A phase 1 study of nivolumab in combination with interferon-gamma for patients with advanced solid tumors.

This phase I, dose-escalation trial evaluates the safety of combining interferon-gamma (IFN-γ) and nivolumab in patients with metastatic solid tumors. Twenty-six patients are treated in four cohorts assessing increasing doses of IFN-γ with nivolumab to evaluate the primary endpoint of safety and determine the recommended phase two dose (RP2D). Most common adverse events are low grade and associated with IFN-γ. Three dose limiting toxicities are reported at the highest dose cohorts. We report only one patient with any immune related adverse event (irAE). No irAEs ≥ grade 3 are observed and no patients require corticosteroids. The maximum tolerated dose of IFN-γ is 75 mcg/m2, however based on a composite of safety, clinical, and correlative factors the RP2D is 50 mcg/m2. Exploratory analyses of efficacy in the phase I cohorts demonstrate one patient with a complete response, and five have achieved stable disease. Pre-planned correlative assessments of circulating immune cells demonstrate intermediate monocytes with increased PD-L1 expression correlating with IFN-γ dose and treatment duration. Interestingly, post-hoc analysis shows that IFN-γ induction increases circulating chemokines and is associated with an observed paucity of irAEs, warranting further evaluation. ClinicalTrials.gov Trial Registration: NCT02614456.

Multi-omics Visualization Platform: An extensible Galaxy plug-in for multi-omics data visualization and exploration.

BACKGROUND: Proteogenomics integrates genomics, transcriptomics, and mass spectrometry (MS)-based proteomics data to identify novel protein sequences arising from gene and transcript sequence variants. Proteogenomic data analysis requires integration of disparate 'omic software tools, as well as customized tools to view and interpret results. The flexible Galaxy platform has proven valuable for proteogenomic data analysis. Here, we describe a novel Multi-omics Visualization Platform (MVP) for organizing, visualizing, and exploring proteogenomic results, adding a critically needed tool for data exploration and interpretation. FINDINGS: MVP is built as an HTML Galaxy plug-in, primarily based on JavaScript. Via the Galaxy API, MVP uses SQLite databases as input-a custom data type (mzSQLite) containing MS-based peptide identification information, a variant annotation table, and a coding sequence table. Users can interactively filter identified peptides based on sequence and data quality metrics, view annotated peptide MS data, and visualize protein-level information, along with genomic coordinates. Peptides that pass the user-defined thresholds can be sent back to Galaxy via the API for further analysis; processed data and visualizations can also be saved and shared. MVP leverages the Integrated Genomics Viewer JavaScript framework, enabling interactive visualization of peptides and corresponding transcript and genomic coding information within the MVP interface. CONCLUSIONS: MVP provides a powerful, extensible platform for automated, interactive visualization of proteogenomic results within the Galaxy environment, adding a unique and critically needed tool for empowering exploration and interpretation of results. The platform is extensible, providing a basis for further development of new functionalities for proteogenomic data visualization.

Sporadic Angiomyolipomas Growth Kinetics While on Everolimus: Results of a Phase II Trial.

PURPOSE: Everolimus decreases tumor volume of renal angiomyolipomas in patients with tuberous sclerosis. No prospective data are available regarding the effect of everolimus on the growth kinetics in patients with sporadic angiomyolipomas. We sought to determine the safety and efficacy of everolimus in the volumetric reduction of sporadic angiomyolipomas. MATERIALS AND METHODS: This multi-institutional, prospective, phase II trial, enrolled patients with 3 cm or larger sporadic angiomyolipomas who were candidates for surgical resection or percutaneous angioembolization. Patients received 10 mg everolimus daily for 4 planned 28-day cycles. Response was defined as a 25% or greater volumetric reduction of patient angiomyolipoma. Baseline, 4, 6 and 12-month volumetric analyses were performed using magnetic resonance imaging. Everolimus was discontinued in those with less than 25% volumetric reduction after 4 cycles. Those with 25% or greater volumetric reduction received 2 additional cycles. The primary outcomes were the efficacy of everolimus in the volumetric reduction of angiomyolipomas by 25% or more, and the safety and tolerability of everolimus. RESULTS: Overall 20 patients were enrolled at 5 centers. Of these patients 11 (55%) completed 4 cycles and 7 (35%) completed 6 cycles. Efficacy was demonstrated, with 10 of 18 (55.6%) patients exhibiting a 25% or greater reduction in tumor volume at 4 months (median 58.5%) and 10 of 14 (71.4%) patients exhibiting a 25% or greater reduction in tumor volume at 6 months (median 58.2%). Four (20%) patients were withdrawn due to protocol defined toxicities and 8 (40%) self-withdrew from the study due to side effects. CONCLUSIONS: Everolimus was effective in causing volumetric reduction of angiomyolipomas by 25% or greater in most patients but was associated with a high rate of treatment discontinuation.

