Rate Of False-negative Findings Research Articles

Abstract PS3-27: 18F-FDG-PET/CT and MRI in the assessment of neoadjuvant chemotherapy treatment response in breast cancer. Correlation with pathological response

Abstract Introduction: Residual cancer burden (RCB) after neoadjuvant chemotherapy (NAC) can accurately predict disease recurrence and survival in breast cancer. In this context, end of treatment (EOT) image-guided response assessment could be useful to adapt treatment for individual patients. Our main objective was to assess the effectiveness of 18F-FDG PET/CT and MRI in determining NAC response. Methods: Patients with surgically resectable breast cancer (stages II-III) were prospectively included and evaluated with 18F-FDG-PET/CT and MRI before and after standard-of-care neoadjuvant chemotherapy (NAC). Ultrasound guided breast biopsy was performed before NAC and pathologic examination with residual cancer burden (RCB) scoring was performed after surgery. Standard uptake values (SUVmax and SUVmean) from baseline PET scans were measured. EOT images results were compared with RCB scores to assess the sensitivity and specificity of (EOT) 18F-FDG-PET/CT and MRI images. A multinomial logistic regression was performed to assess predictors of pathological response. A p-value of 0.05 was considered significant. Results: 30 patients were included, with 25% showing complete pathological response. EOT 18F-FDG-PET/CT images had a sensitivity of 55% and specificity of 100% to predict RCB > 0, while EOT MRI had a sensitivity of 65% and specificity of 66,6%. Luminal tumors showed significant lower baseline SUVmean and SUVmax values than triple-negative tumors. Ki67 expression didn´t correlate with treatment outcome. High estrogen receptor expression level was significantly associated with non-complete pathological response and higher false negative rates in both EOT 18F-FDG-PET and MRI images (7/8 in PET and 6/7 in MRI). Conclusions: 18F-FDG-PET / CT could be a useful diagnostic tool to assess neoadjuvant chemotherapy treatment response in breast cancer, showing greater specificity than MRI to predict pathological response. A high expression of estrogen receptors could lead to a high rate of false negative findings, both in PET and MRI. A greater number of cases is required to validate these findings. Citation Format: Marco Guarin, M. Eugenia Azar, Carolina Tinetti, M. Dolores Mansilla F., Mauro Namias, Pilar Carballo, Lucia Santamarina, Jorgelina Cavallero, Romina Moreau, Christian Gonzalez, Valeria Caceres, Eduardo Gonzalez, Gabriel Bruno. 18F-FDG-PET/CT and MRI in the assessment of neoadjuvant chemotherapy treatment response in breast cancer. Correlation with pathological response [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-27.

Coronary CT angiography (CCTA) using third-generation dual-source CT for ruling out in-stent restenosis

Late in-stent restenosis (ISR) has become increasingly important, in particular due to neo-atherosclerosis. CCTA is a highly sensitive method for detecting coronary plaques. Its diagnostic accuracy regarding ISR is controversial. Stent artifacts can impede image quality, but recent developments in CT-technology may help to overcome some of these problems and allow for improved diagnostic accuracy. Consecutive patients after previous coronary revascularization who had stable symptoms or signs of possible disease progression were examined using a third-generation dual-source CT scanner. After the scan, patients were followed for clinical events (MACE) over a mean of 399 days. Patients with high-grade stenoses were referred for invasive coronary angiography (ICA), unclear findings were further evaluated either by ICA or functional testing. Overall, 226 patients were included. A total of 457 stents were evaluated (2.0 ± 1.4 per patient). Mean stent diameter was 2.9 ± 0.45mm. In 61%, a high-pitch protocol was employed. Mean dose-length product (DLP) of CCTA was 159.2 mGycm, corresponding to 2.2mSv using a conversion factor of k = 0.014. Mean amount of contrast agent was 58.3 ± 12.5ml. In 145 patients (64%), CCTA was negative. In this group, one MACE occurred (acute coronary syndrome) during follow-up in a patient who had also undergone unremarkable ICA. In 23 patients (10%), CCTA detected 28 ISR which were confirmed and treated by ICA (true positive). In 27 patients (12%), ISR was suspected by CCTA but excluded by ICA (false positive), 30 patients (13%) had unclear findings and normal non-invasive tests. No MACE occurred during follow-up in these patients. One patient was misclassified in CCTA as having intermediate and not high-grade ISR who underwent revascularization within 3 months. Eleven patients (5%) were lost to follow-up. During follow-up, eight patients had myocardial infarctions due to five ISRs and three de novo lesions. No patient died. In cases with unclear or false-positive findings, the amount of stents was significantly higher, stents were smaller and patients had a higher BMI. In almost two-thirds of symptomatic patients with previous coronary stent implantation, ISR could be ruled out by CCTA. 10% of patients had definite ISR. The rate of false-negative findings was low (< 1%), whereas the rate of false positive or inconclusive findings was 25%, leading to invasive rule-out of ISR by ICA in 12%. CCTA appears valuable as a tool for safely excluding ISR. It might help to avoid invasive diagnostic procedures. Further analyses are warranted, in particular regarding the influence of stent dimensions and the total amount of stents in a patient.

