Outcomes of Dose-Attenuated Docetaxel in Asian Patients with Castrate-Resistant Prostate Cancer

<p><b>INTRODUCTION</b>High levels of toxicities have been observed when docetaxel is administered at the standard dose of 75 mg/mevery 3 weeks (Q3W) in the real-world treatment of Asian patients with metastatic castrate-resistant prostate cancer (CRPC). This study aimed to evaluate the efficacy and tolerability of 2 attenuated regimens more widely used in an Asian setting to minimise toxicity - 60 mg/mQ3W and weekly docetaxel (20 mg/mto 35 mg/m).</p><p><b>MATERIALS AND METHODS</b>Medical records of 89 CRPC patients between December 2003 and April 2013 were reviewed. Pairwise statistical analysis was performed, comparing efficacy and safety outcomes of 75 mg/mQ3W and weekly docetaxel with 60 mg/mQ3W. Treatment endpoints used were prostate-specific antigen (PSA) response (decrease of ≥50% from baseline), pain improvement after cycle 2, overall survival, time to disease progression and radiological response.</p><p><b>RESULTS</b>Patients who received docetaxel at 75 mg/mQ3W were younger than those who received 60 mg/mQ3W (62 years and 66 years, respectively;= 0.0489). Both groups had similar response rates. Compared with patients on 60 mg/mQ3W, more patients on weekly regimens were symptomatic at baseline (63.2% and 87.5%, respectively;= 0.0173). Longer overall survival was observed in the 60 mg/mQ3W arm than the weekly docetaxel arm (16.9 months and 10.6 months, respectively;= 0.0131), though other measures of response did not differ significantly.</p><p><b>CONCLUSION</b>Our data supports the use of 60 mg/mQ3W docetaxel which has similar efficacy and an acceptable toxicity profile compared to the standard 75 mg/mQ3W regimen. Weekly docetaxel has significant palliative benefits among symptomatic patients despite lower overall survival.</p>

Differential radiologic characteristics of renal tumours on multiphasic computed tomography

<p><b>INTRODUCTION</b>This study analysed the tumour attenuation characteristics of different subtypes of renal cell carcinomas (RCCs), including clear cell RCC (ccRCC), papillary RCC (pRCC), mixed RCC, chromophobe RCC (chRCC) and oncocytoma.</p><p><b>METHODS</b>We randomly selected 100 RCC cases that underwent nephrectomy between 2004 and 2012 from a collaborative database. Of these cases, 36 were excluded due to the absence of available imaging. The remaining 64 cases comprised 35 ccRCCs, 11 pRCCs, eight chRCCs, seven mixed RCCs and three oncocytomas. The cases were classified as computed tomography (CT) kidney, CT urogram (with plain, nephrographic and pyelographic phases) or CT abdomen (with portovenous and delayed phases). A circular region of interest (ROI) ≥ 1 cmwas drawn and the same standard ROI size was used for each phase at the same site; three different circular ROIs were drawn per lesion per phase. Analysis of variance and t-test were used to examine differences in the radiological characteristics.</p><p><b>RESULTS</b>There was no statistical difference in the attenuation and degree of enhancement between mixed RCCs and ccRCCs. The attenuation and degree of enhancement of the oncocytomas were significantly higher than those of the other RCC subtypes.</p><p><b>CONCLUSION</b>While mixed RCCs did not have attenuation characteristics that differed significantly from those of ccRCCs, oncocytomas can be distinguished from ccRCCs, pRCCs, chRCCs and mixed RCCs by their high radiological density and enhancement. The ability to differentiate oncocytomas from these tumours potentially allows the preoperative selection of patients with small renal masses for conservative management.</p>

Assessment of the American Joint Committee on Cancer 7th edition staging for localised prostate cancer in Asia treated with external beam radiotherapy

