Red flags to screen for vertebral fracture in patients presenting with low-back pain.

EDITORIAL NOTE: See https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD014461.pub2/full for a more recent review that covers this topic and has superseded this review. BACKGROUND: Low-back pain (LBP) is a common condition seen in primary care. A principal aim during a clinical examination is to identify patients with a higher likelihood of underlying serious pathology, such as vertebral fracture, who may require additional investigation and specific treatment. All 'evidence-based' clinical practice guidelines recommend the use of red flags to screen for serious causes of back pain. However, it remains unclear if the diagnostic accuracy of red flags is sufficient to support this recommendation. OBJECTIVES: To assess the diagnostic accuracy of red flags obtained in a clinical history or physical examination to screen for vertebral fracture in patients presenting with LBP. SEARCH METHODS: Electronic databases were searched for primary studies between the earliest date and 7 March 2012. Forward and backward citation searching of eligible studies was also conducted. SELECTION CRITERIA: Studies were considered if they compared the results of any aspect of the history or test conducted in the physical examination of patients presenting for LBP or examination of the lumbar spine, with a reference standard (diagnostic imaging). The selection criteria were independently applied by two review authors. DATA COLLECTION AND ANALYSIS: Three review authors independently conducted 'Risk of bias' assessment and data extraction. Risk of bias was assessed using the 11-item QUADAS tool. Characteristics of studies, patients, index tests and reference standards were extracted. Where available, raw data were used to calculate sensitivity and specificity with 95% confidence intervals (CI). Due to the heterogeneity of studies and tests, statistical pooling was not appropriate and the analysis for the review was descriptive only. Likelihood ratios for each test were calculated and used as an indication of clinical usefulness. MAIN RESULTS: Eight studies set in primary (four), secondary (one) and tertiary care (accident and emergency = three) were included in the review. Overall, the risk of bias of studies was moderate with high risk of selection and verification bias the predominant flaws. Reporting of index and reference tests was poor. The prevalence of vertebral fracture in accident and emergency settings ranged from 6.5% to 11% and in primary care from 0.7% to 4.5%. There were 29 groups of index tests investigated however, only two featured in more than two studies. Descriptive analyses revealed that three red flags in primary care were potentially useful with meaningful positive likelihood ratios (LR+) but mostly imprecise estimates (significant trauma, older age, corticosteroid use; LR+ point estimate ranging 3.42 to 12.85, 3.69 to 9.39, 3.97 to 48.50 respectively). One red flag in tertiary care appeared informative (contusion/abrasion; LR+ 31.09, 95% CI 18.25 to 52.96). The results of combined tests appeared more informative than individual red flags with LR+ estimates generally greater in magnitude and precision. AUTHORS' CONCLUSIONS: The available evidence does not support the use of many red flags to specifically screen for vertebral fracture in patients presenting for LBP. Based on evidence from single studies, few individual red flags appear informative as most have poor diagnostic accuracy as indicated by imprecise estimates of likelihood ratios. When combinations of red flags were used the performance appeared to improve. From the limited evidence, the findings give rise to a weak recommendation that a combination of a small subset of red flags may be useful to screen for vertebral fracture. It should also be noted that many red flags have high false positive rates; and if acted upon uncritically there would be consequences for the cost of management and outcomes of patients with LBP. Further research should focus on appropriate sets of red flags and adequate reporting of both index and reference tests.

Correction to: Estimation of treatment preference effects in clinical trials when some participants are indifferent to treatment choice.

In the original publication of this article [1], the number "- 0.49" in the below sentence in the Results section should be changed to "-3.23", and this typo does not affect the wider conclusions.

Should heart age calculators be used alongside absolute cardiovascular disease risk assessment?

BACKGROUND: National estimates of 'heart age' by government health organisations in the US, UK and China show most people have an older heart age than current age. While most heart age calculators are promoted as a communication tool for lifestyle change, they may also be used to justify medication when clinical guidelines advocate their use alongside absolute risk assessment. However, only those at high absolute risk of a heart attack or stroke are likely to benefit from medication, and it is not always clear how heart age relates to absolute risk. This article aims to: 1) explain how heart age calculation methods relate to absolute risk guidelines; 2) summarise research investigating whether heart age improves risk communication; and 3) discuss implications for the use of medication and shared decision making in clinical practice. MAIN BODY: There is a large and growing number of heart age models and online calculators, but the clinical meaning of an older heart age result is highly variable. An older heart age result may indicate low, moderate or high absolute risk of a heart attack or stroke in the next 5-10 years, and the same individual may receive a younger or older heart age result depending on which calculator is used. Heart age may help doctors convey the need to change lifestyle, but it cannot help patients make an informed choice about medication to reduce CVD risk. CONCLUSION: Interactive heart age tools may be helpful as a communication tool to initiate lifestyle change to reduce risk factors. However, absolute risk should be used instead of heart age to enable informed decision making about medication, to avoid unnecessary treatment of low risk people. Evidence-based decision aids that improve patient understanding of absolute risk should be considered as alternatives to heart age calculators for lifestyle and medication decisions.

