Evidence-informed recommendations on managing breast screening atypia: perspectives from an expert panel consensus meeting reviewing results from the Sloane atypia project.

Evidence-based clinical guidelines are essential to maximize patient benefit and to reduce clinical uncertainty and inconsistency in clinical practice. Gaps in the evidence base can be addressed by data acquired in routine practice. At present, there is no international consensus on management of women diagnosed with atypical lesions in breast screening programmes. Here, we describe how routine NHS breast screening data collected by the Sloane atypia project was used to inform a management pathway that maximizes early detection of cancer and minimizes over-investigation of lesions with uncertain malignant potential. A half-day consensus meeting with 11 clinical experts, 1 representative from Independent Cancer Patients' Voice, 6 representatives from NHS England (NHSE) including from Commissioning, and 2 researchers was held to facilitate discussions of findings from an analysis of the Sloane atypia project. Key considerations of the expert group in terms of the management of women with screen detected atypia were: (1) frequency and purpose of follow-up; (2) communication to patients; (3) generalizability of study results; and (4) workforce challenges. The group concurred that the new evidence does not support annual surveillance mammography for women with atypia, irrespective of type of lesion, or woman's age. Continued data collection is paramount to monitor and audit the change in recommendations.

The first clinical implementation of real-time 6 degree-of-freedom image-guided radiotherapy for liver SABR patients.

PURPOSE: Multiple survey results have identified a demand for improved motion management for liver cancer IGRT. Until now, real-time IGRT for liver has been the domain of dedicated and expensive cancer radiotherapy systems. The purpose of this study was to clinically implement and characterise the performance of a novel real-time 6 degree-of-freedom (DoF) IGRT system, Kilovoltage Intrafraction Monitoring (KIM) for liver SABR patients. METHODS/MATERIALS: The KIM technology segmented gold fiducial markers in intra-fraction x-ray images as a surrogate for the liver tumour and converted the 2D segmented marker positions into a real-time 6DoF tumour position. Fifteen liver SABR patients were recruited and treated with KIM combined with external surrogate guidance at three radiotherapy centres in the TROG 17.03 LARK multi-institutional prospective clinical trial. Patients were either treated in breath-hold or in free breathing using the gating method. The KIM localisation accuracy and dosimetric accuracy achieved with KIM + external surrogate were measured and the results were compared to those with the estimated external surrogate alone. RESULTS: The KIM localisation accuracy was 0.2±0.9 mm (left-right), 0.3±0.6 mm (superior-inferior) and 1.2±0.8 mm (anterior-posterior) for translations and -0.1◦±0.8◦ (left-right), 0.6◦±1.2◦ (superior-inferior) and 0.1◦±0.9◦ (anterior-posterior) for rotations. The cumulative dose to the GTV with KIM + external surrogate was always within 5% of the plan. In 2 out of 15 patients, >5% dose error would have occurred to the GTV and an organ-at-risk with external surrogate alone. CONCLUSIONS: This work demonstrates that real-time 6DoF IGRT for liver can be implemented on standard radiotherapy systems to improve treatment accuracy and safety. The observations made during the treatments highlight the potential false assurance of using traditional external surrogates to assess tumour motion in patients and the need for ongoing improvement of IGRT technologies.

Improving plan quality in cervical brachytherapy using a simple knowledge-based prediction tool for OAR dose (D2cm3).

