Predictive role of diffusion-weighted MRI in the assessment of response to total neoadjuvant therapy in locally advanced rectal cancer.

OBJECTIVE: To investigate the predictive role of diffusion-weighted magnetic resonance imaging (DW-MRI) in the assessment of response to total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC). METHODS: In this single-center retrospective study, patients with LARC who underwent staging MRI and TNT were enrolled. MRI-based staging, tumor volume, and DWI-ADC values were analyzed. Patients were classified as complete responders (pCR) and non-complete responders (non-pCR), according to post-surgical outcome. Pre-treatment ADC values were compared to pathological outcome, post-treatment downstaging, and reduction of tumor volume. The diagnostic accuracy of DWI-ADC in differentiating between pCR and non-pCR groups was calculated with receiver operating characteristic (ROC) analysis. RESULTS: A total of 36 patients were evaluated (pCR, n = 20; non-pCR, n = 16). Pre-treatment ADC values were significantly different between the two groups (p = 0.034), while no association was found between pre-TNT tumor volume and pathological response. ADC values showed significant correlations with loco-regional downstaging after therapy (r = -0.537, p = 0.022), and with the reduction of tumor volume (r = -0.480, p = 0.044). ADC values were able to differentiate pCR from non-pCR patients with a sensitivity of 75% and specificity of 70%. CONCLUSIONS: ADC values on pre-treatment MRI were strongly associated with the outcome in patients with LARC, both in terms of pathological response and in loco-regional downstaging after TNT, suggesting the use of DW-MRI as a potential predictive tool of response to therapy. KEY POINTS: • ADC values of pre-TNT MRI examinations of patients with LARC were significantly associated with a pathological complete response (pCR) and with post-treatment regression of TNM staging. • An ADC value of 1.042 ×10-3 mm2/s was found to be the optimal cutoff value for discriminating between pCR and non-pCR patients, with a sensitivity of 75% and specificity of 70%. • DW-MRI proved to have a potential predictive role in the assessment of response to therapy in patients with LARC, throughout the analysis of ADC map values.

Tocilizumab effects in COVID-19 pneumonia: role of CT texture analysis in quantitative assessment of response to therapy.

PURPOSE: To evaluate CT and laboratory changes in COVID-19 patients treated with tocilizumab, compared to a control group, throughout a combined semiquantitative and texture analysis of images. MATERIALS AND METHODS: From March 11 to April 20, 2020, 57 SARS-CoV-2 positive patients were retrospectively compared: group T (n = 30) receiving tocilizumab and group non-T (n = 27) undergoing only antivirals/antimalarials. Chest-CT and laboratory findings were analyzed before and after treatment. CT evaluation included both semiquantitative scoring and texture analysis of all parenchymal lesions. Survival and recovery analyses were also provided with Kaplan-Meier method. RESULTS: In group T, no significant differences were found for CT score after treatment, while several texture features significantly changed, including mean attenuation (p < 0.0001), skewness (p < 0.0001), entropy (p = 0.0146) and higher-order parameters, suggesting considerable fading of parenchymal lesions. PaO2/FiO2 mean value significantly increased after treatment, from 240 ± 93 to 363 ± 107 (p = 0.0003), with parallel decrease in inflammatory biomarkers (CRP, D-dimer and LDH). In group non-T, CT scoring, texture and laboratory parameters showed significant worsening at follow-up. Findings were clinically associated with opposite trends between two groups, with reduction of severe cases in group T (from 21/30 to 5/30; p < 0.0001) as compared to a significant worsening in group non-T (severe cases increasing from 6/27 to 14/27; p = 0.0473). Probability of discharge was significantly higher in group T (p < 0.0001), as well as survival rate, although not statistically significant. CONCLUSIONS: Our results suggest the potential role of CT texture analysis for assessing response to treatment in COVID-19 pneumonia, using Tocilizumab, as compared to semiquantitative evaluation, providing insight into the intrinsic parenchymal changes.

