Risk-based lung cancer screening performance in a universal healthcare setting.

Globally, lung cancer is the leading cause of cancer death. Previous trials demonstrated that low-dose computed tomography lung cancer screening of high-risk individuals can reduce lung cancer mortality by 20% or more. Lung cancer screening has been approved by major guidelines in the United States, and over 4,000 sites offer screening. Adoption of lung screening outside the United States has, until recently, been slow. Between June 2017 and May 2019, the Ontario Lung Cancer Screening Pilot successfully recruited 7,768 individuals at high risk identified by using the PLCOm2012noRace lung cancer risk prediction model. In total, 4,451 participants were successfully screened, retained and provided with high-quality follow-up, including appropriate treatment. In the Ontario Lung Cancer Screening Pilot, the lung cancer detection rate and the proportion of early-stage cancers were 2.4% and 79.2%, respectively; serious harms were infrequent; and sensitivity to detect lung cancers was 95.3% or more. With abnormal scans defined as ones leading to diagnostic investigation, specificity was 95.5% (positive predictive value, 35.1%), and adherence to annual recall and early surveillance scans and clinical investigations were high (>85%). The Ontario Lung Cancer Screening Pilot provides insights into how a risk-based organized lung screening program can be implemented in a large, diverse, populous geographic area within a universal healthcare system.

[18F]FDG PET/CT in the Initial Staging and Restaging of Soft-Tissue or Bone Sarcoma in Patients with Negative or Equivocal Findings for Metastases or Limited Recurrence on Conventional Work-up: Results of a Prospective Multicenter Registry.

The purpose of this study was to determine the impact of [18F]FDG PET/CT on the initial staging, restaging, clinical management, and outcomes of patients with soft-tissue and bone sarcomas. Methods: This single-arm, prospective multicenter registry enrolled 304 patients with 320 [18F]FDG PET/CT scans (November 2018 to October 2021). Eligibility included the initial staging of a grade 2 or higher or ungradable soft-tissue or bone sarcoma, with negative or equivocal findings for nodal or distant metastases on conventional imaging before curative-intent therapy, or restaging of patients with a history of treated sarcoma with a suspicion or confirmation of local recurrence or limited metastatic disease who were being considered for curative-intent or salvage therapy. The presence of local recurrence or metastases on [18F]FDG PET/CT was recorded. Clinical management after [18F]FDG PET/CT compared with pre-[18F]FDG PET/CT planned management and quantitative metabolic tumor parameters (SUVmax, metabolic tumor volume, total lesion glycolysis) were correlated with the outcome data for 171 patients. Results: At the initial staging, [18F]FDG PET/CT detected metastases in 17 of 105 patients (16.2%) with no metastases on conventional work-up and confirmed metastases in 44 of 92 patients (47.8%) with equivocal findings for metastases. At the time of restaging, [18F]FDG PET/CT detected local recurrence in 37 of 123 patients (30.1%) and distant metastases in 71 of 123 patients (57.7%). Overall, the change in treatment intent and treatment type was recorded in 64 of 171 cases (37.4%) and 56 of 171 cases (32.8%), respectively. The presence of metastases on [18F]FDG PET/CT was associated with shorter progression-free survival at the initial staging (P = 0.04) and shorter overall survival at the time of recurrence (P = 0.002). All quantitative metabolic tumor parameters correlated with progression-free survival and overall survival. Conclusion: [18F]FDG PET/CT frequently detects additional sites of disease compared with conventional imaging in patients with sarcomas that were being considered for curative-intent or salvage therapy. This increased detection impacts the clinical management in a third of patients referred for initial staging or presumed limited recurrence after primary therapy. The presence of metastases on [18F]FDG PET/CT is associated with poorer outcomes.

Delivery of Cancer Care in Ontario, Canada, During the First Year of the COVID-19 Pandemic.

