Discordance Rate Research Articles

Biomarker Discordances and Alterations Observed in Breast Cancer Treated with Neoadjuvant Chemotherapy: Causes, Frequencies, and Clinical Significances

Biomarker discordances and alterations can be encountered between tru-cut biopsy and residual tumor in breast cancer treated with neoadjuvant chemotherapy (NACTx). We aimed to investigate the effect of NACTx on major biomarker expression (ER, PR, HER2, Ki-67) and tumor grade, the frequency and causes of receptor discordances, and the clinical significance of changes in terms of adjuvant therapy need and chemosensitivity. In this retrospective study, ER, PR, HER2, and Ki-67 expression and tumor grades were compared between pre- and post-NACTx tumor samples using the Wilcoxon signed-rank test. The frequencies of receptor discordances and the need for new adjuvant therapy due to discordances were calculated. The effect of patient and tumor characteristics and NACTx regimens on discordances was investigated using multivariate analysis. Using histopathological examinations, residual tumors were divided into chemotherapy-responsive and chemotherapy-unresponsive tumors. Biomarker changes in both groups were analyzed for predictability of chemosensitivity. Of the 169 patients who received NACTx, 102 patients having enough residual tumors in the surgical pathology specimen were enrolled in the study. Histopathologically, about 70% of tumors were partially responsive to NACTx and 30% were unresponsive (chemo-resistant). The concordance and discordance rates were 95.1% versus 4.9% for ER (p = 0.180), 97.1% versus 2.9% for PR (p = 0.083), and 89.2% versus 10.8% for HER2 (p = 0.763), respectively. In addition, 15% of hormone receptor (HR)-negative patients became HR(+) and 5.7% of HER2(-) patients became HER2(+) in the residual tumors, requiring adjuvant endocrine or anti-HER2 therapy. In particular, 18% of triple-negative patients became HR(+) and 12% became HER2(+). HER2 loss was detected in 40% of HER2(+) patients. Multivariate logistic regression analysis revealed that lower estrogen expression (p = 0.046), a smaller tumor size (p = 0.029), and anti-HER2 therapy (p < 0.001) have independent efficacy on ER discordance, PR discordance, and HER2 discordance, respectively. Ki-67 and PR expression significantly decreased in chemotherapy-responsive tumors (p = 0.001 and p = 0.004), and the tumor grade increased in chemotherapy-unresponsive tumors (p = 0.034). Approximately 3-5% of HR discordance and about 10% of HER2 discordance can be observed in breast cancer after currently used NACTx regimens. Discordances are bi-directional (from positive to negative and vice versa), and their causes are multifactorial; they should be assessed accordingly. The NACTx effect alone cannot explain observed discordances but can cause biomarker alterations. The change in receptor status from positive to negative, especially HER2 loss, is mainly associated with the NACTx effect. However, the shift from negative to positive is thought to be primarily related to intratumoral heterogeneity. Receptor statuses becoming positive are of more clinical importance due to adjuvant therapy requirements. Biomarker alterations in PR, Ki-67, and tumor grade can provide predictive information about tumor chemosensitivity.

The utility of the bilateral temporal artery biopsy for diagnosis of giant cell arteritis.