CT colonography: preliminary assessment of a double-read paradigm that uses computer-aided detection as the first reader.

PURPOSE: To compare diagnostic performance and time efficiency of double-reading first-reader computer-aided detection (CAD) (DR FR CAD) followed by radiologist interpretation with that of an unassisted read using segmentally unblinded colonoscopy as reference standard. MATERIALS AND METHODS: The local ethical committee approved this study. Written consent to use examinations was obtained from patients. Three experienced radiologists searched for polyps 6 mm or larger in 155 computed tomographic (CT) colonographic studies (57 containing 10 masses and 79 polyps ≥ 6 mm). Reading was randomized to either unassisted read or DR FR CAD. Data sets were reread 6 weeks later by using the opposite paradigm. DR FR CAD consists of evaluation of CAD prompts, followed by fast two-dimensional review for mass detection. CAD sensitivity was calculated. Readers' diagnoses and reviewing times with and without CAD were compared by using McNemar and Student t tests, respectively. Association between missed polyps and lesion characteristics was explored with multiple regression analysis. RESULTS: With mean rate of 19 (standard deviation, 14; median, 15; range, 4-127) false-positive results per patient, CAD sensitivity was 90% for lesions 6 mm or larger. Readers' sensitivity and specificity for lesions 6 mm or larger were 74% (95% confidence interval [CI]: 65%, 84%) and 93% (95% CI: 89%, 97%), respectively, for the unassisted read and 77% (95% CI: 67%, 85%) and 90% (95% CI: 85%, 95%), respectively, for DR FR CAD (P = .343 and P = .189, respectively). Overall unassisted and DR FR CAD reviewing times were similar (243 vs 239 seconds; P = .623); DR FR CAD was faster when the number of CAD marks per patient was 20 or fewer (187 vs 220 seconds, P <01). Odds ratio of missing a polyp with CAD decreased as polyp size increased (0.6) and for polyps visible on both prone and supine scans (0.12); it increased for flat lesions (9.1). CONCLUSION: DR FR CAD paradigm had similar performance compared with unassisted interpretation but better time efficiency when 20 or fewer CAD prompts per patient were generated.

Colorectal cancer screening: the role of CT colonography.

Computed tomography colonography (CTC) in colorectal cancer (CRC) screening has two roles: one present and the other potential. The present role is, without any further discussion, the integration into established screening programs as a replacement for barium enema in the case of incomplete colonoscopy. The potential role is the use of CTC as a first-line screening method together with Fecal Occult Blood Test, sigmoidoscopy and colonoscopy. However, despite the fact that CTC has been officially endorsed for CRC screening of average-risk individuals by different scientific societies including the American Cancer Society, the American College of Radiology, and the US Multisociety Task Force on Colorectal Cancer, other entities, such as the US Preventive Services Task Force, have considered the evidence insufficient to justify its use as a mass screening method. Medicare has also recently denied reimbursement for CTC as a screening test. Nevertheless, multiple advantages exist for using CTC as a CRC screening test: high accuracy, full evaluation of the colon in virtually all patients, non-invasiveness, safety, patient comfort, detection of extracolonic findings and cost-effectiveness. The main potential drawback of a CTC screening is the exposure to ionizing radiation. However, this is not a major issue, since low-dose protocols are now routinely implemented, delivering a dose comparable or slightly superior to the annual radiation exposure of any individual. Indirect evidence exists that such a radiation exposure does not induce additional cancers.

Value-of-information analysis to guide future research in colorectal cancer screening.