Importance: The COVID-19 pandemic has impacted cancer systems worldwide. Quantifying the changes is critical to informing the delivery of care while the pandemic continues, as well as for system recovery and future pandemic planning. Objective: To quantify change in the delivery of cancer services across the continuum of care during the COVID-19 pandemic. Design, Setting, and Participants: This population-based cohort study assessed cancer screening, imaging, diagnostic, treatment, and psychosocial oncological care services delivered in pediatric and adult populations in Ontario, Canada (population 14.7 million), from April 1, 2019, to March 1, 2021. Data were analyzed from May 1 to July 31, 2021. Exposures: COVID-19 pandemic. Main Outcomes and Measures: Cancer service volumes from the first year of the COVID-19 pandemic, defined as April 1, 2020, to March 31, 2021, were compared with volumes during a prepandemic period of April 1, 2019, to March 31, 2020. Results: During the first year of the pandemic, there were a total of 4 476 693 cancer care services, compared with 5 644 105 services in the year prior, a difference of 20.7% fewer services of cancer care, representing a potential backlog of 1 167 412 cancer services. While there were less pronounced changes in systemic treatments, emergency and urgent imaging examinations (eg, 1.9% more parenteral systemic treatments) and surgical procedures (eg, 65% more urgent surgical procedures), major reductions were observed for most services beginning in March 2020. Compared with the year prior, during the first pandemic year, cancer screenings were reduced by 42.4% (-1 016 181 screening tests), cancer treatment surgical procedures by 14.1% (-8020 procedures), and radiation treatment visits by 21.0% (-141 629 visits). Biopsies to confirm cancer decreased by up to 41.2% and surgical cancer resections by up to 27.8% during the first pandemic wave. New consultation volumes also decreased, such as for systemic treatment (-8.2%) and radiation treatment (-9.3%). The use of virtual cancer care increased for systemic treatment and radiation treatment and psychosocial oncological care visits, increasing from 0% to 20% of total new or follow-up visits prior to the pandemic up to 78% of total visits in the first pandemic year. Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, large reductions in cancer service volumes were observed. While most services recovered to prepandemic levels at the end of the first pandemic year, a substantial care deficit likely accrued. The anticipated downstream morbidity and mortality associated with this deficit underscore the urgent need to address the backlog and recover cancer care and warrant further study.

Effect of 18F-DCFPyL PET/CT on the Management of Patients with Recurrent Prostate Cancer: Results of a Prospective Multicenter Registry Trial.

Background The high positivity rate of prostate-specific membrane antigen (PSMA) PET in the setting of biochemical failure (BCF), even when conventional imaging is negative, is promising. Purpose To assess the disease detection rate of PSMA-based PET/CT with fluorine 18-DCFPyL as a radiotracer and the PET-directed management change in men with suspected limited recurrent prostate cancer. Materials and Methods This prospective multicenter registry (Ontario PSMA-PET Registry for Recurrent Prostate Cancer, or PREP) enrolled men with BCF after primary therapy (radical prostatectomy plus or minus salvage radiation therapy or primary radiation therapy) and zero to four disease sites at conventional imaging (CT and bone scintigraphy). The positivity rate of PSMA PET according to serum prostate-specific antigen (PSA) level; frequency of local-egional, oligometastatic, and extensive metastatic recurrence; and rate of change in management after PET findings were recorded. The nonparametric Mood median test was used to assess the association between serum PSA level and change in management. Results A total of 1289 men (median age, 71 years [interquartile range, 65-75 years]) were evaluated. PSMA PET helped detect disease in 841 of 1289 men (65%) and in 615 of 999 men (62%) with negative conventional imaging. The recurrence detection rates according to serum PSA level at enrollment were 38% (160 of 424 men), 63% (107 of 171 men), and 83% (573 of 692 men) for PSA under 0.5 ng/mL, 0.5-1.0 ng/mL, and above 1.0 ng/mL, respectively. At PSMA PET, 399 of 1289 men (31%) had local-regional recurrence, 314 (24%) had oligometastatic disease, and 128 (10%) had extensive metastases. Following PET examination, a change in planned management was recorded in 748 of 1289 men (58%), and in 371 of 1250 men (30%), there was a change in management intent, more commonly from palliative to potentially curative intent (255 of 1289 men [20%]). Conclusion Prostate-specific membrane antigen PET helped detect additional sites of disease compared with conventional imaging in approximately 60% of men with biochemical failure and suspected low-volume metastatic disease, resulting in frequent change in management, including a change from palliative to curative or radical intent therapy in 20% of men. Long-term follow-up is needed to determine whether this impacts disease control. Clinical trial registration no. NCT03718260 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Civelek in this issue.

Establishing a Provincial Registry for Recurrent Prostate Cancer: Providing Access to PSMA PET/CT in Ontario, Canada.