Rate of false-negative findings in sentinel lymph node biopsy in patients with head and neck malignant melanoma.

e17566 Background: Sentinel Lymph Node Biopsy (SLNB) is the standard procedure for malignant melanoma with a thicknes above 1mm. However, the benefits of this procedure have recently been questioned because of a high number of false negative findings. The aim of our study was to investigate the number of early recurrence in patients with negative SLNB. Methods: All patients with malignant melanoma of the head and neck region who underwent SLNB between 2010 and 2016 in our department were included and data reviewed retrospectively. Recurrence in the same cervical lymph node region of the previously extirpated sentinel lymph node (SLN) within one year was defined as primary false-negative. Results: Allover 101 patients were investigated (mean age 62.48 years (±17.66; 73.3% ♂, 26.7% ♀). Most frequent location of the primary melanoma were the cheeks and ears (each 18.8%), followed by the hair bearing region (13.9%). Superficial Spreading Melanoma and Nodular Melanoma were the most frequently seen subtypes (each 23.8%), followed by Lentigo maligna Melanoma (19.8%). Median thickness of all patients was 2.5mm (min: 0.15 – max: 10.0 mm). In average 3 SLN were removed during operation (min: 1 – max 16). In 79.2% of the cases the SLN was negative. 13% showed one metastasis, 5.2% showed two and 1.6% three metastases. Positive findings in the SLN were significantly correlated with T-classification. Ulceration and tumor thickness showed significant tendencies in Χ2-Test and Mann-Whitney-Test. Out of the patients with negative SLN 13.1% had at least one metastasis in a cervical lymph node of the same region within one year. Mean duration until recurrence was 6.5 months. 75.0% of the metastases in our study were diagnosed within this period. 62.5% of the patients with secondary positive SLN had a tumor of intermediate thickness (between 1mm and 4mm). Conclusions: With 13.1 % secondary positive SLN this study shows that SLNB has a high rate of false-negative findings. However, SLNB has lower complication rates compared to traditional lymph node extirpation. This study shows that patients with negative SLN especially with intermediate tumor thickness should be controlled by ultrasound or computer tomography in short intervals.

Indications for Pelvic Nodal Treatment in Prostate Cancer Should Change. Validation of the Roach Formula in a Large Extended Nodal Dissection Series

Previous studies have criticized the predicting ability of the Roach formula in assessing the risk of lymph node invasion (LNI) in contemporary patients with prostate cancer (PCa) due to a significant overestimation of LNI rates. However, all those studies included patients treated with limited pelvic lymph node dissection (PLND), which is associated with high rates of false negative findings. We hypothesized that the Roach formula is still an accurate tool for LNI predictions if an extended PLND (ePLND) is performed. We included 3,115 consecutive patients treated with radical prostatectomy and ePLND between 2000 and 2010 at a single tertiary referral center. Extended PLND consisted of removal of obturator, external iliac, and hypogastric lymph nodes. We externally validated the Roach formula by using the area under the receiver operating characteristics curve and calibration plot method. Moreover, we tested the performance characteristics of different formula-generated cutoff values ranging from 1% to 20%. The accuracy of the Roach formula was 80.3%. The calibration showed only a minor underestimation of the LNI risk in high-risk patients (6.7%). According to the Roach formula, the use of 15% cut off would have allowed 74.2% (2,311/3,115) of patients to avoid nodal irradiation, while up to 32.7% (111/336) of all patients with LNI would have been missed. When the cut off was lowered to 6%, nodal treatment would have been spared in 1,541 (49.5%) patients while missing 41 LNI patients. The sensitivity, specificity, and negative predictive values associated with the 6% cut off were 87.9%, 54%, and 97.3%, respectively. The Roach formula is still accurate and does not overestimate the rate of LNI in contemporary prostate cancer patients if they are treated with ePLND. However, the recommended cut off of 15% would miss approximately one-third of patients with LNI. Based on our results, the cut off should be lowered to 6%.