PURPOSE: To identify the most useful areas for research in colorectal cancer (CRC) screening by using a value-of-information analysis. MATERIALS AND METHODS: Cost-effectiveness of screening strategies, including colonoscopy, computed tomographic (CT) colonography, flexible sigmoidoscopy, and barium enema examination, were compared by using a Markov model. Monetary net benefit (NB), a measure of cost-effectiveness, was calculated by multiplying effect (life-years gained) by willingness to pay (100,000 dollars per life-year gained) and subtracting cost. A value-of-information analysis was used to estimate the expected benefit of future research that would eliminate the decision uncertainty. RESULTS: In the reference-case analysis, colonoscopy was the optimal test with the highest NB (1945 dollars per subject invited for screening compared with 1862 dollars, 1717 dollars, and 1653 dollars for CT colonography, flexible sigmoidoscopy, and barium enema examination, respectively). Results of probabilistic sensitivity analysis indicated that colonoscopy was the optimal choice in only 45% of the simulated scenarios, whereas CT colonography, flexible sigmoidoscopy, and barium enema examination were the optimal strategies in 23%, 16%, and 15% of the scenarios, respectively. Only two parameters were responsible for most of this uncertainty about the optimal test for CRC screening: the increase in adherence with less invasive tests and CRC natural history. The expected societal monetary benefit of further research in these areas was estimated to be more than 15 billion dollars. CONCLUSION: Results of value-of-information analysis show that future research on the optimal test for CRC screening has a large societal impact. Priority should be given to research on the increase in adherence with screening by using less invasive tests and to better understanding of the natural history of CRC.

Impact of whole-body CT screening on the cost-effectiveness of CT colonography.

PURPOSE: To analyze the impact of adding computed tomographic (CT) imaging of the chest on the clinical effectiveness and cost-effectiveness of CT colonography to determine whether performing CT colonography and whole-body CT is a more clinically and cost-effective strategy than CT colonography alone when screening average-risk subjects. MATERIALS AND METHODS: A Markov model simulated the occurrence of colorectal neoplasia, extracolonic abominal-pelvic malignancy, lung cancer, coronary artery disease (CAD), and abdominal aortic aneurysm (AAA) in a cohort of 100,000 U.S. subjects aged 50 to 100 years. Cost-effectiveness of CT colonography and whole-body CT was compared with that of CT colonography alone; each test was assumed to be repeated every 10 years between ages of 50 and 80 years. RESULTS: Performing CT colonography and whole-body CT was more effective and costly than was CT colonography alone. The addition of chest CT was associated with a 22% increase in efficacy (life-years gained: 14,662 vs 11,990) and with a 48% increase in cost per person ($13,605 vs $9,223). Both strategies were cost effective as compared with no screening, with an incremental cost-effectiveness ratio (ICER) of $17,672 (CT colonography alone) and $44,337 (CT colonography and whole-body CT), respectively, but performing CT colonography and whole-body CT was not a cost-effective option when compared with CT colonography alone (ICER, $164,020). This was mainly a result of the high cost of false-positive follow-up for CAD and to the poor efficacy of lung cancer screening. Expected value of perfect information was $520 per patient. CONCLUSION: The addition of chest CT to CT colonography does not appear to be a cost-effective alternative. Further research is needed before whole-body CT can be recommended in clinical practice.

Impact of computer-aided detection on the cost-effectiveness of CT colonography.