A surgical temporal artery biopsy (TAB) is the gold standard for diagnosis of giant cell arteritis (GCA). The necessity of performing a bilateral biopsy remains under debate. The primary objective of this study was to assess the rate of discordance between pathology results in patients who underwent bilateral TAB for suspected GCA. We performed a retrospective review of patients who underwent bilateral TAB for the diagnosis of GCA between 2011 and 2020. The primary end point was the rate of discordance between specimens for patients with pathology positive GCA. Secondary end points included assessments of the sensitivity of preoperative temporal artery duplex and the effects of specimen length and specialty of referring provider on the diagnostic yield of the biopsy. During the study period, 310 patients underwent bilateral TAB for the diagnosis of GCA. These patients were primarily female (73.9%), elderly (mean age, 70.8years), and Caucasian (95.8%). Preoperative symptoms for patients were typically bilateral (59%) and included headache (81%), vision changes (45.2%), and temporal tenderness (32.6%). Most patients (85.2%) were on preoperative steroid therapy at the time of surgical biopsy with a mean preoperative duration of steroid therapy of 15.1days. Overall, 91 patients (29.4%) had a positive pathologic diagnosis after bilateral TAB. Of these patients, 11 had a positive pathology result in only a single specimen, resulting in a discordance rate of 12.1%. Preoperative temporal artery duplex demonstrated a low sensitivity (27.3%) for identifying patients with pathologic positive disease. There were no significant differences between the pathology-positive and -negative patients in terms of mean surgical specimen length (1.67cm vs 1.64cm; P= .67) or the specialty of the referring provider (P= .73). At our institution, we observed a 12.1% discordance rate between pathology results in patients who underwent bilateral TAB for diagnosis of GCA. A preoperative temporal artery duplex provided little value in identifying patients with biopsy-proven GCA.

Changes in interpretation of spirometry by implementing the GLI 2012 reference equations: impact on patients tested in a hospital-based PFT lab in a large metropolitan city

BackgroundThe Global Lung Function Initiative (GLI-2012) focused on race/ethnicity as an important factor in determining reference values. This study evaluated the effects of changing from Canadian reference equations developed from...

Receptor discordance among primary tumors, brain metastasesand extra-brain metastases in patients with breast cancer.

Background: To investigate the expression status of estrogen receptor(ER), progesterone receptor (PR)and HER2 in patients with breast cancer brain metastases (BM). Methods: Patients who underwent craniotomy for BM were included. The status of ER, PRand HER2 (including HER2-low expression) in primary breast tumors (PT), BM and extra-BM (EM) was determined. Results: Between PT and BM, conversion of hormone receptor and HER2 occurred in 28% (30/107) and 12% (10/86) of cases. When considering three-tiered categorization of HER2, the conversion rate reached 31%. In the paired EM and BM (n=39), the discordance rates were 18%, 3% and 22%, respectively. Conclusion: Receptor discordance was dynamic and relevant, especially using new HER2 categorization.

Age and the cascade impact on coronary flow reserve (CFR) and discordance of fractional flow reserve and non-hyperemic pressure ratios (NHPR).

Key Points CFR decreases with age because hyperemic flow is reduced. Reduced hyperemic flow affects FFR but not NHPR, contributing to a higher rate of discordance between pressure ratios in the elderly. Using a dichotomous age cut off of 60 years, the impact of age in patients with discordant physiologic indices is minimal.

Abstract 174

Objective: To compare concordance/discordance rates in prediction model of 10-year probability of hip and major osteoporoticfractures (MOF) utilizing Fracture Risk Assessment Tool (FRAX) calculations with and withoutbone mineral density (BMD). Furthermore, we aim to characterize difference in various parameters between concordant and discordant groups based on above prediction tool. Method: A retrospective review of patients who underwent BMD measurement and FRAX assessment was conducted. Patients &gt; 40 years were included and FRAX prediction scores were calculated with and without BMD using the FRAX India tool. Subjects were separated on the basis of identical and different treatment recommendations. Fracture risk factors were compared between groups using simple Student’s t test analysis of numerical variables and Fisher’s exact test analysis of binary variables. Results: Out of total 354 subjects, 285 (80.50%) had similar management outcomes with or without BMD in FRAX estimation. The discordant group had a higher mean age (63.1 years; p &lt;0.00024) with similar BMI status. Glucocrticoid use was significantly more prevalent in discordant group (40.5% vs. 27.7%; p &lt;0.03) whereas history of parent hip fracture was more frequent in concordant group (11.6% vs. 2.9%; p &lt;0.03). Conclusion: In most cases, FRAX alone provided the same prediction as FRAX with BMD in fracture prediction models required for management recommendation in majority of cases in our cohort. Older age and priorglucocorticoid use are more frequently seen in discordant group whereas prevalence of parent hip fracture was common in concordant group.