Sentinel Lymph Nodes in Early Stage Cervical Cancer

Lymph node status is thought to be the strongest prognostic factor in women with cervical cancer. Sentinel lymph node (SLN) procedures reportedly shorten operating time and lower the risk of perioperative and postoperative morbidity. Patients with breast cancer have experienced an improved quality of life following SLN biopsy. At the authors' center, all patients operated on for clinical FIGO stage IA/B1 cervical cancer now undergo SLN detection before pelvic lymphadenectomy and radical hysterectomy or radical trachelectomy. The value of the SLN procedure was assessed in 39 patients who subsequently underwent full pelvic lymphadenectomy. The SLN was detected by injecting technetium-labeled sulfur colloid submucosally into all 4 quadrants of the exocervix. Lymphazurin was used only if technetium failed to identify SLNs on both sides. Microsections were made at 5-μm intervals and stained intraoperatively in preparation for comprehensive pelvic lymph node dissection. Nearly 60% of patients in this study had stage IB 1 disease. Squamous-cell carcinomas and adenocarcinomas were equally frequent. Laparoscopic radical hysterectomy was carried out in 56% of patients, radical vaginal trachelectomy in 38%, and abdominal radical hysterectomy in 5%. At least 1 SLN was detected in 98% of patients and 85% of sides. Bilateral SLNs were identified in 72% of cases. The median number of SLNs per side was 2. Three patients had metastatic tumor in lymph nodes; 2 of them were correctly diagnosed by the SLN procedure. There were no false-negative results, and identifying SLNs caused no adverse side effects. In this study, the SLN procedure was 100% sensitive and specific, and had positive and negative predictive values of 100%. The investigators believe that SLN biopsy is feasible in women having surgery for cervical cancer, and the rate of false-negative findings is low. Sentinel nodes should be evaluated not on a per-patient, but rather on a per-side basis.

Localizing the rostrolateral prefrontal cortex at the individual level

The functions of the rostrolateral prefrontal cortex (RLPFC) have recently become the target of multiple theories and empirical investigations. This region can be loosely defined as the lateral portion of Brodmann area (BA) 10. One of the challenges in testing theories about RLPFC functions is the difficulty in defining its boundaries when formulating predictions for its recruitment. Here we present a procedure that goes beyond the currently available anatomical definitions to attempt a functional localization of RLPFC. A combination of functional and anatomical criteria was employed, consistent with other localizer procedures. Functional localization was performed by comparing a relational condition involving relational matching to a control condition involving feature matching. It was expected that within an anatomically defined BA10 region, this procedure would produce functional activations in the lateral but not the medial subregions. The task was administered in the course of a single 13-min fMRI session. Results showed remarkable consistency, with all subjects activating RLPFC and activations consistently localized in the lateral part of BA10. These results demonstrate the practical feasibility of localizing RLPFC using a short procedure and a combination of functional and anatomical criteria. Such localization presents with a number of potential advantages for testing theories of RLPFC functions, including improved anatomical precision of experimental predictions, as well as the possibility of reduction in the rate of false-negative findings across studies. In addition, the results provide further support for the previously proposed functional dissociation between lateral and medial BA10.