Prostate Specific Membrane Antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is becoming established as a standard of care for the (re)staging of high-risk primary and prostate cancer recurrence after primary therapy. Despite the favorable performance of this imaging modality with high accuracy in disease detection, the availability of PSMA PET/CT varies across jurisdictions worldwide due to variability in the selection of PSMA PET/CT agent, regulatory approvals and funding. In Canada, PSMA based radiopharmaceuticals are still considered investigational new drug (IND), creating limitations in the deployment of these promising imaging agents. While regulatory approval rests with Health Canada, as a single payer health system, funding for Health Canada approved drugs and devices is decided by Provincial Health Ministries. Ontario Health (Cancer Care Ontario) (OH-CCO) is the agency of the Ministry of Health (MOH) in Ontario responsible for making recommendations to the MOH around the organization and funding of cancer services within Ontario (population of 15 million), and the PET Steering Committee of OH-CCO is responsible for providing recommendations on the introduction of new PET radiopharmaceuticals and indications. For Health Canada approved PET radiopharmaceuticals like 18F-FDG, OH-CCO (on behalf of the MOH) provides coverage based on levels of evidence and specific PET Registries are established to aid in real-world evidence collection to inform OH-CCO regarding emerging PET applications. In the case of PSMA PET/CT, adapting this model to an IND PSMA PET/CT agent, 18F-DCFPyL, necessitated the creation of a hybrid Registry-Study model to leverage the existing OH-CCO Registry structure while respecting the need for a Health Canada Clinical Trials Application (CTA) for the deployment of this agent in the province. Within the first 2 years of the registry, over 1700 men have been imaged resulting in a change in management (compared to pre-PET management plans) in over half of the men imaged. In this article, we describe the organization and deployment of the PSMA PET/CT (PREP) Registry throughout the province to provide access for men with suspected prostate cancer recurrence along with key stakeholder perspectives and preliminary results.

The effect of diagnostic assessment programs on the diagnosis and treatment of patients with lung cancer in Ontario, Canada.

INTRODUCTION: Diagnostic assessment programs (DAPs) were implemented in Ontario, Canada, to improve the efficiency of the lung cancer care continuum. We compared the efficiency and effectiveness of care provided to patients in DAPs relative to usual care (non-DAPs). METHODS: Lung cancer patients diagnosed between 2014 and 2016 were identified from the Ontario Cancer Registry. Using administrative databases, we identified various health-care encounters 6 months before diagnosis until the start of treatment and compared utilization patterns, timing, and overall survival between DAP and non-DAP patients. RESULTS: DAP patients were younger (P < 0.0001), had fewer comorbidities (P = 0.0006), and were more likely to have early-stage disease (36% vs. 25%) than non-DAP patients. Although DAP patients had a similar time until diagnosis as non-DAP patients, the time until treatment was 8.5 days shorter for DAP patients. DAP patients were more likely to receive diagnostic tests and specialist consultations and less likely to have duplicate chest imaging. DAP patients were more likely to receive brain imaging. Among early-stage lung cancers, brain imaging was high (74% for DAP and 67% for non-DAP), exceeding guideline recommendations. After adjustment for clinical and demographic factors, DAP patients had better overall survival than non-DAP patients (hazard ratio [HR]: 0.79 [0.76-0.82]), but this benefit was lost after adjusting for emergency presentation (HR: 0.96 [0.92-1.00]). A longer time until treatment was associated with better overall survival. CONCLUSION: DAPs provided earlier treatment and better access to care, potentially improving survival. Quality improvement opportunities include reducing unnecessary or duplicate testing and characterizing patients who are diagnosed emergently.

A comparative analysis: international variation in PET-CT service provision in oncology-an International Cancer Benchmarking Partnership study.

OBJECTIVE: To explore differences in position emission tomography-computed tomography (PET-CT) service provision internationally to further understand the impact variation may have upon cancer services. To identify areas of further exploration for researchers and policymakers to optimize PET-CT services and improve the quality of cancer services. DESIGN: Comparative analysis using data based on pre-defined PET-CT service metrics from PET-CT stakeholders across seven countries. This was further informed via document analysis of clinical indication guidance and expert consensus through round-table discussions of relevant PET-CT stakeholders. Descriptive comparative analyses were produced on use, capacity and indication guidance for PET-CT services between jurisdictions. SETTING: PET-CT services across 21 jurisdictions in seven countries (Australia, Denmark, Canada, Ireland, New Zealand, Norway and the UK). PARTICIPANTS: None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULTS: PET-CT service provision has grown over the period 2006-2017, but scale of increase in capacity and demand is variable. Clinical indication guidance varied across countries, particularly for small-cell lung cancer staging and the specific acknowledgement of gastric cancer within oesophagogastric cancers. There is limited and inconsistent data capture, coding, accessibility and availability of PET-CT activity across countries studied. CONCLUSIONS: Variation in PET-CT scanner quantity, acquisition over time and guidance upon use exists internationally. There is a lack of routinely captured and accessible PET-CT data across the International Cancer Benchmarking Partnership countries due to inconsistent data definitions, data linkage issues, uncertain coverage of data and lack of specific coding. This is a barrier in improving the quality of PET-CT services globally. There needs to be greater, richer data capture of diagnostic and staging tools to facilitate learning of best practice and optimize cancer services.