PURPOSE: Toxicity from cervical brachytherapy has been demonstrated to correlate with the D2cm3 of the bladder, rectum, and bowel. This suggests a simplified version of knowledge-based planning investigating the relationship of the overlap distance for 2cm3 and the D2cm3 from planning may be possible. This work demonstrates the feasibility of simple knowledge-based planning to predict the D2cm3, detect suboptimal plans, and improve plan quality. METHODS AND MATERIALS: The overlap volume histogram (OVH) method was used to determine the distance for 2cm3 of overlap between the OAR and CTV_HR. Linear plots modeled the OAR D2cm3 and 2cm3 overlap distance. Two datasets of 20 patients (plans from 43 insertions in each dataset) were used to create two independent models, and the performance of each model was compared using cross-validation. Doses were scaled to ensure consistent CTV_HR D90 values. The predicted D2cm3 is entered as the maximum constraint in the inverse planning algorithm. RESULTS: Mean bladder D2cm3 decreased by 2.9% for the models from each dataset, mean rectal D2cm3 decreased 14.9% for the model from dataset 1 and 6.0% for the model from dataset 2, mean sigmoid D2cm3 decreased 10.7% for the model from dataset 1 and 6.1% for the model from dataset 2, mean bowel D2cm3 decreased 4.1% for the model from dataset 1 but no statistically significant difference was observed for the model from dataset 2. CONCLUSIONS: A simplified knowledge-based planning method was used to predict D2cm3 and was able to automate optimization of brachytherapy plans for locally advanced cervical cancer.

Pain and Fatigue in Patients With Ankylosing Spondylitis Treated With Tumor Necrosis Factor Inhibitors: Multinational Real-World Findings.

BACKGROUND/OBJECTIVE: Patients with ankylosing spondylitis (AS) experience symptoms and comorbidities that impact their health-related quality of life (HRQoL) and ability to work. This real-world, global survey was conducted among AS patients receiving tumor necrosis factor inhibitors (TNFis) to evaluate both the frequency and severity of persistent symptoms, and the impact of pain and fatigue on HRQoL, employment status, and work activity. METHODS: Patients with AS and their treating physicians from 13 countries across 5 continents completed questionnaires capturing demographics, patient symptoms, current disease status, HRQoL, current therapy, employment status, and Work Productivity and Activity Impairment. RESULTS: Seven hundred five patients who had been receiving a TNFi for 3 months or more and completed both Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) pain and fatigue domains were included in the analysis; of these, 37.6% reported high BASDAI pain scores and 41.3% high BASDAI fatigue scores. Medical Outcomes Study-Short Form, 36-item version 2 domain, 5-dimensional EuroQoL Questionnaire, and 5-dimensional EuroQoL visual analog scale scores were significantly lower (p < 0.0001), and Work Productivity and Activity Impairment scores significantly higher (p < 0.0001), in patients with high levels of pain or fatigue than low levels. CONCLUSIONS: Globally, levels of pain and fatigue remained high in AS patients receiving TNFi treatment, which were significantly associated with reduced HRQoL and work productivity. Such persistent symptoms in usual care suggest a substantial unmet need in AS pharmacologic and nonpharmacologic therapeutic pathways.

A single-institution review of image-guided brachytherapy for vaginal malignancies using customized molded applicators and interstitial needles.

PURPOSE: To review a single-institution's pattern of practice, dosimetry results, and clinical outcomes for patients with unresectable malignancies of vagina, vulva, or urethra, receiving brachytherapy using customized vaginal moulds with or without interstitial needles. MATERIAL AND METHODS: Twenty-one consecutive patients were reviewed. Patients were treated using customized moulds with or without interstitial needles, implanted with a free-hand technique. Technical implementation, such as type of implant and imaging used were recorded. D90 and D98 of clinical target volume (CTV), D0.1cc of urethra, and D2cc and D0.1cc of bladder and rectum were analyzed. Any adverse clinical outcomes were reported. RESULTS: Eleven patients experienced endometrial cancer recurrences, one a cervical cancer recurrence and nine vaginal or peri-urethral primary disease. After a median follow-up of 3.5 years, local control was achieved in 14 patients (67%). Median D98 and D90 to CTV was 73.7 Gy and 78.3 Gy, respectively. One patient died from disease progression, one developed distant metastasis, and seven failed locally. Median D2cc to bladder was 64.8 Gy, with low-grade toxicity reported. Median D2cc to rectum was 62.9 Gy, with low-grade toxicity and one case of rectal proctitis was observed. Median urethral D0.1cc was 66 Gy, with no toxicity reported. One patient suffered from a sacral insufficiency fracture. It was presumed that vaginal mucosa proximal to CTV received the total dose, with two patients developing vaginal ulcers, which both resolved; 10 patients reported mild telangiectasia, fibrosis, or stenosis. CONCLUSIONS: A review of patients treated with a customized vaginal mould and interstitial needles showed acceptable doses to CTV, with local control achieved in 67% of patients, and reasonable doses to organs at risk (OARs) and acceptable toxicity.