External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial.

BACKGROUND: Whole breast irradiation delivered once per day over 3-5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. METHODS: We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5-8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov, NCT00282035. FINDINGS: Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3-9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9-4·0) in the APBI group and 2·8% (1·8-3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84-1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p<0·0001). Late radiation toxicity (grade ≥2, later than 3 months) was more common in patients treated with APBI (346 [32%] of 1070 patients) than whole breast irradiation (142 [13%] of 1065 patients; p<0·0001). Adverse cosmesis (defined as fair or poor) was more common in patients treated with APBI than in those treated by whole breast irradiation at 3 years (absolute difference, 11·3%, 95% CI 7·5-15·0), 5 years (16·5%, 12·5-20·4), and 7 years (17·7%, 12·9-22·3). INTERPRETATION: External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. FUNDING: Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

An Accessible Proteogenomics Informatics Resource for Cancer Researchers.

Proteogenomics has emerged as a valuable approach in cancer research, which integrates genomic and transcriptomic data with mass spectrometry-based proteomics data to directly identify expressed, variant protein sequences that may have functional roles in cancer. This approach is computationally intensive, requiring integration of disparate software tools into sophisticated workflows, challenging its adoption by nonexpert, bench scientists. To address this need, we have developed an extensible, Galaxy-based resource aimed at providing more researchers access to, and training in, proteogenomic informatics. Our resource brings together software from several leading research groups to address two foundational aspects of proteogenomics: (i) generation of customized, annotated protein sequence databases from RNA-Seq data; and (ii) accurate matching of tandem mass spectrometry data to putative variants, followed by filtering to confirm their novelty. Directions for accessing software tools and workflows, along with instructional documentation, can be found at z.umn.edu/canresgithub. Cancer Res; 77(21); e43-46. ©2017 AACR.

Experience with curative radiotherapy for cervix cancer in the Bahamas for 2006-2016.

BACKGROUND: Cervix cancer is a significant health problem. As access to quality care in Small Island Developing States improves, and cancer centers become established, providers of care can summarize local experience to benchmark system quality and look for ways to further improve value. METHODS: This is a retrospective study of all cases of cervix cancer managed 2006-2016 at The Cancer Centre Bahamas, in conjunction with Princess Margaret Hospital, Nassau, affiliated with The University of West Indies. Seventy-two women received curative radiotherapy or chemoradiotherapy. Herein are reported presenting characteristics, treatments, waiting and overall treatment times, plus outcomes of recurrence, survival, and adverse events. RESULTS: For 68 newly diagnosed cases, median waiting time (diagnosis to commencing treatment) was 110 days. It was 90 days for those 47 cases who had no prior surgery or neoadjuvant chemotherapy. Overall, 99% of intended external radiotherapy fractions, 74% of brachytherapy sessions, and 79% of concurrent weekly chemotherapy were administered. For all 72 cases, median overall treatment time was 63 days; and for the 47 case sub-group, it was 78 days during 2006-2010 and 65 days during 2011-2016 (p = 0.005), so improving over calendar time. Four cases experienced grade 3-4 toxicities. Twelve had urological complications from disease or treatment. Five cases experienced local failure; eight experienced distant failure. Newly diagnosed stage 2B (26/72) had a 2-year survival of 71%. CONCLUSION: This report demonstrates the impact of providing curative radiation-based treatments for cervical cancer in a small state. It suggests ways to further improve operations and justifies additional research.