The impact of synchronous malignancies on survival in patients with early stage curable non-small-cell lung cancer.

BACKGROUND: To determine if synchronous extrapulmonary malignancies in early stage lung cancer impact survival and cost of care in the current era of improved therapies and diagnostics. METHODS: Patients with stage I and II lung cancer were identified from the Ontario Cancer Registry and prognostic factors were obtained from provincial health administrative databases. Synchronous extrapulmonary malignancies were defined as those detected within 6 months from diagnosis of the lung primary. Survival was calculated using the Kaplan-Meier method and examined based on a 6-month landmark time point. The log-rank test and Cox proportional hazards regression was used to examine the effect of synchronous primaries on survival, univariately and after adjusting for prognostic factors. Cost of care was calculated by summing fees for all provincially funded services over 3 years. RESULTS: In a cohort of 6890 patients, those with synchronous malignancy had a HR of 1.32 (p = 0.026) for death in stage I patients, adjusted for other factors, while no association was found for stage II patients (HR=1.00, p = 0.99). 18F-FDG-PET/CT up to 6 months prior to lung cancer diagnosis had a HR of 0.84 (p = 0.003) for death adjusted for other factors. 3-year costs of care for these patients were $79,540 versus $54,520 in those without a synchronous malignancy (p<0.001). CONCLUSION: Extrapulmonary malignancies in stage I lung cancer patients may negatively impact survival with no such association for stage II patients. 18F-FDG-PET/CT performed before lung cancer diagnosis is associated with better survival. Cost of care is higher in patients with synchronous malignancies.

Impact of 18F-fluorodeoxyglucose PET/CT in the management of patients with plasma cell disorders.

OBJECTIVES: To evaluate the impact of F-fluorodeoxyglucose PET/CT examinations on the management of patients with plasma cell disorders. METHODS: This is a retrospective review of patients in a provincial database with PET/CT performed for plasma cell disorders between 2011 and 2018. The impact of PET/CT on actual patient management and outcome was assessed by two independent readers who compared planned pre-PET/CT management, documented at time of PET/CT requisition, to actual management received through linkages to administrative databases. PET/CT was considered of high impact if it altered the provision of active treatment, changed the modality of treatment or chemotherapy regimen. Change in management and the proportion of patients with high impact PET/CT were assessed. RESULTS: There were 44 patients with plasma cell disorders, including multiple myeloma, solitary plasmacytoma, Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes syndrome, or monoclonal gammopathy of undetermined significance or biclonal gammopathy of undetermined significance. Management was altered after 38/56 (67.9%) PET/CT scans. Considering just the initial PET/CT scan in patients who underwent multiple scans, 31/44 (70.5%) patients had their management altered subsequent to PET/CT. CONCLUSION: PET/CT resulted in a change in planned management in more than two-thirds of patients with plasma cell disorders in the current selected patient cohort. These results should be validated in a larger prospective trial.

Effect of PET/CT on the Management and Outcomes of Participants with Hodgkin and Aggressive Non-Hodgkin Lymphoma: A Multicenter Registry.

Purpose To determine the relationship of PET/CT staging to the management and outcomes of participants with apparent limited-stage (LS) Hodgkin lymphoma (HL) or aggressive non-HL (ANHL) treated with curative intent. Materials and Methods This prospective multicenter registry included 850 participants (467 men and 383 women; median age, 54.1 years) from nine centers who had LS HL or ANHL on the basis of clinical data and CT, or with equivocal CT for advanced stage, who were considered for curative-intent first-line therapy. Participants were recruited between May 1, 2013, and December 31, 2015. Pre-PET/CT treatment plan was compared with treatment provided. Survival and second-line therapy initiation were compared with an historical control pool staged by using CT alone. Administrative data sources were used to control for baseline characteristics. Outcomes were assessed by using adjusted Cox proportional hazards regression and propensity score matching. Results PET/CT helped to upstage 150 of 850 participants (17.6%). There was a change in planned therapy in 224 of 580 (38.6%) of participants after PET/CT. There was a lower 1-year mortality for participants with ANHL in the PET/CT versus CT cohort (hazard ratio, 0.63; 95% confidence interval: 0.40, 1.0; P < .05) and for those with LS at PET/CT compared with those with LS at CT (hazard ratio, 0.40; 95% confidence interval: 0.21, 0.74; P = .004). For participants with HL, no 1-year outcome difference was found (P = .16). Conclusion PET/CT helped to upstage approximately 18% of participants and planned management was frequently altered. Participants with aggressive non-Hodgkin lymphoma whose first-line therapy was guided by PET/CT had significantly better survival compared with participants whose treatment was guided by CT. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Scott in this issue.

