Every minute counts: A comparison of thawing times and haemostatic quality of plasma thawed at 37°C and 45°C using four different methods.

BACKGROUND: Having faster plasma thawing devices could be beneficial for transfusion services, as it may improve the rapid availability of thawed plasma for bleeding patients, and it might remove the need to have extended pre-thawed plasma: thus, reducing unnecessary plasma wastage. STUDY DESIGN AND METHODS: The aims of this study were to assess (a) the thawing times and (b) in vitro haemostatic quality of thawed plasma using Barkey Plasmatherm V (PTV) at 37 and 45°C versus Barkey Plasmatherm Classic (PTC) at 37 and 45°C, Sarstedt Sahara-III Maxitherm (SS-III) at 37°C and Helmer Scientific Thermogenesis Thermoline (TT) at 37°C. Haemostatic quality was assessed using LG-Octaplas at three different time points: baseline (5 min), 24 and 120 h after thawing. RESULTS: The thawing time (SD) of 2 and 4 units was significantly different between different thawers. PTV at 45°C was the fastest method for both 2 and 4 units (7.06 min [0.68], 9.6 min [0.87], respectively). SS-III at 37°C being the slowest method (24.69 min [2.09] and 27.18 min [4.4], respectively) (p = < 0.05). Baseline measurements for all assays showed no significant difference in the prothrombin time, fibrinogen, FII, FV, protein C activity or free protein S antigen between all methods tested. However, at baseline PTV (both 37°C and 45°C) had significantly higher levels of FVII, FVIII and FXI and shortened activated partial thromboplastin time. DISCUSSION: PTV was the quickest method at thawing plasma at both 37 and at 45°C. The haemostatic quality of plasma thawed at 45 versus 37°C was not impaired. Thawing frozen plasma at 45°C should be considered.

Deletion of Cdh16 Ksp-cadherin leads to a developmental delay in the ability to maximally concentrate urine in mouse.

Ksp-cadherin (cadherin-16) is an atypical member of the cadherin superfamily of cell adhesion molecules that is ubiquitously expressed on the basolateral membrane of epithelial cells lining the nephron and the collecting system of the mammalian kidney. The principal aim of the present study was to determine if Ksp-cadherin played a critical role in the development and maintenance of the adult mammalian kidney by generating and evaluating a mouse line deficient in Ksp-cadherin. Ksp-null mutant animals were viable and fertile, and kidneys from both neonates and adults showed no evidence of structural abnormalities. Immunolocalization and Western blot analyses of Na+-K+-ATPase and E-cadherin indicated that Ksp-cadherin is not essential for either the genesis or maintenance of the polarized tubular epithelial phenotype. Moreover, E-cadherin expression was not altered to compensate for Ksp-cadherin loss. Plasma electrolytes, total CO2, blood urea nitrogen, and creatinine levels were also unaffected by Ksp-cadherin deficiency. However, a subtle but significant developmental delay in the ability to maximally concentrate urine was detected in Ksp-null mice. Expression analysis of the principal proteins involved in the generation of the corticomedullary osmotic gradient and the resultant movement of water identified misexpression of aquaporin-2 in the inner medullary collecting duct as the possible cause for the inability of young adult Ksp-cadherin-deficient animals to maximally concentrate their urine. In conclusion, Ksp-cadherin is not required for normal kidney development, but its absence leads to a developmental delay in maximal urinary concentrating ability.NEW & NOTEWORTHY Ksp-cadherin (cadherin-16) is an atypical member of the cadherin superfamily of cell adhesion molecules that is ubiquitously expressed on the basolateral membrane of epithelial cells lining the nephron and the collecting system. Using knockout mice, we found that Ksp-cadherin is in fact not required for kidney development despite its high and specific expression along the nephron. However, its absence leads to a developmental delay in maximal urinary concentrating ability.

A systematic review of risk assessment tools for contaminated sites - Current perspectives and future prospects.