San Antonio Breast Cancer Symposium - Highlights 2004

The adjuvant therapy of postmenopausal, hormonereceptor positive breast cancer patients with aromatase inhibitors in ATAC, ABCSG 8/ ARNO 95 and IES trial revealed just a benefit in terms of disease-free survival, but not for over-all survival. Thus MA-17 trial is so far the only study which could demonstrate a survival benefit for node positive disease by "extended adjuvant" therapy with letrozole. Node- and receptorpositive, postmenopausal women show a higher benefit by anthracycline containing chemotherapy in combination with tamoxifen, than by endocrine therapy alone. But tamoxifen should given sequentially to chemotherapy (Intergroup 0100/ SWOG-8814 trial). Adjuvant chemotherapy with three cycles FEC followed by three cycles docetaxel reveals a survival benefit compared to six cycles FEC, especially in women older than 50 years (PACS 01 trial). Furthermore there is evolving evidence that dose-dense, interval shortened chemotherapy is superior to standard chemotherapy in adjuvant setting. The impaired survival of receptornegative, nodalpositive breast cancer patients seems to be converted to a survival improvement compared with receptorpositive patients by modern adjuvant cytotoxic regimens (metaanalysis CALGB 8541, 9344, 9741). In primary systemic chemotherapy survival is strongly associated with the rate of pathohistological complete remissions (NSABP B-27). The combination of cytotoxic drugs has no further influence on survival, but the sequential administration of taxane increases the rate of pCR. A difference in survival stratified by pCR and non-pCR in breast and positive nodal status could not be detected, so that the number of involved lymph nodes seems to be the strongest prognostic factor and is independent of tumor response in the breast. The sentinel node biopsy is a safe and reliable method, but the rate of false negative findings depends on the pathohistological methods (NSABP B-32). The morbidity of this method is low compared with conventional axillary dissection in multicenter studies. Local tumor control is an important parameter which offers a significant survival benefit in all age cohorts.

How to detect effects: statistical power and evidence-based practice in occupational therapy research.

The findings from 30 research investigations examining the effectiveness of occupational therapy interventions were reviewed and analyzed. The statistical conclusion validity was determined by computing post hoc power coefficients for the statistical hypothesis tests included in the examined studies. Data analysis revealed the median power values to detect small, medium, and large effect sizes were .09, .33, and .66, respectively. These results suggest a high probability of Type II errors in the sample of occupational therapy intervention research examined. In practical terms, this means the intervention produced a potentially useful treatment effect, but the effect was not detected as significant. Examples are provided that illustrate how low statistical power contributes to increases in Type II errors and inhibits the development of consensus through replication in the research literature. The presence of low-power studies with high rates of false negative findings prevents the establishment of guidelines for evidence-based practice and impedes the scientific progress of rehabilitation professions such as occupational therapy.

Accuracy of Melanoma Screening

Dermatologists in the United States perform visual skin cancer screenings on a regular basis. Reports of large numbers of new skin cancers detected during screening are impressive, but the accuracy of skin cancer screening has not been studied extensively. To determine the rate of false negative findings in a Dutch skin cancer screening program …

Intraoperative Ultrasound Imaging of the Liver at the Time of Colorectal Cancer Resection

To evaluate the accuracy of intraoperative ultrasound (IOUS) liver imaging at the time of primary colorectal cancer resection, which might eliminate incurable patients from adjuvant chemotherapy trials or permit earlier resection of curable metastases. A prospective trial of routine IOUS liver imaging during resections of primary colorectal cancer. The rate of detection of occult metastases by IOUS imaging alone and the false-negative rate over 22.7 months of follow-up were determined. A tertiary care referral center in Boston, Mass. Fifty-five patients undergoing 56 operations for colorectal carcinoma between May 1990 and June 1992. The rate of detection, by IOUS imaging alone, of otherwise occult hepatic metastases, the total number of patients with metastases detected at any time during follow-up, and the rate of false-negative findings on IOUS imaging and direct examination. Occult hepatic metastases were detected by IOUS imaging alone in 5% of patients. Restriction of IOUS imaging to patients with T3 or T4 lesions or recurrent cancers would have identified all metastases and increased the detection rate to 10%. Occult metastases were detected by IOUS imaging alone in 12.5% of patients with T3, N0 lesions. The rate of false-negative findings on IOUS imaging was 13% overall, 0% for patients with T1 or T2 lesions, 3% for patients with node-negative findings, and 7% for patients with T3, N0 lesions. The small increment in the detection of occult metastases by IOUS liver imaging does not warrant its use in all patients with colorectal cancer. Selective use in patients with T3 or T4 lesions or recurrent cancers increased the incremental gain in detection. The observed frequency of occult metastases in patients with T3, N0 lesions is sufficient to impact on results of adjuvant chemotherapy trials. Longer follow-up in more patients is needed to determine whether a negative IOUS study is an additional favorable prognosticator in patients with T1 and T2 lesions and node-negative findings.