High-fidelity detection, subtyping, and localization of five skin neoplasms using supervised and semi-supervised learning

BackgroundSkin cancers are the most common malignancies diagnosed worldwide. While the early detection and treatment of pre-cancerous and cancerous skin lesions can dramatically improve outcomes, factors such as a global shortage of pathologists, increased workloads, and high rates of diagnostic discordance underscore the need for techniques that improve pathology workflows. Although AI models are now being used to classify lesions from whole slide images (WSIs), diagnostic performance rarely surpasses that of expert pathologists. ObjectivesThe objective of the present study was to create an AI model to detect and classify skin lesions with a higher degree of sensitivity than previously demonstrated, with potential to match and eventually surpass expert pathologists to improve clinical workflows. MethodsWe combined supervised learning (SL) with semi-supervised learning (SSL) to produce an end-to-end multi-level skin detection system that not only detects 5 main types of skin lesions with high sensitivity and specificity, but also subtypes, localizes, and provides margin status to evaluate the proximity of the lesion to non-epidermal margins. The Supervised Training Subset consisted of 2188 random WSIs collected by the PathologyWatch (PW) laboratory between 2013 and 2018, while the Weakly Supervised Subset consisted of 5161 WSIs from daily case specimens. The Validation Set consisted of 250 curated daily case WSIs obtained from the PW tissue archives and included 50 “mimickers”. The Testing Set (3821 WSIs) was composed of non-curated daily case specimens collected from July 20, 2021 to August 20, 2021 from PW laboratories. ResultsThe performance characteristics of our AI model (i.e., Mihm) were assessed retrospectively by running the Testing Set through the Mihm Evaluation Pipeline. Our results show that the sensitivity of Mihm in classifying melanocytic lesions, basal cell carcinoma, and atypical squamous lesions, verruca vulgaris, and seborrheic keratosis was 98.91% (95% CI: 98.27%, 99.55%), 97.24% (95% CI: 96.15%, 98.33%), 95.26% (95% CI: 93.79%, 96.73%), 93.50% (95% CI: 89.14%, 97.86%), and 86.91% (95% CI: 82.13%, 91.69%), respectively. Additionally, our multi-level (i.e., patch-level, ROI-level, and WSI-level) detection algorithm includes a qualitative feature that subtypes lesions, an AI overlay in the front-end digital display that localizes diagnostic ROIs, and reports on margin status by detecting overlap between lesions and non-epidermal tissue margins. ConclusionsOur AI model, developed in collaboration with dermatopathologists, detects 5 skin lesion types with higher sensitivity than previously published AI models, and provides end users with information such as subtyping, localization, and margin status in a front-end digital display. Our end-to-end system has the potential to improve pathology workflows by increasing diagnostic accuracy, expediting the course of patient care, and ultimately improving patient outcomes.

Outcome of Breast Carcinoma between ER, PR with HER-2/Neu Positive Receptor Status

Background: The most frequent kind of cancer among women is breast cancer. Evidence shows that the receptor profile of primary and metastatic breast cancer tissue differs. Archival-paired pathology samples were evaluated to determine the level of hormone receptor discordance. Objective: To evaluate the efficacy of the most frequently used biological indicators in breast cancer for predicting how well a patient would respond to surgical management and their outcome. Materials and Methods: This comparative Study was conducted in the surgery department, Rajshahi Medical College, Bangladesh, with a Matricentred base Study from January 2019 to December 2021. They also included patients (n=100) for whom tissue from either the main or secondary metastatic location was detectable. Cancers were compared and analyzed for their ER, PR, and Her-2/neu status in both the primary and the metastatic. Results: The discordance rate for ER was 17.7% (2-sided p=0.0039), with 9.7% of tumors changing from ER-positive to ER-negative and 8.0% changing from ER-negative to ER-positive. The discordance rate for PR was 37.3% (2-sided p&lt;0.0001), with Each and every one of these tumors going through a transition from PR-positive to PR-negative. As far as Her-2/neu is concerned, no major discrepancies were discovered. Conclusions: Hormone receptor status is significantly different between primary and metastatic breast cancer samples, as suggested by this dataset. Common instances of PR decline were observed. More than half of the patients had a positive hormone status, and it was found that the illness had spread to other organs in most of these cases.