Relationship of pain and fatigue with health-related quality of life and work in patients with psoriatic arthritis on TNFi: results of a multi-national real-world study.

BACKGROUND/OBJECTIVE: The incidence of pain and/or fatigue in people with psoriatic arthritis (PsA) is associated with reduced health-related quality of life (HRQoL) and the ability to work, despite modern advanced therapeutic approaches. This real-world, international study examined these relationships in patients with PsA treated with tumour necrosis factor inhibitors (TNFi). METHODS: Data from 13 countries were analysed. Patients with PsA and their physicians completed questionnaires capturing demographics, current therapy, current disease status, HRQoL and work status via Medical Outcomes Study 36-Item Short-Form version 2 (SF-36v2), 3-level 5-dimension EuroQoL questionnaire, Health Assessment Questionnaire Disability Index, and Work Productivity and Activity Impairment (WPAI) questionnaire. RESULTS: 640 patients with PsA were included who had been receiving TNFi for ≥3 months and had completed SF-36v2 bodily pain and vitality domains. Of these, 33.1%, 29.2% and 37.7% of patients reported no, moderate and severe pain, respectively, and 31.9%, 22.5% and 45.6% of patients reported low, moderate and severe fatigue, respectively. Scores across HRQoL variables and WPAI were significantly different across pain and fatigue cohorts (all p<0.0001), with HRQoL and WPAI measures considerably worse in patients with moderate to severe pain or fatigue than those with low pain or fatigue. CONCLUSIONS: Despite treatment with biologic agents such as TNFi, data from this global study demonstrated that substantial pain and/or fatigue persist in patients with PsA and that these are significantly associated with reduced HRQoL, physical function and work productivity. These findings suggest that there is an unmet need for additional PsA therapies.

Biologic Disease-Modifying Antirheumatic Drug Prescription Patterns Among Rheumatologists in Europe and Japan.

INTRODUCTION: Tumor necrosis factor inhibitors (TNFi) are commonly used as first-line therapy (biologic disease-modifying antirheumatic drug [bDMARD] and targeted synthetic DMARD [tsDMARD]: defined as targeted therapy) for patients with moderate-to-severe rheumatoid arthritis (RA), usually combined with conventional synthetic DMARDs (csDMARDs) but sometimes as monotherapy. If treatment fails, patients cycle to another TNFi (cycling) or switch to a targeted therapy with a different mode of action (MOA; switching). The study aimed to examine prescribing patterns and reasons for current RA treatment practice in Europe (EU5: France, Germany, Italy, Spain, UK) and Japan. METHODS: Data were collected from the Adelphi Disease Specific Programme™ (DSP; Q1-Q2 2017). Rheumatologists seeing ≥ 10 (EU5) and ≥ 5 (Japan) patients with RA a month completed Patient Record Forms. Patients ≥ 18 years old, with RA diagnosis and complete RA-targeted therapy history were included. Patients were grouped based on first-line targeted therapy class, and on whether first-line targeted therapy was monotherapy (targeted therapy alone) or combination therapy (targeted therapy and csDMARD). Those patients receiving TNFi at first-line and with ≥ 1 targeted therapy were classified as TNFi cyclers or MOA switchers. Univariate analysis compared factors across groups. Patient demographics and characteristics compared across groups; physician reasoning for targeted therapy change; and time to discontinuation of targeted therapy. RESULTS: In EU5 and Japan, respectively, 1741 and 147 patients were included; at first-line, 80.8% and 64.6% received TNFi and 76.0% and 77.6% received combination therapy. Overall in EU5, more combination therapy than monotherapy patients reached maximum csDMARD dose before first-line targeted therapy (P < 0.05); disease severity was higher in patients initiating TNFi versus non-TNFi (P < 0.05). In Japan, trends were similar but not significant. The most common reason physicians gave for changing therapy following first-line targeted therapy was 'secondary lack of efficacy' (EU5: 46.2%; Japan: 53.8%). In EU5 and Japan, respectively, of 365 and 22 patients who received second-line targeted therapy, 52.1% and 54.5% were MOA switchers. In EU5, TNFi cyclers had longer time from diagnosis to second-line targeted therapy initiation than MOA switchers (P = 0.04). CONCLUSIONS: TNFis were the most commonly prescribed targeted therapy at first-line. Between 10 and 20% of patients prescribed a TNFi as first-line targeted therapy did so without concomitant csDMARD. Almost half of patients cycled to another TNFi at second-line.