Health and safety hazards associated with the redevelopment of contaminated sites can be complex and pose considerable risks. A systematic literature review was conducted on risk assessment tools for contaminated sites. These tools have been identified from searching through leading academic databases and other professional sources. For each of the identified tools the relevant risk assessment stages, harm type, hazard category, receptor type and pathways are reported. Findings reveal that despite growing interest in the development of risk assessment tools, there are persistent knowledge gaps identified in this study, which serve as a basis for future research direction to where more advanced practical tools could be invented. For instance, it is evidenced there is a shortfall in practical tools available to contaminated site assessors conducting investigations at the preliminary risk assessment stage. Addressing this opening can benefit the planning process, coordinated between relevant stakeholders and, moreover, reduce uncertainty in the decision-making of contaminated site developers.

Monogenic mimics of Behçet's disease in the young.

OBJECTIVES: Monogenic autoinflammatory disorders (AID) and primary immunodeficiencies can present early in life with features that may be mistaken for Behçet's disease (BD). We aimed to retrospectively describe the clinical and laboratory features of 11 paediatric cases referred for suspected BD who turned out to have an alternative, monogenic disease mimicking BD. METHODS: Retrospective, paediatric BD specialist multicentre case series. Next generation sequencing (NGS) or conventional candidate gene screening approaches were utilized, facilitated in some cases by functional assays. RESULTS: Eleven children referred with suspected BD underwent genetic screening because of atypical BD features, and/or presentation before age 5 years. Eight patients (73%) were Caucasian, two were Pakistani and one was Turkish; 55% were female. A positive family history of BD was reported in 54% cases. The median age of disease onset was 0.6 (range 0.2-2.3) years. All had systemic inflammation and oral ulceration; 5/11 had genital ulceration; 3/11 had ocular involvement; and 9/11 had cutaneous manifestations. Nine/11 had known disease-causing genetic mutations in: TNFAIP3 (n = 2), WDR1 (n = 2), NCF1, AP1S3, LYN, MEFV and GLA. The remaining two cases each had novel variants in STAT1 and TNFRSF1A. CONCLUSION: Rare monogenic diseases can mimic BD, particularly when presenting early in life. These observations are now informing a strategy to explore screening for genetic mimics of BD in a UK cohort of children and adults to better understand the proportion of UK BD patients who may in fact have an underlying monogenetic diagnosis.

A systematic review of outcomes after salvage abdominoperineal resection for persistent or recurrent anal squamous cell cancer.

AIM: Up to 30% of patients with squamous cell cancer of the anus (SCCA) will require a salvage abdominoperineal resection (APR) for either persistent or recurrent disease. The objective of this study was to assess cancer-related outcomes in patients with (i) persistent or (ii) recurrent SCCA. METHOD: Embase and MEDLINE were searched. Publications were included if they assessed overall survival (OS), disease-free survival (DFS) and locoregional recurrence or metastatic disease after salvage APR for persistent or recurrent SCCA. RESULTS: A total of 28 retrospective case series (study size ranged from nine to 111) met our inclusion criteria. The median time to salvage APR was 2.6 months [interquartile range (IQR) 2.6-5.0 months, six studies] for persistent disease and 27.6 months (IQR 15.0-32.7 months, five studies) for recurrent disease. The median 5-year OS from the time of salvage APR was 45.0% (IQR 32.0%-52.3%, 10 studies) for persistent disease and 51.0% (IQR 36.0%-60.9%, 11 studies) for recurrent disease. The median 5-year DFS following salvage APR was 44.0% (IQR 29.5%-53.0%, 10 studies) for all patients. Following salvage APR, the median locoregional recurrence rate was 23.5% (IQR 15.8%- 46.9%, 19 studies) and 9.0% (IQR 6.4%-13.3%, 16 studies) of patients developed metastatic disease after salvage APR. CONCLUSION: Our review characterizes the best evidence for outcomes following salvage APR for patients with persistent or recurrent SCCA. The evidence is limited by the quality of included studies, as many were single centre case series.