Significance of the Pee-Value: Relevance of Urine Studies for Patients with Myeloma Undergoing Transplantation

INTRODUCTION: International Myeloma Working Group (IMWG) criteria require 24-hour urine specimens as part of response assessments, which can be cumbersome for patients to collect. This requirement is particularly onerous before autologous stem cell transplantation (ASCT), a period relatively soon after diagnosis with many concurrent testing requirements. The necessity of urine testing to complete response (CR) determinations and its prognostic impact on progression-free survival (PFS) have been questioned in subgroup analyses of clinical trials (Dejoie 2016; Lahuerta 2019). However, the real-world importance of urine testing to IMWG response criteria more broadly has not been ascertained. METHODS: We analyzed all patients with multiple myeloma (MM), excluding those with oligosecretory disease or progressive disease during induction, who underwent first ASCT at our institution between 2016-2019. Patients with measurable serum M-protein (>1 g/dL) and light-chain (LC)-only disease were included. Patients with missing diagnostic or pre-ASCT data precluding IMWG response assessments were excluded. Evaluable urine studies were defined as a documented urine immunofixation (UIFE) value or, if UIFE was missing, a presumptive +UIFE if urine protein electrophoresis showed a paraprotein. For patients with a documented negative UIFE at diagnosis, -UIFE was presumed if urine studies were not repeated before ASCT. For patients with evaluable baseline and pre-ASCT urine testing, we assessed responses using both traditional IMWG criteria and 'urine-free’ IMWG criteria, whereby urine testing results were systematically removed as options or requirements to achieve any given response depth. We hypothesized that urine-free criteria would yield discordant responses in <10% of patients, a proportion we determined a priori to be clinically irrelevant. RESULTS: Of 347 screened patients, 66 (19%) were excluded due to missing data precluding pre-ASCT response assessments by traditional IMWG criteria. Compared to patients (n=281) with sufficient data, these 66 excluded patients were more likely to have LC-only disease and to have been transplanted before 2018. Of 281 patients evaluable for responses by both traditional and urine-free IMWG criteria, 11 patients (4%) had discordant responses (Figure 1). Discordance rates were 14% (9/63) among patients with LC-only disease and 1% (2/218) among patients with measurable serum M-proteins. Of these 11 discordant responses, 7 were superior with urine-free criteria while 4 were inferior (Table 1). DISCUSSION: In our retrospective study, response depths changed in only 4% of patients when urine requirements were systematically removed from IMWG criteria. Rates of discordance varied by paraprotein biology: 1% of patients with a measurable serum M-protein had discordant responses, versus 14% of patients with LC-only disease. This calls into question the common practice of requiring repeat 24-hour urine assessments for all patients prior to ASCT, since its utility may be practically limited to patients with LC-only disease. Interestingly, omitting urine from IMWG response criteria did not uniformly shift responses in either direction. Limitations of our data include missing data in 66 patients (who had predominantly LC-only disease) as well as lack of generalizability to ASCT-ineligible patients. However, our study is important in demonstrating that 24-hour pre-ASCT urine testing may be unnecessary for many patients with MM, particularly those with a measurable serum M-protein at diagnosis. Further research is needed to assess whether urine-free or traditional response criteria better reflect underlying disease biology in terms of their ability to prognosticate PFS. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comparison of 22C3-PD-L1 Expression Between Paired Tumor Paraffin Blocks of Surgical Resection Specimens of Nonsmall Cell Lung Cancer.