Use of shared care and routine tests in follow-up after treatment for localised cutaneous melanoma.

BACKGROUND: Patients may decide to undertake shared care with a general practitioner (GP) during follow-up after treatment for localised melanoma. Routine imaging tests for surveillance may be commonly used despite no evidence of clinical utility. This study describes the frequency of shared care and routine tests during follow-up after treatment for localised melanoma. METHODS: We randomly sampled 351 people with localised melanoma [American Joint Cancer Committee (AJCC) substages 0 - II] who had not had recurrent or new primary melanoma diagnosed from a total of 902 people diagnosed and treated for localised melanoma at a specialist centre in 2014. We interviewed participants by telephone about their experience of follow-up in the past year, and documented the proportion of patients who were undertaking shared care follow-up with a GP. We also recorded the frequency and type of investigations during follow-up. We calculated weighted estimates that are representative of the full inception cohort. RESULTS: Of the 351 people who were invited to participate, 230 (66%) people consented to the telephone interview. The majority undertook shared care follow-up with a GP (61%). People who choose to have shared care follow-up with a GP are more likely to be male (p = 0.006), have lower AJCC stage (p for trend = 0.02), reside in more remote areas (p for trend< 0.001), and are less likely to have completed secondary school (p < 0.001). Few people saw a non-doctor health practitioner as part of their follow-up (9%). Many people report undergoing tests for melanoma, much of which may be routine tests for surveillance (37%). CONCLUSIONS: The majority of people treated for a first primary localised melanoma at a specialist centre, without recurrent or new melanoma, choose to undertake shared care follow-up with a GP. Many appear to have routine diagnostic imaging as part of their melanoma surveillance.

Impact of extending screening mammography to older women: Information to support informed choices.

From 2013 through 2017, the Australian national breast cancer screening programme is gradually inviting women aged 70-74 years to attend screening, following a policy decision to extend invitations to older women. We estimate the benefits and harms of the new package of biennial screening from age 50-74 compared with the previous programme of screening from age 50-69. Using a Markov model, we applied estimates of the relative risk reduction for breast cancer mortality and the risk of overdiagnosis from the Independent UK Panel on Breast Cancer Screening review to Australian breast cancer incidence and mortality data. We estimated screening specific outcomes (recalls for further imaging, biopsies, false positives, and interval cancer rates) from data published by BreastScreen Australia. When compared with stopping at age 69, screening 1,000 women to age 74 is likely to avert one more breast cancer death, with an additional 78 women receiving a false positive result and another 28 women diagnosed with breast cancer, of whom eight will be overdiagnosed and overtreated. The extra 5 years of screening results in approximately 7 more overdiagnosed cancers to avert one more breast cancer death. Thus extending screening mammography in Australia to older women results in a less favourable harm to benefit ratio than stopping at age 69. Supporting informed decision making for this age group should be a public health priority.

Trends in stage-specific breast cancer incidence in New South Wales, Australia: insights into the effects of 25 years of screening mammography.

PURPOSE: Screening mammography aims to improve breast cancer (BC) prognosis by increasing the incidence of early-stage tumours in order to decrease the incidence of late-stage cancer, but no reports have investigated these potential effects in an Australian population. Therefore we aimed to identify temporal trends in stage-specific BC in New South Wales (NSW), Australia, between 1972 and 2012. METHODS: An observational study of women who received a diagnosis of BC from 1972-2012 as recorded in the NSW Cancer Registry, a population-based registry with almost complete coverage and high rates of histological verification. We analysed trends in stage-specific incidence before screening and compared them to periods after screening began. Our primary group of interest was women in the target age range of 50-69 years, though trends in women outside the target age were also assessed. RESULTS: Screening was not associated with lower incidence of late-stage BC at diagnosis. Incidence for all stages remained higher than prescreening levels. In women aged 50-69 years, the incidence of carcinoma in situ (CIS), localised and regional BC has more than doubled compared to the prescreening era, with incidence rate ratios ranging from 2.0 for regional (95% CI 1.95-2.13) to 121.8 for CIS (95% CI 82.58-179.72). Before the introduction of screening, there was a downward trend in distant metastatic BC incidence, and after the introduction of screening there was an increase (IRR 1.8; 95% CI 1.62-2.00). In women too young to screen the incidence of late-stage BC at diagnosis also increased, whereas localised disease was stable. CONCLUSIONS: The incidence of all stages of BC has increased over the past 40 years, with the greatest rise seen during the established screening period for women aged 50-69 years. Our findings suggest that some of the expected benefits of screening may not have been realised and are consistent with overdiagnosis.