Development of small particle speciation for nuclear forensics by soft X-ray scanning transmission spectromicroscopy.

Synchrotron radiation spectromicroscopy provides a combination of submicron spatial resolution and chemical sensitivity that is well-suited to analysis of heterogeneous nuclear materials. The chemical and physical characteristics determined by scanning transmission X-ray microscopy (STXM) are complementary to information obtained from standard radiochemical analysis methods. In addition, microscopic quantities of radioactive material can be characterized rapidly by STXM with minimal sample handling and intrusion, especially in the case of particulate materials. The STXM can accommodate a diverse range of samples including wet materials, complex mixtures, and small quantities of material contained in a larger matrix. In these cases, the inventory of species present in a sample is likely to carry information on its process history; STXM has the demonstrated capability to identify contaminants and sample matrices. Operating in the soft X-ray regime provides particular sensitivity to the chemical state of specimens containing low-Z materials, via the K-edges of light elements. Here, recent developments in forensics-themed spectromicroscopy, sample preparation, and data acquisition methods at the Molecular Environmental Science Beamline 11.0.2 of the Advanced Light Source are described. Results from several initial studies are presented, demonstrating the capability to identify the distribution of the species present in heterogeneous uranium-bearing materials. Future opportunities for STXM forensic studies and potential methodology development are discussed.

National Comparative Audit of Blood Transfusion: report on the 2014 audit of patient information and consent.

OBJECTIVES: The aim of this study was to assess current practices around obtaining consent for blood transfusion and provision of patient information in hospitals across the UK and identify areas for improvement. BACKGROUND: Recommendations from the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) (2011) state that valid consent should be obtained for blood transfusion and documented in clinical records. A standardised source of information should be available to patients. Practices in relation to this have historically been inconsistent. METHODS: The consent process was studied in hospitals across the UK over a 3-month period in 2014 by means of an audit of case notes and simultaneous surveys of patients and staff. RESULTS: In total, 2784 transfusion episodes were reviewed across 164 hospital sites. 85% of sites had a policy on consent for transfusion. Consent was documented in 43% of case notes. 68% of patients recalled being given information on benefits of transfusion, 38% on risks and 8% on alternatives and 28% reported receiving an information leaflet. In total, 85% of staff stated they had explained the reason for transfusion, but only 65% had documented this. 41% of staff had received training specifically on transfusion consent in the last 2 years. CONCLUSIONS: There is a need to improve clinical practice in obtaining valid consent for transfusion in line with existing national guidelines and local Trust policies, with emphasis on documentation within clinical records. Provision of patient information is an area particularly highlighted for action, and transfusion training for clinicians should be strengthened.

Do Contemporary Randomized Controlled Trials Meet ESMO Thresholds for Meaningful Clinical Benefit?

Background: The European Society for Medical Oncology (ESMO) recently released a magnitude of clinical benefit scale (ESMO-MCBS) for systemic therapies for solid cancers. Here, we evaluate contemporary randomized controlled trials (RCTs) against the proposed ESMO thresholds for meaningful clinical benefit. Methods: RCTs evaluating systemic therapy for breast cancer, nonsmall cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic cancer published 2011-2015 were reviewed. Data were abstracted regarding trial characteristics and outcomes, and these were applied to the ESMO-MCBS. We also determined whether RCTs were designed to detect an effect that would meet clinical benefit as defined by the ESMO-MCBS. Results: About 277 eligible RCTs were included (40% breast, 31% NSCLC, 22% CRC, 6% pancreas). Median sample size was 532 and 83% were funded by industry. Among all 277 RCTs, the experimental therapy was statistically superior to the control arm in 138 (50%) trials: results of only 31% (43/138) of these trials met the ESMO-MCBS clinical benefit threshold. RCTs with curative intent were more likely to meet clinically meaningful thresholds than those with palliative intent [61% (19/31) versus 22% (24/107), P < 0.001]. Among the 226 RCTs for which the ESMO-MCBS could be applied, 31% (70/226) were designed to detect an effect size that could meet ESMO-MCBS thresholds. Conclusion: Less than one-third of contemporary RCTs with statistically significant results meet ESMO thresholds for meaningful clinical benefit, and this represents only 15% of all published trials. Investigators, funding agencies, regulatory agencies, and industry should adopt more stringent thresholds for meaningful benefit in the design of future RCTs.