Outcomes of treatment in men with prostate cancer at the cancer centre Bahamas.

PURPOSE: This is a first report from The Bahamas of management and long-term outcomes in men with non-metastatic prostate cancer treated with radiotherapy, with or without androgen deprivation therapy, from 2004 to 2016. METHODS: Patients were characterized by baseline factors, stratified by risk groups using tumor stage (clinical T-stage), prostate-specific antigen (PSA) test result and Gleason grade, and sorted by treatment combinations (by radiation volume and use of androgen deprivation). RESULTS: Overall, 205/216 men were Afro-Caribbean. Median age was 66. There were 18 low-, 77 intermediate-, and 121 high-risk patients, treated with prostate-only versus pelvis plus prostate radiotherapy, many receiving 2 years of androgen suppression. Time to commence radiation was about 6 months from initial diagnosis. In those not relapsing, global PSA nadir was reached in 4 years and was under 1.0, reduced from a mean at baseline of 31. At 10 years, disease-free experience (32 relapses) was 68% and overall survival was 87%, although only 2/12 deaths were related to prostate cancer. This experience compares favorably with recently published outcomes from other countries using very similar treatments. CONCLUSIONS: This study establishes benchmark statistics from diagnosis to long-term follow-up. Outcomes in Bahamian men are consistent with expectations from risk-stratified guidelines followed in developed countries.

Consistency of Organ Geometries during Prostate Radiotherapy with Two Different Bladder and Bowel Regimens.

BACKGROUND: The majority of Ontario cancer centres incorporate bladder and bowel preparation protocols for the treatment of prostate cancer with radical radiotherapy. Differing methods are used to achieve a full bladder and empty rectum for planning and treatment. We compared the effects of two different bladder and bowel preparation regimens on bladder, rectum, and prostate +/- seminal vesicle geometries through a course of radiotherapy. An optimal preparation would achieve reliable spatial arrangements and a high therapeutic ratio. METHODS: This prospective longitudinal study involved 59 prostate cancer patients treated with radical radiotherapy, of which half followed cohort 1 (laxative cohort) and the other cohort 2 (consistent timing cohort) bladder and bowel preparation regimen. Participants were asked to maintain an empty rectum for both planning and daily treatment appointments in cohort 1 through a fleet enema the morning of the planning appointment, and intake milk of magnesium during daily treatments. No specific bowel preparation was provided to cohort 2 patients. Instead, their appointment times were aligned with their natural bowel habits. This information was collected through a prescreening tool before treatment booking. All cohort 1 and 2 participants were asked to drink 250 mL of water 1 hour before planning and daily treatment appointments. Cohort 2 participants who identified no pre-existing urinary conditions were also asked to drink 2 L of water within 24 hours before the planning session and to continue this during treatment trajectory unless unable to do so because of treatment-induced bladder toxicities later in the treatment. A total of 1,335 structures (bladder, rectum +/- gas, and prostate +/- seminal vesicles) were contoured on the cone beam computerized tomography scans by three radiotherapists. A stringent quality assurance process was performed to assure quality and consistency of contours. Organ volumes were measured and evaluated for consistency over time from planning to completion of radiotherapy. Data analysis included the Fischer exact test and mixed effect modelling for total and subvolumes for bladder, rectum, rectal gas, and prostate +/- seminal vesicles. RESULTS: Baseline total volumes for bladder ranged from 132 mL to 501 mL with means of 325 mL and 315 mL in cohorts 1 and 2, respectively. Bladder volume declined 3.6 mL per fraction and 2.4 mL per fraction in cohorts 1 and 2, respectively. The volume of the bladder structure inside the planning target volume (PTV) on simulation showed no difference by cohort (P = .095) but there was an effect of time (linear P < .0005). Baseline total volumes for rectum ranged from 19.2 mL to 106.3 mL with means of 52.0 mL and 54.7 mL in cohorts 1 and 2, respectively. The volume of the rectum inside the PTV on simulation showed no difference by cohort (P = .12) or time (P = .30) during the treatment course. Volume of gas in the rectum did not vary by cohort (P = .6) or time (P = .08). Baseline total volumes for the clinical prostate +/- seminal vesicles target ranged from 37.1 mL to 167.5 mL with means of 76.2 mL and 66.0 mL in cohorts 1 and 2, respectively. The clinical target decreased by 3% in total volume during the course of radiotherapy in both cohorts, with similar rates of the target falling outside the planned PTV structure. CONCLUSIONS: No significant difference was found between cohorts for rectal volume, gas volume, target coverage, and rectal and bladder volumes in the PTV. Hence, patients should be offered a choice between cohort 1 and 2 bowel preparation regimens to allow for patient preference customization. Cohort 2 bladder preparation regimen was shown to be superior for consistency with slightly larger volume over time.