Fear of new or recurrent melanoma after treatment for localised melanoma.

OBJECTIVE: To estimate the amount of fear of new or recurrent melanoma among people treated for localised melanoma in an Australian specialist centre. METHODS: We randomly selected 400 potential participants from all those treated for localised melanoma at the Melanoma Institute Australia during 2014 (n = 902). They were asked to complete an adapted version of the Fear of Cancer Recurrence Inventory (FCRI). We calculated summary statistics for demographics, clinical variables and total FCRI and subscale scores. RESULTS: Two hundred fifteen people (54%) completed the FCRI questionnaire. The overall mean severity subscale score was 15.0 (95% CI 14.0-16.1). A high proportion of participants had scores above a proposed threshold to screen for clinical fear of cancer recurrence (77% and 63% of participants with and without new or recurrent melanoma had severity subscale scores ≥13). Most participants also had scores above a threshold found to have high specificity for clinical fear of cancer recurrence (65% and 48% of participants with and without new or recurrent melanoma had severity subscale scores ≥16). The severity subscale appeared to discriminate well between groups with differing levels of risk of new or recurrent melanoma. CONCLUSIONS: There is a substantial amount of fear of new or recurrent melanoma among this population, despite most having a very good prognosis.

Estimation of treatment preference effects in clinical trials when some participants are indifferent to treatment choice.

BACKGROUND: In the two-stage randomised trial design, a randomly sampled subset of study participants are permitted to choose their own treatment, while the remaining participants are randomised to treatment in the usual way. Appropriate analysis of the data from both arms of the study allows investigators to estimate the impact on study outcomes of treatment preferences that patients may have, in addition to evaluating the usual direct effect of treatment. In earlier work, we showed how to optimise this design by making a suitable choice of the proportion of participants who should be assigned to the choice arm of the trial. However, we ignored the possibility of some participants being indifferent to the treatments under study. In this paper, we extend our earlier work to consider the analysis of two-stage randomised trials when some participants have no treatment preference, even if they are assigned to the choice arm and allowed to choose. METHODS: We compare alternative characterisations of the response profiles of the indifferent or undecided participants, and derive estimates of the treatment and preference effects on study outcomes. We also present corresponding test statistics for these parameters. The methods are illustrated with data from a clinical trial contrasting medical and surgical interventions. RESULTS: Expressions are obtained to estimate and test the impact of treatment choices on study outcomes, as well as the impact of the actual treatment received. Contrasts are defined between patients with stated treatment preferences and those with no preference. Alternative assumptions concerning the outcomes of undecided participants are described, and an approach leading to unbiased estimation and testing is identified. CONCLUSIONS: Use of the two-stage design can provide important insights into determinants of study outcomes that are not identifiable with other designs. The design can remain attractive even in the presence of participants with no stated treatment preference.

EARLY CRT MONITORING USING TIME-DOMAIN OPTICAL COHERENCE TOMOGRAPHY DOES NOT ADD TO VISUAL ACUITY FOR PREDICTING VISUAL LOSS IN PATIENTS WITH CENTRAL RETINAL VEIN OCCLUSION TREATED WITH INTRAVITREAL RANIBIZUMAB: A Secondary Analysis of Trial Data.