[18 F]-FDG PET/CT in the staging and management of indolent lymphoma: A prospective multicenter PET registry study.

BACKGROUND: To measure the clinical impact of pretreatment fludeoxyglucose positron emission tomography/computed tomography (PET/CT) on the staging and management of apparent limited stage indolent lymphoma being considered for curative radiation therapy. METHODS: We conducted a prospective multicenter registry study that included 197 patients accrued between May 1, 2012, and December 31, 2015. Pre-PET/CT stage, determined by clinical and CT data, was documented. If pre-PET/CT stage was indeterminate, a stage was assigned to the patient by the referring oncologist according to best clinical judgment and treatment intent. After PET/CT, revised stage and planned management were recorded and compared with data on actual treatment received available through provincial databases (n = 155). RESULTS: PET/CT resulted in the upstaging of 47 (23.9%) patients with presumed limited stage disease (stage I-II) to advanced stage disease (stage III-IV) (P < .0001). Ten (5.1%) patients were downstaged by PET/CT, 4 of whom migrated from advanced to limited stage disease. Twenty-eight (14.2%) patients with a specific pre-PET/CT stage had equivocal PET/CT findings that required further evaluation to confirm disease extent. After PET/CT, 95 (61.3%) patients were planned to receive active treatment. Of the 59 patients planned for radiotherapy alone post-PET/CT, 34 (57.6%) received this treatment (P = .002), and nearly 80% of them (n = 27) had confirmed limited stage disease. CONCLUSION: PET/CT has a significant impact on staging and management in patients with apparent limited stage indolent lymphoma who are being considered for curative radiotherapy. PET/CT should be routinely incorporated into the workup of these patients. Cancer 2017;123:2860-66. © 2017 American Cancer Society.

Effect of chemotherapy on the impact of FDG-PET/CT in selection of patients for surgical resection of colorectal liver metastases: single center analysis of PET-CAM randomized trial.

The largest randomized controlled trial (RCT) on the effect of FDG-PET on surgical management for metastatic colorectal adenocarcinoma to liver ("PET-CAM") reported only a modest change in surgical management (8%). PURPOSE: To explore the relationship between prior chemotherapy and detection of metastatic disease on PET in patients from PET-CAM. Secondary aim: to determine whether centralized imaging interpretation could have impacted trial results. METHODS: The study included 120 patients from a single institution. Local PET interpretation (PET-L) was recorded from the original database. Retrospective PET interpretation was performed independently by at least one additional reader (PET-C). The presence of extrahepatic disease (EHD) and significant additional liver metastases (=SALM), defined as metastases not originally planned for resection, was recorded. Patients were stratified to responders to recent chemotherapy (Group R) versus all others (Group O) according to surgical pathology and RECIST criteria. RESULTS: Thirty-seven of 50 patients who received recent chemotherapy (<90 days) were responders (Group R). EHD was present in 30/120 (25%) patients. There was no difference in detection of EHD on PET-L (7/37;18.9%), PET-C (7/37;18.9%), and CT (4/37;10.8%) for Group R (p = 0.375), but in Group O more EHD was detected on both PET-L (15/83;18.1%) and PET-C (22/83;26.5%) than CT (8/83;9.6%); p = 0.039 and p < 0.001, respectively. For the entire cohort, PET-L and PET-C detected EHD and/or SALM not reported on CT in 14 (11.7%) and 22 (18.3%) patients. CONCLUSION: The impact of recent chemotherapy on detection of colorectal metastases with PET suggests that the utility of PET in patient selection for liver resection in the prior PET-CAM-RCT may have been underestimated.

18F-FDG-PET/CT in the Staging and Management of Melanoma: A Prospective Multicenter Ontario PET Registry Study.