Closing the quality loop: facilitating improvement in oncology practice through timely access to clinical performance indicators.

PURPOSE: Health care organizations and professionals are being called on to develop clear and transparent measures of quality and to demonstrate the application of the data to performance improvement at the system and provider levels. MATERIALS AND METHODS: Cancer Care Ontario (CCO) initiated a pathology reporting project aimed at improving the quality of cancer pathology by standardizing the content, format, and transmission of reports to a central registry and enabling the information to be available for planning, quality measurement, and quality improvement. This population-based quality-improvement project involved more than 400 Ontario pathologists and more than 100 hospitals. Clinically relevant quality indicators that used the newly available data were developed and shared. Synoptic pathology data were electronically captured at the point of report development and used to automate the timely generation of clinical performance indicators that support quality improvement in surgical oncology. These reports provided comparison data at the organizational, regional, and population levels. RESULTS: Monthly quality indicator reports are generated and distributed to each cancer center and are used to generate dialogue at the professional, organizational, and regional levels regarding evidence-informed quality-improvement opportunities. Since the launch of the project, colorectal lymph node retrieval rates have increased from 76% to 87%, and pT2 prostatectomy margin positivity rates have decreased from 37% to 21%. CONCLUSION: High-quality, complete cancer pathology reports are important not only for contemporary oncological practice, but also for secondary users of pathology information including tumor registries, health planners, epidemiologists, and others involved in quality-improvement activities and research.

Standardized synoptic cancer pathology reports - so what and who cares? A population-based satisfaction survey of 970 pathologists, surgeons, and oncologists.

CONTEXT: Cancer Care Ontario implemented synoptic pathology reporting across Ontario, impacting the practice of pathologists, surgeons, and medical and radiation oncologists. The benefits of standardized synoptic pathology reporting include enhanced completeness and improved consistency in comparison with narrative reports, with reported challenges including increased workload and report turnaround time. OBJECTIVE: To determine the impact of synoptic pathology reporting on physician satisfaction specific to practice and process. DESIGN: A descriptive, cross-sectional design was utilized involving 970 clinicians across 27 hospitals. An 11-item survey was developed to obtain information regarding timeliness, completeness, clarity, and usability. Open-ended questions were also employed to obtain qualitative comments. RESULTS: A 51% response rate was obtained, with descriptive statistics reporting that physicians perceive synoptic reports as significantly better than narrative reports. Correlation analysis revealed a moderately strong, positive relationship between respondents' perceptions of overall satisfaction with the level of information provided and perceptions of completeness for clinical decision making (r = 0.750, P < .001) and ease of finding information for clinical decision making (r = 0.663, P < .001). Dependent t tests showed a statistically significant difference in the satisfaction scores of pathologists and oncologists (t169 = 3.044, P = .003). Qualitative comments revealed technology-related issues as the most frequently cited factor impacting timeliness of report completion. CONCLUSION: This study provides evidence of strong physician satisfaction with synoptic cancer pathology reporting as a clinical decision support tool in the diagnosis, prognosis, and treatment of cancer patients.

A two-step database search method improves sensitivity in peptide sequence matches for metaproteomics and proteogenomics studies.