PURPOSE: Our primary purpose was to assess the clinical (predictive) validity of central retinal thickness (CRT) and best corrected visual acuity (BCVA) at 1 week and 1 month after starting treatment with ranibizumab for central retinal vein occlusion. The authors also assessed detectability of response to treatment. METHODS: The authors used data from 325 participants in the CRUISE study, which included measurement of time-domain CRT and BCVA at baseline, 1 week, 1 month, and 6 months postrandomization. Analysis of covariance models were fitted to assess clinical validity, and distributions of change were constructed to assess detectability of response. RESULTS: There was no evidence that 1-week CRT, and very strong evidence that 1-week BCVA were associated with baseline-adjusted BCVA at 6 months (P = 0.17 and P < 0.001, respectively). There was strong evidence that both 1-month CRT and 1-month BCVA were associated with baseline-adjusted 6-month BCVA (P = 0.005 and P < 0.001, respectively), but simultaneous adjustment found evidence of independent association only for BCVA (P = 0.71 and P < 0.001 for CRT and BCVA, respectively). Detectability of response tended to be higher for CRT than BCVA at 1 week and 1 month but by 6 months these were equivalent for CRT and BCVA. CONCLUSION: In this study, BCVA monitoring of treated central retinal vein occlusion patients seemed more informative than time-domain optical coherence tomography monitoring.

Use of a decision aid including information on overdetection to support informed choice about breast cancer screening: a randomised controlled trial.

BACKGROUND: Mammography screening can reduce breast cancer mortality. However, most women are unaware that inconsequential disease can also be detected by screening, leading to overdiagnosis and overtreatment. We aimed to investigate whether including information about overdetection of breast cancer in a decision aid would help women aged around 50 years to make an informed choice about breast screening. METHODS: We did a community-based, parallel-group, randomised controlled trial in New South Wales, Australia, using a random cohort of women aged 48-50 years. Recruitment to the study was done by telephone; women were eligible if they had not had mammography in the past 2 years and did not have a personal or strong family history of breast cancer. With a computer program, we randomly assigned 879 participants to either the intervention decision aid (comprising evidence-based explanatory and quantitative information on overdetection, breast cancer mortality reduction, and false positives) or a control decision aid (including information on breast cancer mortality reduction and false positives). Participants and interviewers were masked to group assignment. The primary outcome was informed choice (defined as adequate knowledge and consistency between attitudes and screening intentions), which we assessed by telephone interview about 3 weeks after random allocation. The primary outcome was analysed in all women who completed the relevant follow-up interview questions fully. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12613001035718. FINDINGS: Between January, 2014, and July, 2014, 440 women were allocated to the intervention group and 439 were assigned to the control group. 21 women in the intervention group and 20 controls were lost to follow-up; a further ten women assigned to the intervention and 11 controls did not answer all questions on attitudes. Therefore, 409 women in the intervention group and 408 controls were analysed for the primary outcome. 99 (24%) of 409 women in the intervention group made an informed choice compared with 63 (15%) of 408 in the control group (difference 9%, 95% CI 3-14; p=0·0017). Compared with controls, more women in the intervention group met the threshold for adequate overall knowledge (122/419 [29%] vs 71/419 [17%]; difference 12%, 95% CI 6-18; p<0·0001), fewer women expressed positive attitudes towards screening (282/409 [69%] vs 340/408 [83%]; 14%, 9-20; p<0·0001), and fewer women intended to be screened (308/419 [74%] vs 363/419 [87%]; 13%, 8-19; p<0·0001). When conceptual knowledge alone was considered, 203 (50%) of 409 women in the intervention group made an informed choice compared with 79 (19%) of 408 in the control group (p<0·0001). INTERPRETATION: Information on overdetection of breast cancer provided within a decision aid increased the number of women making an informed choice about breast screening. Becoming better informed might mean women are less likely to choose screening. FUNDING: Australian National Health and Medical Research Council.

The Association of Surgical Margins and Local Recurrence in Women with Ductal Carcinoma In Situ Treated with Breast-Conserving Therapy: A Meta-Analysis.

PURPOSE: There is no consensus on adequate negative margins in breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). We systematically reviewed the evidence on margins in BCS for DCIS. METHODS: A study-level meta-analysis of local recurrence (LR), microscopic margin status and threshold distance for negative margins. LR proportion was modeled using random-effects logistic meta-regression (frequentist) and network meta-analysis (Bayesian) that allows for multiple margin distances per study, adjusting for follow-up time. RESULTS: Based on 20 studies (LR: 865 of 7883), odds of LR were associated with margin status [logistic: odds ratio (OR) 0.53 for negative vs. positive/close (p < 0.001); network: OR 0.45 for negative vs. positive]. In logistic meta-regression, relative to >0 or 1 mm, ORs for 2 mm (0.51), 3 or 5 mm (0.42) and 10 mm (0.60) showed comparable significant reductions in the odds of LR. In the network analysis, ORs relative to positive margins for 2 (0.32), 3 (0.30) and 10 mm (0.32) showed similar reductions in the odds of LR that were greater than for >0 or 1 mm (0.45). There was weak evidence of lower odds at 2 mm compared with >0 or 1 mm [relative OR (ROR) 0.72, 95 % credible interval (CrI) 0.47-1.08], and no evidence of a difference between 2 and 10 mm (ROR 0.99, 95 % CrI 0.61-1.64). Adjustment for covariates, and analyses based only on studies using whole-breast radiotherapy, did not change the findings. CONCLUSION: Negative margins in BCS for DCIS reduce the odds of LR; however, minimum margin distances above 2 mm are not significantly associated with further reduced odds of LR in women receiving radiation.