Population-based study to re-evaluate optimal lymph node yield in colonic cancer.

BACKGROUND: It is well established that lymph node (LN) yield in colonic cancer resection has prognostic significance, although optimal numbers are not clear. Here, LN thresholds associated with both LN positivity and survival were evaluated in a single population-based data set. METHODS: Treatment records were linked to the Ontario Cancer Registry to identify a 25 per cent random sample of all patients with stage II/III colonic cancer between 2002 and 2008. Multivariable regression and Cox models evaluated factors associated with LN positivity and cancer-specific survival (CSS) respectively. Optimal thresholds were obtained using sequential regression analysis. RESULTS: On adjusted analysis of 5508 eligible patients, younger age (P < 0·001), left-sided tumours (P = 0·003), higher T category (P < 0·001) and greater LN yield (relative risk 0·89, 95 per cent c.i. 0·81 to 0·97; P = 0·007) were associated with a greater likelihood of LN positivity. Regression analyses with multiple thresholds suggested no substantial increase in LN positivity beyond 12-14 LNs. Cox analysis of stage II disease showed that lower LN yield was associated with a significant increase in the risk of death from cancer (CSS hazard ratio range 1·55-1·74; P < 0·001) compared with a greater LN yield, with no significant survival benefit beyond a yield of 20 LNs. Similarly, for stage III disease, a lower LN yield was associated with an increase in the risk of death from cancer (CSS hazard ratio range 1·49-2·20; P < 0·001) versus a large LN yield. In stage III disease, there was no observed LN threshold for survival benefit in the data set. CONCLUSION: There is incongruity in the optimal LN evaluation for colonic cancer. Although the historically stated threshold of 12 LNs may ensure accurate staging in colonic cancer, thresholds for optimal survival are associated with far greater yields.

Is there a sex effect in colon cancer? Disease characteristics, management, and outcomes in routine clinical practice.

INTRODUCTION: The incidence of colon cancer varies by sex. Whether women and men show differences in extent of disease, treatment, and outcomes is not well described. We used a large population-based cohort to evaluate sex differences in colon cancer. METHODS: Using the Ontario Cancer Registry, all cases of colon cancer treated with surgery in Ontario during 2002-2008 were identified. Electronic records of treatment identified use of surgery and adjuvant chemotherapy. Pathology reports for a random 25% sample of all cases were obtained, and disease characteristics, treatment, and outcomes in women and men were compared. A Cox proportional hazards model was used to identify factors associated with overall (os) and cancer-specific survival (css). RESULTS: The study population included 7249 patients who underwent resection of colon cancer; 49% (n = 3556) were women. Stage of disease and histologic grade did not vary by sex. Compared with men, women were more likely to have right-sided disease (55% vs. 44%, p ≤ 0.001). Surgical procedure and lymph node yield did not differ by sex. Adjuvant chemotherapy was delivered to 18% of patients with stage ii and 64% of patients with stage iii disease; when adjusted for patient- and disease-related factors, use of adjuvant chemotherapy was similar for women and men [relative risk: 0.99; 95% confidence interval (ci): 0.94 to 1.03]. Adjusted analyses demonstrated that os [hazard ratio (hr): 0.80; 95% ci: 0.75 to 0.86] and css (hr: 0.82; 95% ci: 0.76 to 0.90) were superior for women compared with men. CONCLUSIONS: Long-term survival after colon cancer is significantly better for women than for men, which is not explained by any substantial differences in extent of disease or treatment delivered.