PURPOSE: To analyze the cost-effectiveness of adding computer-aided detection (CAD) to a computed tomographic (CT) colonography screening program and to compare it with other options of colorectal cancer (CRC) prevention. MATERIALS AND METHODS: The cost-effectiveness of screening strategies by using CT colonography with and without CAD, flexible sigmoidoscopy (FS), and optical colonoscopy were compared by using a Markov-based computer model. In the model, a hypothetical population of 100,000 persons aged 50 years underwent colorectal screening every 10 years. Baseline sensitivities for both experienced and inexperienced readers and the incremental accuracy when adding CAD were estimated from a systematic review of the literature. RESULTS: At baseline, the addition of CAD resulted in 9% and 2% increases in CRC prevention rates for inexperienced and experienced readers, respectively, when compared with CT colonography without CAD. Assuming a CAD cost of $50 per CT colonography, the overall program costs increased by only 3%-5%, largely because of the substantial reduction in CRC-related costs. The incremental cost-effectiveness of CT colonography with CAD compared with CT colonography without CAD was $8661 and $61,354 per life-year gained for inexperienced and experienced readers, respectively. Optical colonoscopy was not a cost-effective alternative to CT colonography with CAD performed by experienced readers, with an incremental cost-effectiveness of $498,668 per life-year gained. CT colonography with CAD for inexperienced readers was more clinically effective and cost-effective than FS. At analysis, sensitivity of CT colonography with CAD for polyps 6 mm or larger was the most meaningful variable. CONCLUSION: The addition of CAD to CT colonography screening improves the CRC prevention rate, resulting in advantageous cost-effectiveness for screening. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/250/2/488/DC1.

Cost-effectiveness of upper gastrointestinal endoscopy according to the appropriateness of the indication.

OBJECTIVE: Application of appropriate indications for upper endoscopy (EGD) should conserve limited endoscopic resources. The cost-effectiveness of current guidelines for the detection of gastro-oesophageal cancer is unknown. The aim of this study was to assess the clinical and economic impact of ASGE and EPAGE guidelines in selecting patients referred for upper endoscopy relative to the detection of gastro-oesophageal cancer. MATERIAL AND METHODS: A decision analysis model was constructed to compare a strategy of not referring patients for EGD (with either an appropriate or inappropriate indication) with a policy of carrying out the requested EGD. Cancer prevalence in appropriate and inappropriate EGDs was estimated using a systematic review of the literature. Costs of EGD and cancer care were estimated from Medicare reimbursement data. RESULTS: The number of appropriate and inappropriate EGDs required to detect one case of cancer was 41 and 753, respectively, and to prevent one gastro-oesophageal cancer-related death the numbers were 571 and 11,111, respectively. The incremental cost-effectiveness ratios of appropriate and inappropriate EGDs as compared to a policy of not referring patients for endoscopy were $16,577 and $301,203, respectively, per life-year gained. CONCLUSIONS: For inappropriate EGD, the very low likelihood of cancer and the relatively high costs associated with this procedure argue against endoscopic referral.

Cost effectiveness of colonoscopy, based on the appropriateness of an indication.

BACKGROUND & AIMS: Determination of the appropriateness of an indication for colonoscopy has been advanced as a means to help rationalize the use of endoscopic resources. However, the efficacy and cost effectiveness of the current guidelines used to select patients for colonoscopy are largely unknown. The goal of this study was to assess the clinical and economic impact of American Society for Gastrointestinal Endoscopy and the European Panel on the appropriateness of Gastrointestinal Endoscopy appropriateness guidelines in selecting patients who are referred for colonoscopy, in relation to colorectal cancer (CRC) detection. METHODS: A decision-analysis model was constructed to compare colonoscopy strategies for "appropriate" indications with those for which colonoscopy is deemed "inappropriate" or "generally not indicated." A 50% cancer upstaging was modeled to simulate cancer progression for patients not referred for colonoscopy. CRC prevalence was estimated using a pooled data analysis based on a systematic review of the literature. Costs of colonoscopy and cancer care were estimated from Medicare reimbursement data. The number of colonoscopies needed to detect one case of cancer and to prevent one cancer-related death and incremental cost-effectiveness ratios (ICER), according to appropriateness categories, were computed in a simulated population of patients that were 60 years of age and referred for colonoscopy. RESULTS: The numbers of appropriate and inappropriate colonoscopies that needed to be performed to detect one patient with cancer were 18 and 93, respectively. Similarly, 115 and 617 colonoscopies would be needed, respectively, to prevent one CRC-related death. The ICER for appropriate and inappropriate colonoscopies, compared with a policy of not referring patients to colonoscopy, was $6154 and $31,807 per life-year gained, respectively. In a sensitivity analysis, only a reduction from the baseline value of 1.1% to 0.2% was associated with an ICER for inappropriate colonoscopy higher than $150,000. CONCLUSIONS: Current guidelines regarding the appropriateness of colonoscopy are relatively inefficient in excluding a clinically meaningful CRC risk for patients in whom colonoscopy is generally not indicated, raising serious concerns about their applicability to clinical practice.