PURPOSE: The Ontario PET Registry was established to provide evidence on the clinical impact of 18-FDG-PET/CT (PET) imaging to inform Ontario Health Insurance Plan funding decisions. The melanoma registry assessed the use of melanoma staging by PET in advanced or high-risk melanoma as a useful adjunct to clinical and standard radiologic investigation. MATERIALS AND METHODS: Between January 2011 and July 2013, approximately 319 consecutive patients with potentially resectable localized high-risk melanoma or recurrent disease under consideration for metastasectomy underwent PET imaging for staging across 9 institutions in Ontario. Pre-PET stage information was provided by the referring clinician and compared with post-PET stage. The ability of PET to reclassify disease from M0 to M1 status was assessed. The registry data were then linked to provincial administrative databases using deidentified health insurance numbers to determine PET stage-based rates of systemic therapy, radiotherapy, and surgery. RESULTS: There was a significant increase in stage to M1 status after PET in 56 of 319 patients (17.6%) (P < 0.0001). There was no significant relationship between upstaging with PET and the proportion of patients receiving radiation therapy (P = 0.066) or systemic therapy (P = 0.072). There was a significant relationship between upstaging with PET and the proportion of patients undergoing surgical resection of metastases distant to the primary melanoma site (P = 0.034). CONCLUSIONS: This prospective, multicenter registry of high-risk or advanced melanoma found that PET significantly upstages patients and impacts surgical management.

Prostate cancer localization with multispectral MRI using cost-sensitive support vector machines and conditional random fields.

Prostate cancer is a leading cause of cancer death for men in the United States. Fortunately, the survival rate for early diagnosed patients is relatively high. Therefore, in vivo imaging plays an important role for the detection and treatment of the disease. Accurate prostate cancer localization with noninvasive imaging can be used to guide biopsy, radiotherapy, and surgery as well as to monitor disease progression. Magnetic resonance imaging (MRI) performed with an endorectal coil provides higher prostate cancer localization accuracy, when compared to transrectal ultrasound (TRUS). However, in general, a single type of MRI is not sufficient for reliable tumor localization. As an alternative, multispectral MRI, i.e., the use of multiple MRI-derived datasets, has emerged as a promising noninvasive imaging technique for the localization of prostate cancer; however almost all studies are with human readers. There is a significant inter and intraobserver variability for human readers, and it is substantially difficult for humans to analyze the large dataset of multispectral MRI. To solve these problems, this study presents an automated localization method using cost-sensitive support vector machines (SVMs) and shows that this method results in improved localization accuracy than classical SVM. Additionally, we develop a new segmentation method by combining conditional random fields (CRF) with a cost-sensitive framework and show that our method further improves cost-sensitive SVM results by incorporating spatial information. We test SVM, cost-sensitive SVM, and the proposed cost-sensitive CRF on multispectral MRI datasets acquired from 21 biopsy-confirmed cancer patients. Our results show that multispectral MRI helps to increase the accuracy of prostate cancer localization when compared to single MR images; and that using advanced methods such as cost-sensitive SVM as well as the proposed cost-sensitive CRF can boost the performance significantly when compared to SVM.

Supervised and unsupervised methods for prostate cancer segmentation with multispectral MRI.

PURPOSE: Magnetic resonance imaging (MRI) has been proposed as a promising alternative to transrectal ultrasound for the detection and localization of prostate cancer and fusing the information from multispectral MR images is currently an active research area. In this study, the goal is to develop automated methods that combine the pharmacokinetic parameters derived from dynamic contrast enhanced (DCE) MRI with quantitative T2 MRI and diffusion weighted imaging (DWI) in contrast to most of the studies which were performed with human readers. The main advantages of the automated methods are that the observer variability is removed and easily reproducible results can be efficiently obtained when the methods are applied to a test data. The goal is also to compare the performance of automated supervised and unsupervised methods for prostate cancer localization with multispectral MRI. METHODS: The authors use multispectral MRI data from 20 patients with biopsy-confirmed prostate cancer patients, and the image set consists of parameters derived from T2, DWI, and DCE-MRI. The authors utilize large margin classifiers for prostate cancer segmentation and compare them to an unsupervised method the authors have previously developed. The authors also develop thresholding schemes to tune support vector machines (SVMs) and their probabilistic counterparts, relevance vector machines (RVMs), for an improved performance with respect to a selected criterion. Moreover, the authors apply a thresholding method to make the unsupervised fuzzy Markov random fields method fully automatic. RESULTS: The authors have developed a supervised machine learning method that performs better than the previously developed unsupervised method and, additionally, have found that there is no significant difference between the SVM and RVM segmentation results. The results also show that the proposed methods for threshold selection can be used to tune the automated segmentation methods to optimize results for certain criteria such as accuracy or sensitivity. The test results of the automated algorithms indicate that using multispectral MRI improves prostate cancer segmentation performance when compared to single MR images, a result similar to the human reader studies that were performed before. CONCLUSIONS: The automated methods presented here can help diagnose and detect prostate cancer, and improve segmentation results. For that purpose, multispectral MRI provides better information about cancer and normal regions in the prostate when compared to methods that use single MRI techniques; thus, the different MRI measurements provide complementary information in the automated methods. Moreover, the use of supervised algorithms in such automated methods remain a good alternative to the use of unsupervised algorithms.