<p><b>INTRODUCTION</b>Most international clinical practice guidelines for prostate cancer (PCa) are driven by data derived in a Western setting. However, tumour biology and clinical disease progression are likely to differ in the Asian population. We compare the performance of the revised American Joint Committee on Cancer (AJCC) prognostic groups with the commonly used D'Amico Risk Classification and conventional predictors for PCa, in a large cohort of Asian patients.</p><p><b>MATERIALS AND METHODS</b>We retrospectively reviewed data for 404 consecutive Singaporean patients receiving definitive radiotherapy at our centre between December 1996 and October 2006. The primary outcome was biochemical relapse-free survival (BRFS), defined using the Phoenix definition. The secondary outcome was overall survival (OS). Prognostic risk groups were defined using AJCC 7th edition (AJCC7) and 6th edition (AJCC6). Univariate analysis (UVA) and multivariate analysis (MVA) were performed for the following putative risk factors: age, Gleason score, prognostic grouping, tumour classification, radiation delivery technique, radiotherapy dose, hormonal therapy and initial PSA value.</p><p><b>RESULTS</b>For the cohort, median age was 69 years. Median follow-up was 66.3 months. Five-year BRFS rate was 84.3% with 71 biochemical relapses and 5-year OS rate was 89.1% with 54 deaths. The concordance-indices for BRFS prediction were 0.588, 0.550 and 0.567 for AJCC7, AJCC6 and D'Amico respectively. Initial PSA, T-stage and AJCC7 were prognostic for BRFS on UVA. Comparison of AJCC7 vs. D'Amico showed no statistical additional value of either classification system although D'Amico was superior when compared to AJCC6 in predicting BRFS. T-stage ≥3 and D'Amico were significant prognostic factors for BRFS on MVA.</p><p><b>CONCLUSION</b>In our local, predominantly Chinese population, neither AJCC6 nor AJCC7 demonstrated a high predictive accuracy for BRFS although AJCC7 has a slightly better predictive ability than AJCC6.</p>

Prospective audit of post-chemotherapy febrile neutropenia in patients with solid cancer and lymphoma in two Singaporean cancer centres

<p><b>INTRODUCTION</b>Febrile neutropenia (FN) is a significant cause of mortality and morbidity in oncology and haematology units worldwide. The overall mortality in hospital surveys in Singapore surveys on post-chemotherapy FN has ranged between 3.0% and 8.8%. However, recent evidence indicates that outpatient management of patients with low-risk FN is safe and cost-effective.</p><p><b>MATERIALS AND METHODS</b>We conducted a prospective audit on a cohort of adult patients with post-chemotherapy FN seen at 2 local public sector cancer centres over a 1-year period in order to define their epidemiological characteristics and outcomes, and also to assess the uptake of early discharge/outpatient management strategies for these patients.</p><p><b>RESULTS</b>We reviewed 306 FN episodes from 248 patients. Patient characteristics and outcomes were similar between both institutions. Eleven (3.7%) FN episodes were managed as outpatient and none developed complications. Overall 30-day mortality was 6.6%, while the median length of stay (LOS) was 7 days (IQR: 4 to 11 days). The only independent risk factor for mortality was severe sepsis (OR:13.19; 95% CI: 1.98 to 87.7; P = 0.008). Factors independently associated with a longer LOS were vancomycin prescription (coefficient: 0.25; 95% CI: 0.08 to 0.41; P = 0.003), longer duration of intravenous antibiotics (coefficient: 0.08; 95% CI: 0.06 to 0.10; P <0.001), and prior review by an infectious diseases physician (coefficient: 0.16; 95% CI: 0.01 to 0.31; P = 0.034).</p><p><b>CONCLUSION</b>This audit demonstrated that mortality from FN in our 2 cancer centres is low and comparable to international institutions. It also demonstrates that outpatient management of FN is safe in selected patients, and can be further expanded for right-siting of resources.</p>

Nasal metastases from renal cell carcinoma are associated with Memorial Sloan-Kettering Cancer Center poor-prognosis classification / 癌症

Unusual sites of metastases are recognized in patients with renal cell carcinoma (RCC). However, the prognostic implications of these sites are not well understood. We used the Memorial Sloan-Kettering Cancer Center (MSKCC) risk classification for metastatic RCC to evaluate 912 consecutive patients with RCC managed at the Singapore General Hospital between 1990 and 2009. Among these patients, 301 had metastases either at diagnosis or during the course of illness. Nasal metastases, all arising from clear cell RCC, were identified histologically in 4 patients (1.3% of those with metastasis). All 4 patients were classified as MSKCC poor prognosis by current risk criteria. Nasal metastases were significantly associated with lung and bone metastases. The frequency of nasal metastases in patients with metastatic RCC is about 1%, occurring predominantly in patients with clear cell RCC. Nasal metastases are associated with poor prognosis as estimated by the MSKCC risk classification, with attendant implications for selection of targeted therapy, and are usually associated with multi-organ dissemination, including concurrent lung and bone involvement.