Clinical management of small (6- to 9-mm) polyps detected at screening CT colonography: a cost-effectiveness analysis.

OBJECTIVE: The primary aim of this model analysis was to compare the clinical and economic impacts of immediate polypectomy versus 3-year CT colonography (CTC) surveillance for small (6- to 9-mm) polyps detected at CTC screening. MATERIALS AND METHODS: A decision analysis model was constructed incorporating the expected advanced neoplasia prevalence, frequency of measurable growth, colorectal cancer (CRC) prevalence and risk, CTC performance, and costs related to CRC screening and treatment. CRC risk was assumed to be independent of advanced adenoma size, which intentionally overestimates the risk related to small polyps. Clinical effectiveness and costs for 3-year CTC surveillance versus immediate colonoscopic polypectomy were compared for a concentrated cohort of patients with 6- to 9-mm polyps. For the CTC surveillance strategy, only cases with measurable growth (> or = 1 mm) at follow-up CTC were referred for polypectomy. RESULTS: Without any intervention, the estimated 5-year CRC death rate from 6- to 9-mm polyps in this concentrated cohort was 0.08%, which is a sevenfold decrease over the 0.56% CRC risk for the general unselected screening population. The death rate was further reduced to 0.03% with the CTC surveillance strategy and to 0.02% with immediate colonoscopy referral. However, for each additional cancer-related death prevented with immediate polypectomy versus CTC follow-up, 9,977 colonoscopy referrals would be needed, resulting in 10 additional perforations and an incremental cost-effectiveness ratio of $372,853. CONCLUSION: For patients with small (6- to 9-mm) polyps detected at CTC screening, the exclusion of large polyps (> or = 10 mm) already confers a very low risk of CRC. The high costs, additional complications, and relatively low incremental yield associated with immediate polypectomy of 6- to 9-mm polyps support the practice of 3-year CTC surveillance, which allows for selective noninvasive identification of small polyps at risk.

Computed tomographic colonography to screen for colorectal cancer, extracolonic cancer, and aortic aneurysm: model simulation with cost-effectiveness analysis.

BACKGROUND: In addition to detecting colorectal neoplasia, abdominal computed tomography (CT) with colonography technique (CTC) can also detect unsuspected extracolonic cancers and abdominal aortic aneurysms (AAA).The efficacy and cost-effectiveness of this combined abdominal CT screening strategy are unknown. METHODS: A computerized Markov model was constructed to simulate the occurrence of colorectal neoplasia, extracolonic malignant neoplasm, and AAA in a hypothetical cohort of 100,000 subjects from the United States who were 50 years of age. Simulated screening with CTC, using a 6-mm polyp size threshold for reporting, was compared with a competing model of optical colonoscopy (OC), both without and with abdominal ultrasonography for AAA detection (OC-US strategy). RESULTS: In the simulated population, CTC was the dominant screening strategy, gaining an additional 1458 and 462 life-years compared with the OC and OC-US strategies and being less costly, with a savings of $266 and $449 per person, respectively. The additional gains for CTC were largely due to a decrease in AAA-related deaths, whereas the modeled benefit from extracolonic cancer downstaging was a relatively minor factor. At sensitivity analysis, OC-US became more cost-effective only when the CTC sensitivity for large polyps dropped to 61% or when broad variations of costs were simulated, such as an increase in CTC cost from $814 to $1300 or a decrease in OC cost from $1100 to $500. With the OC-US approach, suboptimal compliance had a strong negative influence on efficacy and cost-effectiveness. The estimated mortality from CT-induced cancer was less than estimated colonoscopy-related mortality (8 vs 22 deaths), both of which were minor compared with the positive benefit from screening. CONCLUSION: When detection of extracolonic findings such as AAA and extracolonic cancer are considered in addition to colorectal neoplasia in our model simulation, CT colonography is a dominant screening strategy (ie, more clinically effective and more cost-effective) over both colonoscopy and colonoscopy with 1-time ultrasonography.

