertheim procedure, did not seem to impact the outcome.

SRC3 Phosphorylation at Serine 543 Is a Positive Independent Prognostic Factor in ER-Positive Breast Cancer.

PURPOSE: The steroid receptor coactivator SRC3 is essential for the transcriptional activity of estrogen receptor α (ERα). SRC3 is sufficient to cause mammary tumorigenesis, and has also been implicated in endocrine resistance. SRC3 is posttranslationally modified by phosphorylation, but these events have not been investigated with regard to functionality or disease association. Here, we investigate the spatial selectivity of SRC3-pS543/DNA binding over the human genome and its expression in primary human breast cancer in relation with outcome. EXPERIMENTAL DESIGN: Chromatin immunoprecipitation, coupled with sequencing, was used to determine the chromatin binding patterns of SRC3-pS543 in the breast cancer cell line MCF7 and two untreated primary breast cancers. IHC was used to assess the expression of SRC3 and SRC3-pS543 in 1,650 primary breast cancers. The relationship between the expression of SRC3 and SRC3-pS543, disease-free survival (DFS), and breast cancer specific survival (BCSS) was assessed. RESULTS: Although total SRC3 is selectively found at enhancer regions, SRC3-pS543 is recruited to promoters of ERα responsive genes, both in the MCF7 cell line and primary breast tumor specimens. SRC3-pS543 was associated with both improved DFS (P = 0.003) and BCSS (P = 0.001) in tamoxifen untreated high-risk patients, such a correlation was not seen in tamoxifen-treated cases, the interaction was statistically significant (P = 0.001). Multivariate analysis showed SRC3-pS543 to be an independent prognostic factor. CONCLUSIONS: Phosphorylation of SRC3 at S543 affects its genomic interactions on a genome-wide level, where SRC3-pS543 is selectively recruited to promoters of ERα-responsive genes. SRC3-pS543 is a prognostic marker, and a predictive marker of response to endocrine therapy.

Inflammatory myofibroblastic tumours of the urinary bladder: multi-centre 18-year experience.

OBJECTIVE: To review a series of inflammatory myofibroblastic tumours (IMTs) of the urinary bladder in 10 hospitals in Hong Kong. METHODS: A database search in the pathology archives of 10 hospitals in Hong Kong from 1995 to 2013 was performed using the key words 'inflammatory myofibroblastic tumour', 'inflammatory pseudotumour' and 'spindle cell lesion'. Patient characteristics, clinical features, histological features, immunohistochemical staining results and treatment outcomes were reviewed. RESULTS: Nine cases of IMT of the urinary bladder were retrieved. The mean age was 45.4 ± 22.8 years (range 11-78). Eight patients (88.9%) presented with haematuria and 5 patients (55.6%) had anaemia with a mean haemoglobin level of 6.8 ± 1.3 g/dl. Histologically, the majority of patients (77.8%) had a compact spindle cell pattern. Anaplastic lymphoma kinase staining was positive in 75% of cases. During a mean follow-up period of 43.4 months (range 8-94), none of them developed any local recurrence or distant metastasis. CONCLUSIONS: A high index of suspicion of IMT should be maintained for young patients presenting with bleeding bladder tumours and significant anaemia. IMTs of the urinary bladder run a benign disease course, and good prognosis can be achieved after surgical resection.

Heat Damage Zones Created by Different Energy Sources Used in the Treatment of Benign Prostatic Hyperplasia in a Pig Liver Model.

INTRODUCTION: There are different types of transurethral prostatic surgeries and the complication profiles are different. This study aims to compare the heat damage zones (HDZ) created by five different technologies in a pig liver model. MATERIALS AND METHODS: Monopolar resection, bipolar resection, electrovaporization, and Greenlight™ lasers of 120 and 180 W were used to remove fresh pig liver tissue in a simulated model. Each procedure was repeated in five specimens. Two blocks were selected from each specimen to measure the three deepest HDZ. RESULTS: The mean of HDZ was 295, 234, 192, 673, and 567 µm, respectively, for monopolar resection, bipolar resection, electrovaporization, Greenlight laser 120 W, and Greenlight laser 180 W, respectively. The Greenlight laser produced one to three times deeper HDZ than the other energy sources (p=0.000). CONCLUSION: Both 120 and 180 W Greenlight lasers produced deeper HDZ than the other energy sources. Urologists need to be aware of HDZ that cause tissue damage outside the operative field.

Phosphorylation of activating transcription factor-2 (ATF-2) within the activation domain is a key determinant of sensitivity to tamoxifen in breast cancer.