Prostate tissue composition and MR measurements: investigating the relationships between ADC, T2, K(trans), v(e), and corresponding histologic features.

PURPOSE: To investigate relationships between magnetic resonance (MR) imaging measurements and the underlying composition of normal and malignant prostate tissue. MATERIALS AND METHODS: Twenty-four patients (median age, 63 years; age range, 44-72 years) gave informed consent to be examined for this research ethics board-approved study. Before undergoing prostatectomy, patients were examined with T2-weighted, diffusion-weighted, T2 mapping, and dynamic contrast material-enhanced MR imaging at 1.5 T. Maps of apparent diffusion coefficient (ADC), T2, volume transfer constant (K(trans)), and extravascular extracellular space (v(e)) were calculated. Whole-mount hematoxylin-eosin-stained sections were generated and digitized at histologic resolution. Percentage areas of tissue components (nuclei, cytoplasm, stroma, luminal space) were measured by using image segmentation. Corresponding regions on MR images and histologic specimens were defined by using anatomically defined segments in peripheral zone (PZ) and central gland tissue. Cancer and normal PZ regions were identified at histopathologic analysis. Each MR parameter-histologic tissue component pair was assessed by using linear mixed-effects models, and cancer versus normal PZ values were compared by using nonparametric tests. RESULTS: ADC and T2 were inversely related to percentage area of nuclei and percentage area of cytoplasm and positively related to percentage area of luminal space (P < or = .01). These trends were reversed for K(trans) (P < .001). K(trans) had a significantly negative (P = .01) slope versus percentage area of stroma, and v(e) had a positive (P = .008) slope versus percentage area of stroma. The v(e) was inversely proportional to the percentage area of nuclei (P = .05). All MR imaging parameters (P < or = .05) and the percentage areas of all tissue components (P < or = .001) except stroma (P > .48) were significantly different between cancer and normal PZ tissue. CONCLUSION: MR imaging-derived parameters measured in the prostate were significantly related to the proportion of specific histologic components that differ between normal and malignant PZ tissue. These relationships may help define imaging-related histologic prognostic parameters for prostate cancer.

Focal laser ablation for prostate cancer followed by radical prostatectomy: validation of focal therapy and imaging accuracy.

An increased incidence of low-risk prostate cancer (PCa) has led investigators to develop focal therapy as a management option for PCa. We evaluated the effects of focal laser ablation (FLA) on PCa tissue and the accuracy of magnetic resonance imaging (MRI) in determining ablated lesion volume by comparing the whole-mount histology and MRI in four patients that underwent FLA followed by radical prostatectomy. Ablated areas were characterized by homogeneous coagulation necrosis. The MRI-calculated ablated volume correlated well with histopathology. We found that FLA creates confluent ablation with no evidence of viable cells in treated regions. Postablation MRI is able to determine the ablation accurately.

T2*-weighted and arterial spin labeling MRI of calf muscles in healthy volunteers and patients with chronic exertional compartment syndrome: preliminary experience.