Large databases (>10(6) sequences) used in metaproteomic and proteogenomic studies present challenges in matching peptide sequences to MS/MS data using database-search programs. Most notably, strict filtering to avoid false-positive matches leads to more false negatives, thus constraining the number of peptide matches. To address this challenge, we developed a two-step method wherein matches derived from a primary search against a large database were used to create a smaller subset database. The second search was performed against a target-decoy version of this subset database merged with a host database. High confidence peptide sequence matches were then used to infer protein identities. Applying our two-step method for both metaproteomic and proteogenomic analysis resulted in twice the number of high confidence peptide sequence matches in each case, as compared to the conventional one-step method. The two-step method captured almost all of the same peptides matched by the one-step method, with a majority of the additional matches being false negatives from the one-step method. Furthermore, the two-step method improved results regardless of the database search program used. Our results show that our two-step method maximizes the peptide matching sensitivity for applications requiring large databases, especially valuable for proteogenomics and metaproteomics studies.

Dataset for reporting of prostate carcinoma in radical prostatectomy specimens: recommendations from the International Collaboration on Cancer Reporting.

This project was designed to harmonise the Royal College of Pathologists, College of American Pathologists and Royal College of Pathologists of Australasia datasets, checklists and structured reporting protocols for examination of radical prostatectomy specimens, with the aim of producing a common, internationally agreed, evidence-based dataset for prostate cancer reporting. The International Collaboration on Cancer Reporting prostate cancer expert review panel analysed the three existing datasets, identifying concordant items and classified these data elements as 'required' (mandatory) or 'recommended' (non-mandatory), on the basis of the published literature up to August 2011. Required elements were defined as those that have agreed evidentiary support at NHMRC level III-2 or above. Consensus response values were formulated for each item. Twelve concordant pathology data elements were identified, and, on review, all but one were included as required elements for tumour staging, grading, or prediction of prognosis. There was minor discordance between the three existing datasets for another eight items, with two of these being added to the required data set. Another 11 elements with a lesser level of evidentiary support were included in the recommended dataset. This process was found to be an efficient method for producing an evidence-based dataset for prostate cancer. Such internationally agreed datasets should facilitate meaningful comparison of benchmarking data, epidemiological studies, and clinical trials.

Deep metaproteomic analysis of human salivary supernatant.

The human salivary proteome is extremely complex, including proteins from salivary glands, serum, and oral microbes. Much has been learned about the host component, but little is known about the microbial component. Here we report a metaproteomic analysis of salivary supernatant pooled from six healthy subjects. For deep interrogation of the salivary proteome, we combined protein dynamic range compression (DRC), multidimensional peptide fractionation, and high-mass accuracy MS/MS with a novel two-step peptide identification method using a database of human proteins plus those translated from oral microbe genomes. Peptides were identified from 124 microbial species as well as uncultured phylotypes such as TM7. Streptococcus, Rothia, Actinomyces, Prevotella, Neisseria, Veilonella, Lactobacillus, Selenomonas, Pseudomonas, Staphylococcus, and Campylobacter were abundant among the 65 genera from 12 phyla represented. Taxonomic diversity in our study was broadly consistent with metagenomic studies of saliva. Proteins mapped to 20 KEGG pathways, with carbohydrate metabolism, amino acid metabolism, energy metabolism, translation, membrane transport, and signal transduction most represented. The communities sampled appear to be actively engaged in glycolysis and protein synthesis. This first deep metaproteomic catalog from human salivary supernatant provides a baseline for future studies of shifts in microbial diversity and protein activities potentially associated with oral disease.

Novel In Situ Collection of Tumor Interstitial Fluid from a Head and Neck Squamous Carcinoma Reveals a Unique Proteome with Diagnostic Potential.