Lymph node evaluation for colon cancer in routine clinical practice: a population-based study.

BACKGROUND: Guidelines recommend that 12 or more lymph nodes (lns) be evaluated during surgical resection of colon cancer. Here, we report ln yield and its association with survival in routine practice. METHODS: Electronic records of treatment were linked to the population-based Ontario Cancer Registry to identify all patients with colon cancer treated during 2002-2008. The study population (n = 5508) included a 25% random sample of patients with stage ii or iii disease. Modified Poisson regression was used to identify factors associated with ln yield; Cox models were used to explore the association between ln yield and overall (os) and cancer-specific survival (css). RESULTS: During 2002-2008, median ln yield increased to 17 from 11 nodes (p < 0.001), and the proportion of patients with 12 or more nodes evaluated increased to 86% from 45% (p < 0.001). Lymph node positivity did not change over time (to 53% from 54%, p = 0.357). Greater ln yield was associated with younger age (p < 0.001), less comorbidity (p = 0.004), higher socioeconomic status (p = 0.001), right-sided tumours (p < 0.001), and higher hospital volume (p < 0.001). In adjusted analyses, a ln yield of less than 12 nodes was associated with inferior os and css for stages ii and iii disease [stage ii os hazard ratio (hr): 1.36; 95% confidence interval (ci): 1.19 to 1.56; stage ii css hr: 1.52; 95% ci: 1.26 to 1.83; and stage iii os hr: 1.45; 95% ci: 1.30 to 1.61; stage iii css hr: 1.54; 95% ci: 1.36 to 1.75]. CONCLUSIONS: Despite a temporal increase in ln yield, the proportion of cases with ln positivity has not changed. Lymph node yield is associated with survival in patients with stages ii and iii colon cancer. The association between ln yield and survival is unlikely to be a result of stage migration.

Toward improved goals-of-care documentation in advanced cancer: report on the development of a quality improvement initiative.

BACKGROUND: Documentation of advance care planning for patients with terminal cancer is known to be poor. Here, we describe a quality improvement initiative. METHODS: Patients receiving palliative chemotherapy for metastatic lung, pancreatic, colorectal, and breast cancer during 2010-2015 at the Cancer Centre of Southeastern Ontario were identified from electronic pharmacy records. Clinical notes were reviewed to identify documentation of care plans in the event of acute deterioration. After establishing baseline practice, we sought to improve documentation of goals of care and referral rates to palliative care. Using quality improvement methodology, we developed a guideline, a standardized documentation system, and a process to facilitate early referral to palliative care. RESULTS: During 2010-2015, 456 patients were included in the baseline cohort: 63% with lung cancer, 16% with colorectal cancer, 13% with pancreatic cancer, and 7% with breast cancer. Care goals in the event of an acute illness were documented by medical oncologists in 6% of cases (26 of 456). Of the 456 patients, 47% (n = 214) were seen by palliative care; care goals were documented by palliative care in 48% of the patients seen (103 of 214). With those baseline data in hand, a local practice guideline and process was developed to facilitate the identification of patients for whom advance care planning and early palliative care referral should be considered. A system was also established so that goals-of-care documentation will be supported with a written framework and broadly accessible in the electronic medical record. CONCLUSIONS: Low rates of documentation of advance care planning and referral to palliative care persist and have stimulated a local quality improvement initiative.

Mental health services use by melanoma patients receiving adjuvant interferon: association of pre-treatment mental health care with early discontinuation.