Factors influencing general practitioners' decisions about cardiovascular disease risk reassessment: findings from experimental and interview studies.

BACKGROUND: Guidelines on cardiovascular disease (CVD) risk reassessment intervals are unclear, potentially leading to detrimental practice variation: too frequent can result in overtreatment and greater strain on the healthcare system; too infrequent could result in the neglect of high risk patients who require medication. This study aimed to understand the different factors that general practitioners (GPs) consider when deciding on the reassessment interval for patients previously assessed for primary CVD risk. METHODS: This paper combines quantitative and qualitative data regarding reassessment intervals from two separate studies of CVD risk management. Experimental study: 144 Australian GPs viewed a random selection of hypothetical cases via a paper-based questionnaire, in which blood pressure, cholesterol and 5-year absolute risk (AR) were systematically varied to appear lower or higher. GPs were asked how they would manage each case, including an open-ended response for when they would reassess the patient. Interview study: Semi-structured interviews were conducted with a purposive sample of 25 Australian GPs, recruited separately from the GPs in the experimental study. Transcribed audio-recordings were thematically coded, using the Framework Analysis method. EXPERIMENT: GPs stated that they would reassess the majority of patients across all absolute risk categories in 6 months or less (low AR = 52 % [CI95% = 47-57 %], moderate AR = 82 % [CI95% = 76-86 %], high AR = 87 % [CI95% = 82-90 %], total = 71 % [CI95% = 67-75 %]), with 48 % (CI95% = 43-53 %) of patients reassessed in under 3 months. The majority (75 % [CI95% = 70-79 %]) of patients with low-moderate AR (≤15 %) and an elevated risk factor would be reassessed in under 6 months. Interviews: GPs identified different functions for reassessment and risk factor monitoring, which affected recommended intervals. These included perceived psychosocial benefits to patients, preparing the patient for medication, and identifying barriers to lifestyle change and medication adherence. Reassessment and monitoring intervals were driven by patient motivation to change lifestyle, patient demand, individual risk factors, and GP attitudes. CONCLUSIONS: There is substantial variation in reassessment intervals for patients with the same risk profile. This suggests that GPs are not following reassessment recommendations in the Australian guidelines. The use of shorter intervals for low-moderate AR contradicts research on optimal monitoring intervals, and may result in unnecessary costs and over-treatment.

Accuracy of ultrasound for predicting pathologic response during neoadjuvant therapy for breast cancer.

Early assessment of response to neoadjuvant chemotherapy (NAC) for breast cancer allows therapy to be tailored; however, optimal response assessment methods have not been established. We estimated the accuracy of ultrasound (US) to predict pathologic complete response (pCR) using common response criteria and pCR definitions, and estimated incremental accuracy over known prognostic variables. Participants undergoing US after two cycles in the GeparTrio trial randomised to no change in NAC were eligible. US response by World Health Organisation (WHO) criteria (1D or 2D) and Response Evaluation Criteria In Solid Tumours (RECIST) was assessed. Four pCR definitions were applied. Sensitivity (correct prediction of pCR), specificity (correct prediction of no-pCR) and diagnostic odds ratios (DORs) were calculated. Areas under the curve (AUCs) were derived from logistic regression including patient variables with and without US. In 832 patients, DORs decreased as pCR definitions became less stringent (p = 0.01). For WHO-2D, DORs were as follows: 4.07 (ypT0,ypN0), 3.75 (ypT0/is,ypN0), 3.14 (ypT0/is,ypN+/-) and 2.65 (ypT0/is/1a,ypN+/-). DORs did not differ between US criteria (p = 0.60). High sensitivity and lower specificity were found for WHO-2D and RECIST; WHO-1D was highly specific with low sensitivity. Sensitivity was highest for WHO-2D predicting ypT0,ypN0 (sensitivity = 81.7%, specificity = 47.6% vs. 42.3% and 80.4% for WHO-1D). Adding US to models including patient variables (age, T-stage, histology and subtype) improved AUCs for predicting pCR by 2-3%. In conclusion, US accuracy is highest for predicting ypT0,ypN0, shown to be most prognostic of long-term survival. WHO-2D and RECIST maximise sensitivity; WHO-1D maximises specificity. US modestly improves the prediction of pCR by patient characteristics.