INTRODUCTION: Tumors lack normal drainage of secreted fluids and consequently build up tumor interstitial fluid (TIF). Unlike other bodily fluids, TIF likely contains a high proportion of tumor-specific proteins with potential as biomarkers. METHODS: Here, we evaluated a novel technique using a unique ultrafiltration catheter for in situ collection of TIF and used it to generate the first catalog of TIF proteins from a head and neck squamous cell carcinoma (HNSCC). To maximize proteomic coverage, TIF was immunodepleted for high abundance proteins and digested with trypsin, and peptides were fractionated in three dimensions prior to mass spectrometry. RESULTS: We identified 525 proteins with high confidence. The HNSCC TIF proteome was distinct compared to proteomes of other bodily fluids. It contained a relatively high proportion of proteins annotated by Gene Ontology as "extracellular" compared to other secreted fluid and cellular proteomes, indicating minimal cell lysis from our in situ collection technique. Several proteins identified are putative biomarkers of HNSCC, supporting our catalog's value as a source of potential biomarkers. CONCLUSIONS: In all, we demonstrate a reliable new technique for in situ TIF collection and provide the first HNSCC TIF protein catalog with value as a guide for others seeking to develop tumor biomarkers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12014-010-9050-3) contains supplementary material, which is available to authorized users.

Targeted 18O-labeling for improved proteomic analysis of carbonylated peptides by mass spectrometry.

Proteomic characterization of carbonylated amino acid sites currently relies on confidently matching tandem mass spectra (MS(2)) to peptides within a sequence database. Although effective to some degree, reliable proteomic characterization of carbonylated peptides using this approach remains a challenge needing new, complementary solutions. To this end, we developed a method based on partial (18)O-labeling of reactive carbonyl modifications, which produces a unique isotope signature in mass spectra of carbonylated peptides and enables their detection without reliance on matching MS(2) spectra to a peptide sequence. Key to our method were optimized measures for eliminating trypsin-catalyzed incorporation of (18)O at peptide C-termini, and for stabilizing the incorporated (18)O within the carbonyl modification to prevent its loss during liquid chromatography separation. Applying our method to a rat skeletal muscle homogenate treated with the carbonyl modification 4-hyroxynonenal (4-HNE), we demonstrated its compatibility with solid-phase hydrazide enrichment of carbonylated peptides from complex mixtures. Additionally, we demonstrated the value of (18)O isotope signatures for confirming HNE-modified peptide sequences matched via sequence database searching, and identifying modified peptides missed by MS(2) and/or sequence database searching. Combining our (18)O-labeling method with a customized automated software script, we systematically evaluated for the first time the efficiency of MS(2) and sequence database searching for identifying HNE-modified peptides. We estimated that less than half of the modified peptides selected for MS(2) were successfully identified. Collectively, our method and software should provide valuable new tools for investigators studying protein carbonylation via mass spectrometry-based proteomics.

Private management of a public service: what can be learned from the CROS experience?

In January 2001, Canadian Radiation Oncology Services (CROS) was awarded the first-ever contract for the private management of a publicly funded department of radiation oncology. CROS saw its first patient in February 2001 and its last patient in August 2003. As of June 30, 2003, CROS had seen 2,018 patients, saving $30 million when compared to out-of-country referral. This raises several important questions.

Accuracy of recorded tumor, node, and metastasis stage in a comprehensive cancer center.

PURPOSE: The benefits of recording the tumor, node, and metastasis (TNM) stages of cancer patients are well accepted, but little is known about how accurately this is performed. An audit was performed to determine the accuracy of recorded stage and to act as a baseline before the implementation of an education program. PATIENTS AND METHODS: All new patient referrals to Princess Margaret Hospital between July 1 and August 31, 1997, were reviewed. An audit panel composed of five health record technicians (HRTs) and 10 doctors was assembled. Each auditor reviewed 10% of the health record. If there was a discrepancy between the stage in the health record and the auditor stage, then the final stage was determined by the audit committee. Analysis of the agreement between the health record, the physician auditor, the HRT auditor, and the final stage was performed. RESULTS: A total of 855 patients were referred with a new diagnosis of a malignancy for which there was a TNM stage system; 833 patients (97.4%) had a stage assigned. There was agreement between the health record stage and final stage in 80% (95% confidence interval [CI], 77% to 82%) of cases for clinical stage, compared with 90% (95% CI, 87% to 92%) for pathologic stage. Of the major site groups, lung was the least accurately recorded. The most common major discrepancies were due to the recording of X when a definite category could be assigned. CONCLUSION: This audit demonstrates the importance of staging and provides impetus to develop staging guidelines and education programs.