BACKGROUND: Although high-dose interferon (hd-ifn) is the sole approved adjuvant systemic treatment for melanoma in many jurisdictions, it is toxic. We sought to assess the population-level effects of hd-ifn toxicity, particularly neuropsychiatric toxicity, hypothesizing that such toxicity would have the greatest effect on mental health services use in advanced resected melanoma. METHODS: This retrospective population-based registry study considered all melanoma patients receiving adjuvant hd-ifn in Ontario during 2008-2012. Toxicity was investigated through health services use compatible with hd-ifn toxicity (for example, mental health physician billings). Using stage data reported from cancer centres about a subset of patients (stages iib-iiic), a propensity-matched analysis compared such service use in patients who did and did not receive hd-ifn. Associations between early hd-ifn discontinuation and health services use were examined. RESULTS: Of 718 melanoma patients who received hd-ifn, 12% were 65 years of age and older, and 83% had few or no comorbidities. One third of the patients experienced 1 or more toxicity-associated health care utilization events within 1 year of starting hd-ifn. Of 420 utilization events, 364 (87%) were mental health-related, with 54% being family practitioner visits, and 39% being psychiatrist visits. In the propensity-matched analysis, patients receiving hd-ifn were more likely than untreated matched controls to use a mental health service (p = 0.01), with 42% of the control group and 51% of the hd-ifn group using a mental health service in the period spanning the 12 months before to the 24 months after diagnosis. In the multivariable analysis, early drug discontinuation was more likely in the presence of pre-existing mental health issues (odds ratio: 2.0; 95% confidence limits: 1.1, 3.4). CONCLUSIONS: Stage iib-iiic melanoma patients carry a substantial burden of mental health services use whether or not receiving hd-ifn, highlighting an important survivorship issue for these patients. High-dose interferon is associated with more use of mental health services, and pre-treatment use of mental health services is associated with treatment discontinuation. That association should be kept in mind when hd-ifn is being considered.

Research output and the public health burden of cancer: is there any relationship?

PURPOSE: The relative distribution of research output across cancer sites is not well described. Here, we evaluate whether the volume of published research is proportional to the public health burden of individual cancers. We also explore whether research output is proportional to research funding. METHODS: Statistics from the Canadian and American cancer societies were used to identify the top ten causes of cancer death in 2013. All journal articles and clinical trials published in 2013 by Canadian or U.S. authors for those cancers were identified. Total research funding in Canada by cancer site was obtained from the Canadian Cancer Research Alliance. Descriptive statistics and Pearson correlation coefficients were used to describe the relationship between research output, cancer mortality, and research funding. RESULTS: We identified 19,361 publications and 2661 clinical trials. The proportion of publications and clinical trials was substantially lower than the proportion of deaths for lung (41% deaths, 15% publications, 16% clinical trials), colorectal (14%, 7%, 6%), pancreatic (10%, 7%, 5%), and gastroesophageal (7%, 5%, 3%) cancers. Conversely, research output was substantially greater than the proportion of deaths for breast cancer (10% deaths, 29% publications, 30% clinical trials) and prostate cancer (8%, 15%, 17%). We observed a stronger correlation between research output and funding (publications r = 0.894, p < 0.001; clinical trials r = 0.923, p < 0.001) than between research output and cancer mortality (r = 0.363, p = 0.303; r = 0.340, p = 0.337). CONCLUSIONS: Research output is not well correlated with the public health burden of individual cancers, but is correlated with the relative level of research funding.

Eastern Canadian Colorectal Cancer Consensus Conference 2013: emerging therapies in the treatment of pancreatic, rectal, and colorectal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer.

Multiconfigurational nature of 5f orbitals in uranium and plutonium intermetallics.

Uranium and plutonium's 5f electrons are tenuously poised between strongly bonding with ligand spd-states and residing close to the nucleus. The unusual properties of these elements and their compounds (e.g., the six different allotropes of elemental plutonium) are widely believed to depend on the related attributes of f-orbital occupancy and delocalization for which a quantitative measure is lacking. By employing resonant X-ray emission spectroscopy (RXES) and X-ray absorption near-edge structure (XANES) spectroscopy and making comparisons to specific heat measurements, we demonstrate the presence of multiconfigurational f-orbital states in the actinide elements U and Pu and in a wide range of uranium and plutonium intermetallic compounds. These results provide a robust experimental basis for a new framework toward understanding the strongly-correlated behavior of actinide materials.