Biologic Disease-Modifying Antirheumatic Drug Prescription Patterns for Rheumatoid Arthritis Among United States Physicians.

INTRODUCTION: Some patients with rheumatoid arthritis (RA) using tumor necrosis factor inhibitors (TNFi) experience inefficacy or lack of tolerability and hence switch to another TNFi (cycling) or to a therapy with another mode of action (switching). This study examined patient characteristics, prescribing patterns and treatment practice for RA in the United States. METHODS: Data were from the Adelphi Disease Specific Programme (Q2-Q3 2016). Rheumatologists completed a survey and patient record forms for adult patients with RA who had received ≥ 1 targeted therapy. Patients were grouped by class of first-used targeted therapy, and monotherapy vs. combination therapy. TNFi patients who received ≥ 1 targeted therapy were classified as cyclers or switchers. Univariate analyses compared patient characteristics and physician factors across the analysis groups. RESULTS: Overall, 631 patients received ≥ 1 targeted therapy; 535 were prescribed a TNFi as first targeted therapy, 53 a nonTNFi biologic disease-modifying antirheumatic drug (bDMARD), and 43 tofacitinib. Of 577 patients with known conventional synthetic (cs) DMARD status, 18.7% were prescribed monotherapy and 81.3% combination therapy. Combination therapy patients received significantly more concomitant medications prior to initiation of first targeted therapy than monotherapy patients (P < 0.05). The top reason for physicians to prescribe first use targeted therapy was strong overall efficacy (79.9%). Of 163 patients who progressed to second targeted therapy, 60.7% were cyclers. A lower proportion of cyclers persisted on their first use targeted therapy versus switchers (P = 0.03). The main reason physicians gave for switching patients at this stage was worsening condition (46.6%). CONCLUSIONS: Most patients were prescribed a TNFi as their first targeted therapy; over half then cycled to another TNFi. This suggests other factors may influence second use targeted treatment choice and highlights the need for greater understanding of outcomes associated with subsequent treatment choices and potential benefits of switching.

Pharmacological challenges examining the underlying mechanism of altered response inhibition and attention due to circadian disruption in adult Long-Evans rats.

Endogenous circadian rhythms govern behavior and physiology, while circadian disruption is an environmental factor that impacts cognition by altering the circadian clock at a molecular level. We modeled the effects of 2 sources of circadian disruption - activity occurring during typical rest periods and untimely light exposure - to evaluate the effects of circadian disruption on behavior and underlying neurochemistry. Firstly, adult Long-Evans rats of both sexes were maintained on a 12 h:12 h light:dark cycle and tested using a 5-choice serial reaction time task (5-CSRTT) under 3 conditions: 4 h into the dark phase with no exposure to ambient light during testing (control), 4 h into the dark phase with exposure to ambient light during testing, and 4 h into the light phase. Both models resulted in impulsive behavior and reduced attention compared to control. We established that changes in the diurnal expression pattern occur in the clock gene Period 2 (Per2) in the light phase-tested model. Choline acetyltransferase (Chat) and Dopamine receptor 1 (Drd1) showed rhythmic expression with peak expression during the dark phase regardless of light-testing condition. Next, we performed drug challenges in a new rat cohort to examine the interaction between the cholinergic and dopaminergic neurotransmitter systems in regulating the behavioral changes caused by circadian disruption. We administered the cholinergic agonist nicotine and either the dopamine-1 receptor (DR1) antagonist SCH23390 or the DR2 antagonist eticlopride under the 3 circadian conditions to identify differential drug responses between treatment groups. Rats in both models demonstrated increased sensitivity to nicotine as compared to control, while SCH23390 and eticlopride ameliorated the effect of nicotine on 5-CSRTT performance in both models. Our study is the first to identify detrimental effects of both models of circadian disruption on impulsive behavior, and that the effects of circadian disruption are mediated by an interaction between cholinergic and dopaminergic systems.

