Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk breast cancer patients: the ABLATIVE-2 trial-a study protocol.

BACKGROUND: Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients. METHODS: The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy. DISCUSSION: This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6-8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients. TRIAL REGISTRATION: The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).

Ultra-low-dose CT versus chest X-ray for patients suspected of pulmonary disease at the emergency department: a multicentre randomised clinical trial.

BACKGROUND: Chest CT displays chest pathology better than chest X-ray (CXR). We evaluated the effects on health outcomes of replacing CXR by ultra-low-dose chest-CT (ULDCT) in the diagnostic work-up of patients suspected of non-traumatic pulmonary disease at the emergency department. METHODS: Pragmatic, multicentre, non-inferiority randomised clinical trial in patients suspected of non-traumatic pulmonary disease at the emergency department. Between 31 January 2017 and 31 May 2018, every month, participating centres were randomly allocated to using ULDCT or CXR. Primary outcome was functional health at 28 days, measured by the Short Form (SF)-12 physical component summary scale score (PCS score), non-inferiority margin was set at 1 point. Secondary outcomes included hospital admission, hospital length of stay (LOS) and patients in follow-up because of incidental findings. RESULTS: 2418 consecutive patients (ULDCT: 1208 and CXR: 1210) were included. Mean SF-12 PCS score at 28 days was 37.0 for ULDCT and 35.9 for CXR (difference 1.1; 95% lower CI: 0.003). After ULDCT, 638/1208 (52.7%) patients were admitted (median LOS of 4.8 days; IQR 2.1-8.8) compared with 659/1210 (54.5%) patients after CXR (median LOS 4.6 days; IQR 2.1-8.8). More ULDCT patients were in follow-up because of incidental findings: 26 (2.2%) versus 4 (0.3%). CONCLUSIONS: Short-term functional health was comparable between ULDCT and CXR, as were hospital admissions and LOS, but more incidental findings were found in the ULDCT group. Our trial does not support routine use of ULDCT in the work-up of patients suspected of non-traumatic pulmonary disease at the emergency department. TRIAL REGISTRATION NUMBER: NTR6163.

Bone suppression increases the visibility of invasive pulmonary aspergillosis in chest radiographs.

OBJECTIVE: Chest radiographs (CXR) are an important diagnostic tool for the detection of invasive pulmonary aspergillosis (IPA) in critically ill patients, but their diagnostic value is limited by a poor sensitivity. By using advanced image processing, the aim of this study was to increase the value of chest radiographs in the diagnostic work up of neutropenic patients who are suspected of IPA. METHODS: The frontal CXRs of 105 suspected cases of IPA were collected from four institutions. Radiographs could contain single or multiple sites of infection. CT was used as reference standard. Five radiologists and two residents participated in an observer study for the detection of IPA on CXRs with and without bone suppressed images (ClearRead BSI 3.2; Riverain Technologies). The evaluation was performed separately for the right and left lung, resulting in 78 diseased cases (or lungs) and 132 normal cases (or lungs). For each image, observers scored the likelihood of focal infectious lesions being present on a continuous scale (0-100). The area under the receiver operating characteristics curve (AUC) served as the performance measure. Sensitivity and specificity were calculated by considering only the lungs with a suspiciousness score of greater than 50 to be positive. RESULTS: The average AUC for only CXRs was 0.815. Performance significantly increased, to 0.853, when evaluation was aided with BSI (p = 0.01). Sensitivity increased from 49% to 66% with BSI, while specificity decreased from 95% to 90%. CONCLUSION: The detection of IPA in CXRs can be improved when their evaluation is aided by bone suppressed images. BSI improved the sensitivity of the CXR examination, outweighing a small loss in specificity.

Observer training for computer-aided detection of pulmonary nodules in chest radiography.

OBJECTIVES: To assess whether short-term feedback helps readers to increase their performance using computer-aided detection (CAD) for nodule detection in chest radiography. METHODS: The 140 CXRs (56 with a solitary CT-proven nodules and 84 negative controls) were divided into four subsets of 35; each were read in a different order by six readers. Lesion presence, location and diagnostic confidence were scored without and with CAD (IQQA-Chest, EDDA Technology) as second reader. Readers received individual feedback after each subset. Sensitivity, specificity and area under the receiver-operating characteristics curve (AUC) were calculated for readings with and without CAD with respect to change over time and impact of CAD. RESULTS: CAD stand-alone sensitivity was 59 % with 1.9 false-positives per image. Mean AUC slightly increased over time with and without CAD (0.78 vs. 0.84 with and 0.76 vs. 0.82 without CAD) but differences did not reach significance. The sensitivity increased (65 % vs. 70 % and 66 % vs. 70 %) and specificity decreased over time (79 % vs. 74 % and 80 % vs. 77 %) but no significant impact of CAD was found. CONCLUSION: Short-term feedback does not increase the ability of readers to differentiate true- from false-positive candidate lesions and to use CAD more effectively. KEY POINTS: • Computer-aided detection (CAD) is increasingly used as an adjunct for many radiological techniques. • Short-term feedback does not improve reader performance with CAD in chest radiography. • Differentiation between true- and false-positive CAD for low conspicious possible lesions proves difficult. • CAD can potentially increase reader performance for nodule detection in chest radiography.

Computer-aided detection of lung cancer on chest radiographs: effect on observer performance.

PURPOSE: To assess how computer-aided detection (CAD) affects reader performance in detecting early lung cancer on chest radiographs. MATERIALS AND METHODS: In this ethics committee-approved study, 46 individuals with 49 computed tomographically (CT)-detected and histologically proved lung cancers and 65 patients without nodules at CT were retrospectively included. All subjects participated in a lung cancer screening trial. Chest radiographs were obtained within 2 months after screening CT. Four radiology residents and two experienced radiologists were asked to identify and localize potential cancers on the chest radiographs, first without and subsequently with the use of CAD software. A figure of merit was calculated by using free-response receiver operating characteristic analysis. RESULTS: Tumor diameter ranged from 5.1 to 50.7 mm (median, 11.8 mm). Fifty-one percent (22 of 49) of lesions were subtle and detected by two or fewer readers. Stand-alone CAD sensitivity was 61%, with an average of 2.4 false-positive annotations per chest radiograph. Average sensitivity was 63% for radiologists at 0.23 false-positive annotations per chest radiograph and 49% for residents at 0.45 false-positive annotations per chest radiograph. Figure of merit did not change significantly for any of the observers after using CAD. CAD marked between five and 16 cancers that were initially missed by the readers. These correctly CAD-depicted lesions were rejected by radiologists in 92% of cases and by residents in 77% of cases. CONCLUSION: The sensitivity of CAD in identifying lung cancers depicted with CT screening was similar to that of experienced radiologists. However, CAD did not improve cancer detection because, especially for subtle lesions, observers were unable to sufficiently differentiate true-positive from false-positive annotations.