Is there sufficient MDCT capacity to provide colorectal cancer screening with CT colonography for the U.S. population?

OBJECTIVE: The impact of introducing widespread colorectal cancer (CRC) screening with CT colonography (CTC) on current resource capacity is unknown. Although a relatively large number of MDCT scanners are currently in operation throughout the United States, these existing units already perform studies for a wide array of indications. Our aim was to assess the ability of the available MDCT capacity in the United States to provide population screening with CTC. MATERIALS AND METHODS: Mathematic and Markov models were used to assess the mean number of CTC procedures per MDCT scanner per day (expressed as CTC/MDCT/day) necessary for both the startup and steady-state phases of a nationwide screening effort. Plausible ranges were applied to a number of variables in the sensitivity analysis. The number of existing CT scanners in the United States was based on 2006 estimates. RESULTS: At baseline analysis, assuming gradual increases in compliance, CTC penetrance (percentage of screening-compliant population who would opt for CTC), and MDCT capacity, a total of 37,227,541 adults would need to undergo CTC screening over a 10-year startup period, corresponding to 1.2-1.6 CTC/MDCT/day. Assuming a 5-year routine screening interval between the ages of 50 and 80 years, the number of CTC studies needed to be performed in the steady-state period is 1.2 CTC/MDCT/day. These estimates were sensitive to variations in compliance, MDCT capacity, population size, interval for the startup phase, and the routine CTC screening interval. CONCLUSION: CT capacity in the United States appears to be adequate for handling the potential demand related to mass population screening with CTC, even without assuming a specific CTC-driven increase in MDCT supply.

Small and diminutive polyps detected at screening CT colonography: a decision analysis for referral to colonoscopy.

OBJECTIVE: The objective of this study was to assess the clinical and economic impact of colonoscopic referral for small and diminutive polyps detected at CT colonography (CTC) screening. MATERIALS AND METHODS: A decision analysis model was constructed incorporating the expected polyp distribution, advanced adenoma prevalence, colorectal cancer (CRC) risk, CTC performance, and costs related to CRC screening and treatment. The model conservatively assumed that CRC risk was independent of advanced adenoma size. The number of diminutive (< or = 5 mm), small (6-9 mm), and large (> or = 10 mm) CTC-detected polyps needed to be removed to detect one advanced adenoma or prevent one CRC over a 10-year time horizon was calculated. The cost-effectiveness of polypectomy was also assessed. RESULTS: The estimated 10-year CRC risk for unresected diminutive, small, and large polyps was 0.08%, 0.7%, and 15.7%, respectively. The number of diminutive, small, and large polyps needed to be removed to avoid leaving behind one advanced adenoma was 562, 71, and 2.5, respectively; similarly, 2,352, 297, and 10.7 polypectomies would be needed, respectively, to prevent one CRC over 10 years. The incremental cost-effectiveness ratio of removing all diminutive and small CTC-detected polyps was $464,407 and $59,015 per life-year gained, respectively. Polypectomy for large CTC-detected polyps yielded a cost-saving of $151 per person screened. CONCLUSION: For diminutive polyps detected at CTC screening, the very low likelihood of advanced neoplasia and the high costs associated with polypectomy argue against colonoscopic referral, whereas removal of large CTC-detected polyps is highly effective. The yield of colonoscopic referral for small polyps is relatively low, suggesting that CTC surveillance may be a reasonable management option.