Stage T1N0M0 renal cell carcinoma: the prognosis in Asian patients / 癌症

The prognostic features of T1N0M0 renal cell carcinoma (RCC) in Asian patients have not been well explored in large sample studies. In this study, we retrospectively analyzed the records of 713 patients undergoing nephrectomy for T1N0M0 RCC between 1991 and 2009 in three Asian hospitals. Univariate and multivariate analysis were performed to identify the independent predictive factors for T1N0M0 RCC prognosis among a series of clinicopathological parameters, including age, gender, tumor size, Fuhrman grade, and histological classification. Our results showed that 388 of 713 patients had tumors 4.0 cm or smaller (stage T1a) and 325 of 713 patients had tumors 4.0-7.0 cm in size (stage T1b). Five-year cancer-specific survival (CSS) and recurrence-free survival (RFS) rates for this group of patients were 96.0% and 93.5%, respectively. The patients with T1b RCC had a significantly lower 5-year CSS and RFS rates than did those with T1a RCC (CSS, 93.1% vs. 98.6%, P = 0.026; RFS, 90.0% vs. 96.5%, P < 0.001). Patients with low grade (grades I-II) tumors had a higher 5-year CSS (97.8% vs. 91.2%, P = 0.001) and RFS (95.5% vs. 85.5%, P < 0.001) rate than did those with high grade (grades I-II) tumors. More interestingly, when stratifying patients to T1a and T1b groups, the role of grade in distinguishing prognosis could be only observed in patients with T1b disease. Cox regression showed tumor size and Fuhrman grade were significant in predicting CSS and RFS. Our study suggests that the prognosis of patients with T1N0M0 RCC is excellent, and these results are comparable to previously reported studies in Western patients. Furthermore, our data indicates that patients with T1b disease and high Fuhrman grade have high risk of tumor recurrence and death, thus requiring more frequent follow-up.

A unique pair of monozygotic twins with concordant clear cell renal cell carcinoma: a case report

<p><b>INTRODUCTION</b>Genetic predisposition to clear cell renal cell carcinoma (ccRCC) has been linked to disorders such as von Hippel-Lindau (VHL) syndrome. While twin research is a classic approach for elucidating genetic and environmental contributions to disease, no monozygotic twin-pair concordant for ccRCC in the absence of VHL syndrome has been previously reported in the literature or in major twin registries.</p><p><b>CLINICAL PICTURE</b>We describe a unique monozygotic twin-pair concordant for ccRCC, with discordant but early ages of onset of 25 and 38 respectively. Cytogenetic studies and direct sequencing for VHL gene mutations in the second twin proved unremarkable.</p><p><b>CONCLUSIONS</b>This is the fi rst reported case of monozygotic twins concordant for ccRCC in the absence of VHL gene mutation. The early yet discordant, age of onset of disease in both twins suggests both genetic and environmental contributions to ccRCC.</p>

The Tao of bao: a randomised controlled trial examining the effect of steamed bun consumption on night-call inpatient course and mortality

<p><b>BACKGROUND</b>Medical superstitions remain prevalent in today's stressful and technology driven healthcare environment. These irrational beliefs commonly involve night calls, which are periods of volatile workload. In Singapore and Hong Kong, it is commonly held that consumption of steamed buns ("bao") by on-call physicians is associated with increased patient admissions and mortality, due to a homonymous interpretation of the word "bao" in dialect.</p><p><b>MATERIALS AND METHODS</b>A prospective unblinded randomised controlled trial with a permuted block randomisation design was performed on weekdays over 6 weeks. Steamed buns or control food were offered to the internal medicine night-call team of a tertiary-care hospital on a nightly basis. Information on admissions and mortality was collected from the hospital electronic database. Data on sleep patterns and shift duration were obtained by interview.</p><p><b>RESULTS</b>There were no significant differences in the median number of hours slept on days on "bao" administration versus "control" intervention (2 +/- median absolute variation of 1.5 h vs 2 +/- 1.5 h, P = 0.30) or in the number of hours spent in the hospital (30.8 +/- 1.9 h vs 30.5 +/- 2.2 h, P = 0.09). There were no significant differences in the median number of general ward admissions per night (n = 73 +/- 6 versus 71 +/- 7 admissions, P = 0.35), monitored care unit admissions (4 +/- 1.5 vs 4 +/- 1.5 admissions, P = 0.65) or inpatient mortality (2 +/- 1.5 vs 2 +/- 1.5 deaths per night, P = 0.47).</p><p><b>CONCLUSION</b>The consumption of steamed buns ("bao") has no effect on inpatient admissions, mortality, or sleep duration on call. Regardless, our results indicate that the night call in Singapore remains a challenge in terms of workload and shift duration.</p>