Assessing gastroenterologist and patient acceptance of biosimilars in ulcerative colitis and Crohn's disease across Germany.

OBJECTIVES: This study examined gastroenterologists' motivation for prescribing biosimilars, assessed their treatment preferences in relation to prescribing behaviour, and explored patient attitudes to biosimilars. METHODS: Data were taken from the Adelphi Real World Biosimilars Programme, a real-world, cross-sectional study undertaken in 2015-2016 with German gastroenterologists and patients with ulcerative colitis or Crohn's disease. Gastroenterologists provided data on their prescribing behaviour and attitudes towards biosimilars, and invited the next eight eligible consecutive consulting patients to complete a detailed questionnaire. For analysis, gastroenterologists were split into 'Investigative', 'Conservative', and 'Other' groups. RESULTS: Overall, 25 gastroenterologists and 136 patients participated. Biosimilars accounted for <15% of all biologic therapies and >80% of gastroenterologists would prescribe a bio-originator rather than biosimilar as 1st line therapy if unrestricted. Patients showed some reluctance to accept biosimilars, although of those receiving biosimilars, 79% were satisfied with the current treatment of their condition, and 69% were satisfied with the control of symptoms. Although at least 35% of patients in each analysis group reported no concerns when starting treatment with a bio-originator or biosimilar, 41% of previously biologic-naïve patients prescribed a biosimilar indicated potential side effects and potential long-term problems, and 24% not knowing enough about the drug, as concerns. CONCLUSION: Results demonstrate that there is reluctance from patients to accept biosimilars and the need to further educate patients who are unsure to allow them to be involved in decision making, highlighting the importance of patient and physician communication. There remains a need for further research into non-clinical switching and the long term impact of prescribing biosimilars.

Misalignment between physicians and patient satisfaction with psoriatic arthritis disease control.

The main objective of the present study is to evaluate the misalignment between psoriatic arthritis (PsA) patient- and physician-reported satisfaction with PsA control. Data came from the Adelphi Rheumatology Disease Specific Programme, a retrospective, cross-sectional survey of US-based rheumatologists and patients. Physicians provided satisfaction and clinical characteristics on tender joint count, swollen joint count, and percent body surface area (BSA) affected by psoriasis. Patients provided data on satisfaction, the Work Productivity Activity Impairment and Health Assessment Questionnaire-Disability Index (HAQ-DI) questionnaires. Based on their satisfaction response, patient-physician pairs were classified into aligned (both satisfied or dissatisfied) or misaligned (rated satisfaction differently) groups. Multivariate analysis evaluated association of characteristics with misalignment. Among 305 paired patient-physician records analyzed, 23.6% were misaligned and 76.4% were aligned. The misaligned group had shorter disease duration (mean years, 5.2 vs. 6.4), used fewer biologic disease-modifying antirheumatic drugs (49.3 vs. 62.9%), had more swollen (mean, 3.7 vs. 1.9, P = 0.0002) and tender joints (mean, 5.6 vs. 2.9, P < 0.0001), greater proportion of patients with comorbidities (72.2 vs. 63.1%), and >3% BSA affected by psoriatic skin lesions (64.2 vs. 55.1%). Misaligned patients reported greater work impairment (mean, 38.7 vs. 21.4, P = 0.0004), daily activities (mean, 38.7 vs. 22.3, P < 0.0001), and higher disease burden (mean HAQ-DI; 0.56 vs. 0.37, P = 0.0001). Multivariate analysis found the number of swollen joints (P = 0.02) and HAQ-DI score (P = 0.03) was significantly associated with misalignment among all patients; however, not in the subgroup of employed patients. Patient-physician misalignment is associated with increased disease activity and disability among patients with PsA.