In this study, our aim was to evaluate the discordance of programmed cell death ligand 1 (PD-L1) expression between 2 paired paraffin blocks from surgical nonsmall cell lung cancer (NSCLC) specimens, thus providing recommendations for choosing paraffin blocks for PD-L1 immunohistochemistry detection. A total of 460 paired paraffin blocks of surgical NSCLC specimens were analyzed using the 22C3-PD-L1 assay. PD-L1 expression between 2 paired paraffin blocks was calculated using 3 classification schemes, tumor proportion score (TPS)-based 3-level classification and TPS-based binary classification using TPS ≥1% or TPS ≥50% as the cutoff. Clinicopathological characteristics were analyzed for cases with discordant PD-L1 expression. PD-L1 expression in 2 paired paraffin blocks of surgical NSCLC specimens was highly correlated from a single tumor ( R2 =0.89) in the overall trend. The overall discordance rates were 10.9%, 7.4%, and 3.5% respectively when using TPS-based 3-level classification or binary classification. No statistical differences were observed in PD-L1 expression discordance rates when patients were stratified by age, sex, smoking status, histologic types, TNM stage, or years of paraffin blocks ( P >0.05). The presence of a solid histologic pattern was associated with a higher PD-L1 expression discordance rate in adenocarcinomas ( P <0.05). Twenty-five cases with discordant PD-L1 expression were divided into 2 categories: spatial heterogeneity without recognizable morphology difference (76%) and spatial heterogeneity with significantly different morphology (24%). The discordance rate in TPS scores was much higher in cases with different morphology than those without different morphology. One representative paraffin block containing adequate neoplastic tissue may be adequate to determine PD-L1 expression in most of the surgical specimens of NSCLC. In cases that harbored different morphology in different paraffin blocks, the dual-block immunohistochemistry assessment method is recommended due to the intratumoral heterogeneity.

Unnecessary radiation exposure during diagnostic radiography in infants in a neonatal intensive care unit: a retrospective cohort study

Unnecessary radiation exposure (URE) during radiographic examination is an issue among infants in neonatal intensive care units (NICUs). The causes of URE have not been fully explored. This study investigated the incidence and identified the causes of URE in infants during diagnostic radiography in a NICU. This was a retrospective cohort study. We retrieved and analysed requests and radiographs taken at a tertiary NICU between September and November 2018. URE was defined as the rate of discordance between requests and images taken (DisBRI) and unnecessary radiation exposure in irrelevant regions (UREIR) during radiography. We compared the rates of URE between very low-birth-weight (VLBW, birth weight < 1500 g) infants and non-VLBW infants. A total of 306 radiographs from 88 infants were taken. The means ± standard deviations (SDs) of gestational age and birth weight were 35.7 ± 3.6 weeks and 2471 ± 816 g, respectively. Each infant underwent an average of 3.5 radiographs. The DisBRI rate was 1.3% and was mostly related to poor adherence to requests. The UREIR rates in thoraco-abdominal babygrams were 89.6% for the head, 14.8% for the elbows and 18.4% for the knee and were mainly related to improper positioning of and collimation in infants while performing radiography. The UREIR rates for the head, knee and ankle were higher in VLBW infants than in non-VLBW infants (94.6% vs. 85.6%, 27.0% vs. 11.5% and 5.4% vs. 0.7%, respectively, p < 0.05).Conclusions: URE during diagnostic radiography is common in sick infants and is mainly related to improper positioning and collimation during examinations. Adherence to protocols when performing radiographic examination or using ultrasonography may be a solution to reduce URE in infants in NICUs.What is Known:• The risk of unnecessary radiation exposure (URE) during radiography has been a common and important issue in sick infants in neonatal intensive care units (NICUs).• The new point-of-care ultrasound (POCUS) technique decreases the need for chest films and prevents radiation exposure in neonates.What is New:• In the NICU, URE is still a common issue in critically ill infants during radiographic examinations. The causes of URE during diagnostic radiography are mainly due to improper positioning and collimation during examinations.• The incidence of URE in irrelevant regions is higher in very low-birth-weight (VLBW) infants than in non-VLBW infants.