Activating transcription factor-2 (ATF-2) has been implicated as a tumour suppressor in breast cancer (BC). c-JUN N-terminal kinase (JNK) and p38 MAPK phosphorylate ATF-2 within the activation domain (AD), which is required for its transcriptional activity. To date, the role of ATF-2 in determining response to endocrine therapy has not been explored. Effects of ATF-2 loss in the oestrogen receptor (ER)-positive luminal BC cell line MCF7 were explored, as well as its role in response to tamoxifen treatment. Genome-wide chromatin binding patterns of ATF-2 when phosphorylated within the AD in MCF-7 cells were determined using ChIP-seq. The expression of ATF-2 and phosphorylated ATF-2 (pATF-2-Thr71) was determined in a series of 1,650 BC patients and correlated with clinico-pathological features and clinical outcome. Loss of ATF-2 diminished the growth-inhibitory effects of tamoxifen, while tamoxifen treatment induced ATF-2 phosphorylation within the AD, to regulate the expression of a set of 227 genes for proximal phospho-ATF-2 binding, involved in cell development, assembly and survival. Low expression of both ATF-2 and pATF-2-Thr71 was significantly associated with aggressive pathological features. Furthermore, pATF-2 was associated with both p-p38 and pJNK1/2 (< 0.0001). While expression of ATF-2 is not associated with outcome, pATF-2 is associated with longer disease-free (p = 0.002) and BC-specific survival in patients exposed to tamoxifen (p = 0.01). Furthermore, multivariate analysis confirmed pATF-2-Thr71 as an independent prognostic factor. ATF-2 is important for modulating the effect of tamoxifen and phosphorylation of ATF-2 within the AD at Thr71 predicts for improved outcome for ER-positive BC receiving tamoxifen.

Ductal adenocarcinoma of the prostate: a Hong Kong case series.

OBJECTIVES: To review and report our local experience in the management of ductal adenocarcinoma of the prostate. METHODS: Retrospective review of patients diagnosed with ductal adenocarcinoma of the prostate in two regional urological centres in Hong Kong during 1995-2009. Clinical information, treatment and outcomes were retrieved for further analysis. RESULTS: We identified 19 Chinese patients diagnosed with ductal adenocarcinoma of the prostate. Majority of our patients presented with retention of urine and haematuria. At presentation, seven patients were already at an advanced stage with evidence of rectal invasion or distant metastasis. The overall treatment outcome was poor with high failure rate after either local or systemic hormonal therapy. CONCLUSION: We observed a predilection of this tumour to be locally aggressive, and hence a relatively high incidence of intra-luminal growth and rectal invasion. We observed a high failure rate after either radical prostatectomy or hormonal therapy.

Pre-operative tumor localization and evaluation of extra-capsular extension of prostate cancer: how misleading can it be?

PURPOSE: To verify the accuracy of transrectal ultrasound-guided prostatic biopsy (TRUS Bx), magnetic resonance imaging (MRI) and their combination in evaluating the laterality of prostate cancer and to determine the accuracy of MRI in assessing extra-capsular extension of prostate cancer. MATERIALS AND METHODS: We retrospectively reviewed our past 100 consecutive series of radical prostatectomy performed between February 2010 and April 2012 at our institution. Their TRUS Bx and MRI results were compared with the pathology of the radical prostatectomy specimens. For tumor localization, we calculated the accuracies in unilateral diseases, bilateral diseases, overall accuracies and Cohen Kappa concordance coefficient of TRUS Bx, MRI and their combination. For the assessment of extra-capsular extension, we calculated the sensitivity, specificity, positive predictive value, negative predictive value, overall accuracy, likelihood ratio positive and likelihood ratio negative of MRI. RESULTS: Eighty-two percent of our radical prostatectomy specimens had bilateral tumor involvement and 32% had extra-capsular extension. The accuracies of TRUS Bx in unilateral disease, bilateral disease and overall accuracy were 15.2%, 91.4% and 43.6%, respectively. The accuracies of MRI in unilateral disease, bilateral disease and overall accuracy were 11.1%, 66.7% and 38.9%, respectively. When combining the assessment of TRUS Bx and MRI, the accuracies in unilateral disease, bilateral disease and overall accuracy were 16.7%, 75% and 55.6%, respectively. The Cohen Kappa concordance co-efficient of TRUS Bx, MRI, and combination of them were 0.1165, -0.2047 and -0.1084, respectively. The positive predictive value, negative predictive value, sensitivity, specificity, overall accuracy, likelihood ratio positive and likelihood ratio negative of MRI in assessing extra-capsular extension were 33.3%, 69.8%, 5.9%, 94.9%, 67.9%, 1.16 and 0.99, respectively. CONCLUSION: TRUS Bx, MRI, and their combination had poor concordance and limited accuracies in assessment of the laterality of tumor involvement. The combination of TRUS Bx and MRI offered a better of accuracy when compared to either modality alone. MRI was a specific, but not sensitive tool in assessing the presence of extra-capsular extension.

A prospective study comparing bipolar endoscopic enucleation of prostate with bipolar transurethral resection in saline for management of symptomatic benign prostate enlargement larger than 70 g in a matched cohort.