STARD 2015: An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies.

Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies.

STARD 2015: An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies.

Incomplete reporting has been identified as a major source of avoidable waste in biomedical research. Essential information is often not provided in study reports, impeding the identification, critical appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy studies, the Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement was developed. Here we present STARD 2015, an updated list of 30 essential items that should be included in every report of a diagnostic accuracy study. This update incorporates recent evidence about sources of bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such, STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy studies.

How Often Do Patients with Localized Melanoma Attend Follow-Up at a Specialist Center?

BACKGROUND: Post-treatment follow-up for patients with American Joint Committee on Cancer (AJCC) stage I/II melanoma is believed to be important for early detection of disease recurrence and new primary melanomas, but comes with costs to both patients and healthcare providers. We aimed to determine how frequently a cohort of patients attended follow-up after surgical treatment at one Specialist Center. METHODS: We used prospectively collected data from the Melanoma Institute Australia (MIA) for patients with AJCC stage I/II melanoma diagnosed between January 2008 and December 2011. The distribution of the number of recorded follow-up visits per patient was analyzed and compared with the number of follow-up visits recommended in the 2008 Australian and New Zealand Melanoma Management Guidelines. RESULTS: A total of 3813 patients with stage I/II melanoma were identified. During the first year of follow-up post-surgery, 34 % of stage I patients and 14 % of stage II patients had the number of follow-up visits recommended in the guidelines. A large proportion of melanoma patients did not appear to be routinely followed up at MIA, with 43.2 % of stage I patients and 28.7 % of stage II patients having either no visit or only one visit post-surgery. During all years of follow-up, 13.2 % of stage I patients and 4.1 % of stage II patients had the number of follow-up visits at the specialist center as recommended in the guidelines. CONCLUSIONS: The large proportion of patients who had fewer follow-up visits than expected suggests (i) many patients are followed up in clinics elsewhere, and/or (ii) post-surgical surveillance is less frequent in practice.

Agreement between MRI and pathologic breast tumor size after neoadjuvant chemotherapy, and comparison with alternative tests: individual patient data meta-analysis.

BACKGROUND: Magnetic resonance imaging (MRI) may guide breast cancer surgery by measuring residual tumor size post-neoadjuvant chemotherapy (NAC). Accurate measurement may avoid overly radical surgery or reduce the need for repeat surgery. This individual patient data (IPD) meta-analysis examines MRI's agreement with pathology in measuring the longest tumor diameter and compares MRI with alternative tests. METHODS: A systematic review of MEDLINE, EMBASE, PREMEDLINE, Database of Abstracts of Reviews of Effects, Heath Technology Assessment, and Cochrane databases identified eligible studies. Primary study authors supplied IPD in a template format constructed a priori. Mean differences (MDs) between tests and pathology (i.e. systematic bias) were calculated and pooled by the inverse variance method; limits of agreement (LOA) were estimated. Test measurements of 0.0 cm in the presence of pathologic residual tumor, and measurements >0.0 cm despite pathologic complete response (pCR) were described for MRI and alternative tests. RESULTS: Eight studies contributed IPD (N = 300). The pooled MD for MRI was 0.0 cm (LOA: +/-3.8 cm). Ultrasound underestimated pathologic size (MD: -0.3 cm) relative to MRI (MD: 0.1 cm), with comparable LOA. MDs were similar for MRI (0.1 cm) and mammography (0.0 cm), with wider LOA for mammography. Clinical examination underestimated size (MD: -0.8 cm) relative to MRI (MD: 0.0 cm), with wider LOA. Tumors "missed" by MRI typically measured 2.0 cm or less at pathology; tumors >2.0 cm were more commonly "missed" by clinical examination (9.3 %). MRI measurements >5.0 cm occurred in 5.3 % of patients with pCR, but were more frequent for mammography (46.2 %). CONCLUSIONS: There was no systematic bias in MRI tumor measurement, but LOA are large enough to be clinically important. MRI's performance was generally superior to ultrasound, mammography, and clinical examination, and it may be considered the most appropriate test in this setting. Test combinations should be explored in future studies.