The effects of a UK review of Breast Cancer Screening on Uptake: an observational before/after study.

OBJECTIVES: To measure whether uptake of breast cancer screening was affected by the publication of the Marmot Review and associated press coverage. SETTING: Eight NHS breast screening centres in the West Midlands of the UK. METHODS: Uptake of breast cancer screening invitations was compared in the week before and after the Marmot review publication. All 12,023 women invited for screening between 23 October 2012 and 5 November 2012 were included. A mixed effects model of the predictors of screening uptake (on date invited, or within 21 days) was created. Predictors considered for inclusion were whether the allocated screening appointment was before or after publication of the review, population factors (age, index of multiple deprivation income domain by quintile, previous attendance), and interaction terms. RESULTS: Uptake decreased after publication of the review from 65% to 62% (OR = 0.87 95%CI = 0.80-0.94), but a similar decrease was seen for the same dates on the previous year (OR = 0.85 95%CI = 0.78-0.93). Odds of attending screening were lower for women in the most deprived (uptake = 49%, OR = 0.54, 95%CI = 0.46-0.62) in comparison with the least deprived quintile (uptake = 71%). Odds of attendance also increased if the woman had ever previously attended (OR 3.9 95% CI 3.5-4.4), and decreased with each year of increasing age (OR 0.96 95% CI 0.96-0.97). There were no interactions between any of the other predictors and whether the appointment was before or after publication of the Marmot review. CONCLUSION: No change in uptake of breast cancer screening above normal seasonal variation was detected after publication of the Marmot review.

Invitation management initiative to improve uptake of breast cancer screening in an urban UK Primary Care Trust.

OBJECTIVES: In an attempt to improve breast cancer screening uptake and coverage, persistent non-attenders in the Heart of Birmingham Teaching Primary Care Trust were included in an invitation management initiative. METHODS: Persistent non-attenders were identified in routine screening lists. Phone contact was attempted or a home visit was made. If the case was not resolved, a second appointment was made and further phone calls and home visits were attempted. RESULTS: Of 548 persistent non-attenders identified, 228 (42%) declined screening, 171 (31%) attended, 72 (13%) had moved away or died, 11 (2%) were recently screened or under care for other conditions. Sixty-six cases (12%) remained unresolved. Fourteen women opted to be permanently withdrawn from the National Health Service Breast Screening Programme (NHSBSP). Twenty-four women had a negative experience of breast cancer screening (defaulted, recalled for assessment, recalled for technical reasons). No malignancies were found. A total of 1375 phone calls and 230 home visits were attempted. Uptake would have been 62.2% if none of the persistent non-attenders included in the initiative had attended for screening. With the initiative, uptake of breast cancer screening was increased to 65.3%. CONCLUSIONS: Phone calls and home visits resulted in only a moderate increase in breast cancer screening uptake. The initiative encouraged nervous attenders who were reassured about the screening process. However, more women declined screening than were screened and the initiative made it easier for women to request to be permanently withdrawn from the NHSBSP.

Screening histories of invasive breast cancers diagnosed 1989-2006 in the West Midlands, UK: variation with time and impact on 10-year survival.