Comparing effectiveness with efficacy: outcomes of palliative chemotherapy for non-small-cell lung cancer in routine practice.

INTRODUCTION: Randomized controlled trials (rcts) are the "gold standard" for establishing treatment efficacy; however, efficacy does not automatically translate to a comparable level of effectiveness in routine practice. Our objectives were to □ describe outcomes of palliative platinum-doublet chemotherapy (ppdc) in non-small-cell lung cancer (nsclc) in routine practice, in terms of survival and well-being; and□ compare the effectiveness of ppdc in routine practice with its efficacy in rcts. METHODS: Electronic treatment records were linked to the Ontario Cancer Registry to identify patients who underwent ppdc for nsclc at Ontario's regional cancer centres between April 2008 and December 2011. At each visit to the cancer centre, a patient's symptoms are recorded using the Edmonton Symptom Assessment System (esas). Score on the esas "well-being" item was used here as a proxy for quality of life (qol). Survival in the cohort was compared with survival in rcts, adjusting for differences in case mix. Changes in the esas score were measured 2 months after treatment start. The proportion of patients having improved or stable well-being was compared with the proportion having improved or stable qol in relevant rcts. RESULTS: We identified 906 patients with pre-ppdcesas records. Median survival was 31 weeks compared with 28-48 weeks in rcts. After accounting for deaths and cases lost to follow-up, we estimated that, at 2 months, 62% of the cohort had improved or stable well-being compared with 55%-63% who had improved or stable qol in rcts. CONCLUSIONS: The effectiveness of ppdc for nsclc in routine practice in Ontario is consistent with its efficacy in rcts, both in terms of survival and improvement in well-being.

Delivery of perioperative chemotherapy for bladder cancer in routine clinical practice.

BACKGROUND: Few articles have documented regimens and timing of perioperative chemotherapy for bladder cancer in routine practice. Here, we describe practice patterns in the general population of Ontario, Canada. METHODS: In this retrospective cohort study, treatment and physician billing records were linked to the Ontario Cancer Registry to describe use of neoadjuvant (NACT) and adjuvant (ACT) chemotherapy among all patients with muscle-invasive bladder cancer treated with cystectomy in Ontario 1994-2008. Time to initiation of ACT (TTAC) was measured from cystectomy. Multivariate Cox regression was used to identify factors associated with overall (OS) and cancer-specific survival (CSS). RESULTS: Of 2944 patients undergoing cystectomy, 4% (129/2944) and 19% (571/2944) were treated with NACT and ACT, respectively. Five-year OS was 25% [95% confidence interval (CI) 17% to 34%] for NACT, 29% (95% CI 25% to 33%) for ACT cases. Among patients with identifiable drug regimens, cisplatin was used in 82% (253/308) and carboplatin in 14% (43/308). The most common regimens were gemcitabine-cisplatin (54%, 166/308) and methotrexate, vinblastine, doxorubicin, cisplatin (MVAC) (21%, 66/308). Mean TTAC was 10 weeks; 23% of patients had TTAC >12 weeks. TTAC >12 weeks was associated with inferior OS [hazard ratio (HR) 1.28, 95% CI 1.00-1.62] and CSS (HR 1.30, 95% CI 1.00-1.69). In adjusted analyses, OS and CSS were lower among patients treated with carboplatin compared with those treated with cisplatin; OS HR 2.14 (95% CI 1.40-3.29) and CSS HR 2.06 (95% CI 1.26-3.37). CONCLUSIONS: Most patients in the general population receive cisplatin, and this may be associated with superior outcomes to carboplatin. Initiation of ACT beyond 12 weeks is associated with inferior survival. Patients should start ACT as soon as they are medically fit to do so.