OBJECTIVE: The purpose of our study was to assess temporal changes with exercise in T2* and arterial spin labeling signals in patients with chronic exertional compartment syndrome of the anterior compartment of the lower leg and in control subjects using T2* mapping and arterial spin labeling MRI. SUBJECTS AND METHODS: This prospective study was approved by the institutional research ethics board. Ten control subjects (five women and five men; mean age, 29.0 years) and nine patients with chronic exertional compartment syndrome (three women and six men; mean age, 33.7 years) gave informed written consent and underwent MRI of the calf muscles using an axial T2*-weighted multiecho gradient-recalled echo and a flow-sensitive alternating inversion recovery sequence with echo-planar imaging readouts before (baseline) and 3, 6, 9, 12, and 15 minutes after exercise. T2* and arterial spin labeling signal changes (DeltaT2* and DeltaASL, respectively) over time were calculated relative to the baseline examination. DeltaT2* and DeltaASL between patients and control subjects were compared using the Student's t test. RESULTS: In both patients and control subjects, DeltaT2* and DeltaASL showed a peak at 3 minutes after exercise, followed by a decrease over time. The maximum DeltaT2* was 26% and 29% for patients and control subjects, respectively. The maximum DeltaASL was 183% and 224% for patients and control subjects, respectively. After 15 minutes, arterial spin labeling signal returned to baseline; however, T2* remained elevated (8% in patients; 10% in control subjects). No statistically significant differences between patients and control subjects in postexercise DeltaT2* and DeltaASL were found (p = 0.21-0.98). CONCLUSION: After calf muscle exercise, no statistically significant differences in T2* relaxation times or arterial spin labeling signal, indicative of differences in muscle oxygenation and perfusion status, were found between patients with chronic exertional compartment syndrome and control subjects.

Prostate cancer detection with multi-parametric MRI: logistic regression analysis of quantitative T2, diffusion-weighted imaging, and dynamic contrast-enhanced MRI.

PURPOSE: To develop a multi-parametric model suitable for prospectively identifying prostate cancer in peripheral zone (PZ) using magnetic resonance imaging (MRI). MATERIALS AND METHODS: Twenty-five radical prostatectomy patients (median age, 63 years; range, 44-72 years) had T2-weighted, diffusion-weighted imaging (DWI), T2-mapping, and dynamic contrast-enhanced (DCE) MRI at 1.5 Tesla (T) with endorectal coil to yield parameters apparent diffusion coefficient (ADC), T2, volume transfer constant (K(trans)) and extravascular extracellular volume fraction (v(e)). Whole-mount histology was generated from surgical specimens and PZ tumors delineated. Thirty-eight tumor outlines, one per tumor, and pathologically normal PZ regions were transferred to MR images. Receiver operating characteristic (ROC) curves were generated using all identified normal and tumor voxels. Step-wise logistic-regression modeling was performed, testing changes in deviance for significance. Areas under the ROC curves (A(z)) were used to evaluate and compare performance. RESULTS: The best-performing single-parameter was ADC (mean A(z) [95% confidence interval]: A(z,ADC): 0.689 [0.675, 0.702]; A(z,T2): 0.673 [0.659, 0.687]; A(z,Ktrans): 0.592 [0.578, 0.606]; A(z,ve): 0.543 [0.528, 0.557]). The optimal multi-parametric model, LR-3p, consisted of combining ADC, T2 and K(trans). Mean A(z,LR-3p) was 0.706 [0.692, 0.719], which was significantly higher than A(z,T2), A(z,Ktrans), and A(z,ve) (P < 0.002). A(z,LR-3p) tended to be greater than A(z,ADC), however, this result was not statistically significant (P = 0.090). CONCLUSION: Using logistic regression, an objective model capable of mapping PZ tumor with reasonable performance can be constructed.

Prostate cancer segmentation with simultaneous estimation of Markov random field parameters and class.

Prostate cancer is one of the leading causes of death from cancer among men in the United States. Currently, high-resolution magnetic resonance imaging (MRI) has been shown to have higher accuracy than trans-rectal ultrasound (TRUS) when used to ascertain the presence of prostate cancer. As MRI can provide both morphological and functional images for a tissue of interest, some researchers are exploring the uses of multispectral MRI to guide prostate biopsies and radiation therapy. However, success with prostate cancer localization based on current imaging methods has been limited due to overlap in feature space of benign and malignant tissues using any one MRI method and the interobserver variability. In this paper, we present a new unsupervised segmentation method for prostate cancer detection, using fuzzy Markov random fields (fuzzy MRFs) for the segmentation of multispectral MR prostate images. Typically, both hard and fuzzy MRF models have two groups of parameters to be estimated: the MRF parameters and class parameters for each pixel in the image. To date, these two parameters have been treated separately, and estimated in an alternating fashion. In this paper, we develop a new method to estimate the parameters defining the Markovian distribution of the measured data, while performing the data clustering simultaneously. We perform computer simulations on synthetic test images and multispectral MR prostate datasets to demonstrate the efficacy and efficiency of the proposed method and also provide a comparison with some of the commonly used methods.