OBJECTIVES: To examine variations in screening status category with time for 20,862 invasive breast cancers diagnosed in the West Midlands between 1989 and 2006, and to provide 10-year relative survival rates for each category. METHOD: Population-based breast screening was introduced in the West Midlands from 1988. Primary invasive breast cancers diagnosed from 1 April 1989 to 31 March 2006 in women eligible for breast screening were identified from the West Midlands Cancer Intelligence Unit's cancer registration database. A screening status was determined for each case using previously published methodology. RESULTS: Screening status rates are affected initially by the gradual rollout of the screening programme and more recently by the need to wait for three years before interval cancers and cancers in lapsed and non-attenders can be identified. In the steady-state period 1994-2003, 40.6% of invasive breast cancers were screen-detected, 36.3% were interval cancers and 11.2% were cancers in non-attenders (NA). Ten-year relative survival was 89.6% for screen-detected breast cancers, 73.3% for interval cancers and 51.9% for cancers in NA. CONCLUSION: The detection of invasive breast cancers by screening has improved over time, with an equivalent reduction in the numbers of interval cancers. This, together with a stable rate of cancers in NA and an improvement in the survival of women with interval cancers, suggests that further improvements in breast cancer mortality can be predicted. International comparisons of interval cancer rates are difficult due to interprogramme differences in the time between screens.

Population estimates of survival in women with screen-detected and symptomatic breast cancer taking account of lead time and length bias.

BACKGROUND: Evidence of the impact of breast screening is limited by biases inherent in non-randomised studies and often by lack of complete population data. We address this by estimating the effect of screen detection on cause-specific fatality in breast cancer, corrected for all potential biases, using population cancer registry data. METHODS: Subjects (N = 26,766) comprised all breast cancers notified to the West Midlands Cancer Intelligence Unit and diagnosed in women aged 50-74, from 1988 to 2004. These included 10,100 screen-detected and 15,862 symptomatic breast cancers (6,009 women with interval cancers and 9,853 who had not attended screening). Our endpoint was survival to death from breast cancer. We estimated the relative risk (RR) of 10-year cause-specific fatality (screen-detected compared to symptomatic cancers) correcting for lead time bias and performing sensitivity analyses for length bias. To exclude self-selection bias, survival analyses were also performed with interval cancers as the comparator symptomatic women. FINDINGS: Uncorrected RR associated with screen-detection was 0.34 (95% CI 0.31-0.37). Correcting for lead time, RR was 0.49 (95% CI 0.45-0.53); length bias analyses gave a range of RR corrected for both phenomena of 0.49-0.59, with a median of 0.51. Self-selection bias-corrected estimates yielded a median RR of 0.68. INTERPRETATION: After adjusting for various potential biases, women with screen-detected breast cancer have a substantial survival advantage over those with symptomatic breast cancer.

Correcting for lead time and length bias in estimating the effect of screen detection on cancer survival.

Determination of survival time among persons with screen-detected cancer is subject to lead time and length biases. The authors propose a simple correction for lead time, assuming an exponential distribution of the preclinical screen-detectable period. Assuming two latent categories of tumors, one of which is more prone to screen detection and correspondingly less prone to death from the cancer in question, the authors have developed a strategy of sensitivity analysis for various magnitudes of length bias. Here they demonstrate these methods using a series of 25,962 breast cancer cases (1988-2004) from the West Midlands, United Kingdom.

The West Midlands breast cancer screening status algorithm - methodology and use as an audit tool.

OBJECTIVES: To illustrate the ability of the West Midlands breast screening status algorithm to assign a screening status to women with malignant breast cancer, and its uses as a quality assurance and audit tool. METHODS: Breast cancers diagnosed between the introduction of the National Health Service [NHS] Breast Screening Programme and 31 March 2001 were obtained from the West Midlands Cancer Intelligence Unit (WMCIU). Screen-detected tumours were identified via breast screening units, and the remaining cancers were assigned to one of eight screening status categories. Multiple primaries and recurrences were excluded. RESULTS: A screening status was assigned to 14,680 women (96% of the cohort examined), 110 cancers were not registered at the WMCIU and the cohort included 120 screen-detected recurrences. CONCLUSIONS: The West Midlands breast screening status algorithm is a robust simple tool which can be used to derive data to evaluate the efficacy and impact of the NHS Breast Screening Programme.