PURPOSE: This study aims to compare the efficacy and safety of bipolar endoscopic enucleation of prostate with transurethral resection in saline for large BPE greater than 70 g. METHODS: All patients from two urology centres who had bipolar enucleation or bipolar resection performed for large BPE greater than 70 g from December 2008 to April 2012 were prospectively assessed. The pre-operative and post-operative measures included IPSS, QOL score, uroflowmetry results, PSA and prostate volume. The perioperative measures were compared, and the post-operative complications/resumption of medical treatment for lower urinary tract symptoms were also assessed. RESULTS: There were 74 and 86 consecutive patients with bipolar enucleation and bipolar resection performed, respectively. No difference in pre-operative characteristics was observed between the two groups with mean prostate size 115 cc in each group. Comparing bipolar enucleation with bipolar resection, there was longer operative time (156 vs 87 min, p = 0.000), more haemoglobin drop (1.8 vs 1.1 g/dL, p = 0.006), but more prostate tissue resected (61.4 vs 45.7 g, p = 0.000). There was no difference in overall transfusion requirement and hospital stay. At 12 month after the procedure, patients with bipolar enucleation performed had better IPSS (6.4 vs 11.6, p = 0.032), QOL (1.7 vs 2.6, p = 0.040) and peak flow rate (19.5 vs 15.1 ml/s, p = 0.019). The post-operative complications had no significant difference between the two groups. CONCLUSIONS: For surgical treatment of big BPE, bipolar endoscopic enucleation of prostate provided superior functional outcome than bipolar resection but required longer operative time.

Are preoperative Kattan and Stephenson nomograms predicting biochemical recurrence after radical prostatectomy applicable in the Chinese population?

PURPOSE: Kattan and Stephenson nomograms are based on the outcomes of patients with prostate cancer recruited in the USA, but their applicability to Chinese patients is yet to be validated. We aim at studying the predictive accuracy of these nomograms in the Chinese population. PATIENTS AND METHODS: A total of 408 patients who underwent laparoscopic or open radical resection of prostate from 1995 to 2009 were recruited. The preoperative clinical parameters of these patients were collected, and they were followed up regularly with PSA monitored. Biochemical recurrence was defined as two or more consecutive PSA levels >0.4 ng/mL after radical resection of prostate or secondary cancer treatment. RESULTS: The overall observed 5-year and 10-year biochemical recurrence-free survival rates were 68.3% and 59.8%, which was similar to the predicted values by the Kattan and Stephenson nomograms, respectively. The results of our study achieved a good concordance with both nomograms (Kattan: 5-years, 0.64; Stephenson: 5-years, 0.62, 10-years, 0.71). CONCLUSIONS: The incidence of prostate cancer in Hong Kong is increasing together with the patients' awareness of this disease. Despite the fact that Kattan nomograms were derived from the western population, it has been validated in our study to be useful in Chinese patients as well.

Variation in telangiectasia predisposing genes is associated with overall radiation toxicity.

PURPOSE: In patients receiving radiotherapy for breast cancer where the heart is within the radiation field, cutaneous telangiectasiae could be a marker of potential radiation-induced heart disease. We hypothesized that single nucleotide polymorphisms (SNPs) in genes known to cause heritable telangiectasia-associated disorders could predispose to such late, normal tissue vascular damage. METHODS AND MATERIALS: The relationship between cutaneous telangiectasia as a late normal tissue radiation injury phenotype in 633 breast cancer patients treated with radiotherapy was examined. Patients were clinically assessed for the presence of cutaneous telangiectasia and genotyped at nine SNPs in three candidate genes. Candidate SNPs were within the endoglin (ENG) and activin A receptor, type II-like 1 (ACVRL1) genes, mutations in which cause hereditary hemorrhagic telangiectasia and the ataxia-telangiectasia mutated (ATM) gene associated with ataxia-telangiectasia. RESULTS: A total of 121 (19.1%) patients exhibited a degree of cutaneous telangiectasiae on clinical examination. Regression was used to examine the associations between the presence of telangiectasiae in patients who underwent breast-conserving surgery, controlling for the effects of boost and known brassiere size (n=388), and individual geno- or haplotypes. Inheritance of ACVRL1 SNPs marginally contributed to the risk of cutaneous telangiectasiae. Haplotypic analysis revealed a stronger association between inheritance of a ATM haplotype and the presence of cutaneous telangiectasiae, fibrosis and overall toxicity. No significant association was observed between telangiectasiae and the coinheritance of the candidate ENG SNPs. CONCLUSIONS: Genetic variation in the ATM gene influences reaction to radiotherapy through both vascular damage and increased fibrosis. The predisposing variation in the ATM gene will need to be better defined to optimize it as a predictive marker for assessing radiotherapy late effects.

Association between single nucleotide polymorphisms in the DNA repair gene LIG3 and acute adverse skin reactions following radiotherapy.

Many genes have been associated with radiotherapy toxicity, but most have only been found in a single study. Using our cohort of 480 breast cancer patients, we provide replicated evidence that a polymorphism near the LIG3 gene is associated with acute skin toxicity following radiotherapy.