The incidence burden of unreported pedestrian crashes in Illinois

Objective Communities with high rates of pedestrians struck by motor vehicles may miss out on mitigation resources and suffer worse medical outcomes if crashes there go unreported to police. This study investigates the places, people, and communities in Illinois where struck pedestrians are most likely to go unreported. A better understanding of the true burden and distribution of struck pedestrians will help guide policy and direct investments and interventions where they are most needed. Methods Hospital records of pedestrians treated for injuries sustained by a motor vehicle that were not able to be linked with a corresponding crash report across three consecutive years are investigated. Discordance rates of struck pedestrians are calculated and disaggregated by region. A presentation of summary statistics is accompanied by an ordinary least squares predictive model to estimate the relationship between discordant struck pedestrians and sociodemographic factors. Results The incidence of unreported struck pedestrians was not randomly distributed. Blacks struck by a motor vehicle were disproportionately likely to go unreported to police. Zip codes with the most unreported crashes per capita on average had double the poverty rate and 2.6 times the carless household rate as the rest of Illinois. Struck pedestrians diagnosed at the hospital with an intoxicating substance went unreported to police nearly 70% of the time. Generally, more severe head and thorax injuries were more likely to be reported. Struck pedestrians outside of Cook County averaged a 60% discordance rate, those within Cook County averaged a discordance rate of about 50%. Struck pedestrian cases reported to police averaged emergency department charges of about $2,500 more than unreported cases. Conclusions Underlying and contributing factors influential of a struck pedestrian's decision of whether to report to police is complex and layered by social constructs mixed with difficult economic decisions, often further complicated by the fog of impairment. Recommendations are made for community outreach to stress the importance of reporting incidents to police, along with adjusting case count numbers in police records using hospital data and discordance rates.

Trust but Verify: Discordance in Opioid Reporting Between the Electronic Medical Record and a Statewide Database.

The electronic medical record (EMR) is often used as the primary source for patient medication lists and history. We sought to determine the accuracy of the EMR in documenting opioid prescriptions in patients undergoing fracture repair compared to a statewide database. This retrospective study was conducted at an urban level 1 trauma center. Patients > 18 years old were included if they were admitted directly through the emergency room with isolated single orthopedic injuries. Opioid use and prescription data prior to admission and three months following surgery were collected through the EMR and a California statewide database of controlled substance prescriptions. A 2 x 2 McNemar's test was used to identify discordance between the EMR and Controlled Substance Utilization Review and Evaluation System (CURES). A total of 369 patients were included. The EMR reported that 143 patients had an opioid prescription within 30 days prior to admissioncompared to 75 patients reported by CURES (discordance rate [DR]: 34.7%) (p < 0.001). Between postoperative days (POD) 0-30, the EMR reported that 367 patients had an opioid prescriptioncompared to 285 reported by CURES (DR: 22.8%) (p < 0.001). Between POD 30-60, the EMR reported that 142 patients had an opioid prescriptioncompared to 84 reported by CURES (DR: 34.7%) (p < 0.001). Between POD 60-90, the EMR reported that 83 patients had an active opioid prescriptioncompared to 60 patients reported by CURES (DR: 41.0%) (p = 0.10). There is a significant discordance between the databases in documenting opioid use. Physicians should check multiple sources to best assess active opioid prescriptions.

Evaluation of the Nigeria national HIV rapid testing algorithm.

Human Immunodeficiency Virus (HIV) diagnosis remains the gateway to HIV care and treatment. However, due to changes in HIV prevalence and testing coverage across different geopolitical zones, it is crucial to evaluate the national HIV testing algorithm as false positivity due to low prevalence could be detrimental to both the client and the service delivery. Therefore, we evaluated the performance of the national HIV rapid testing algorithm using specimens collected from multiple HIV testing services (HTS) sites and compared the results from different HIV prevalence levels across the six geopolitical zones of Nigeria. The evaluation employed a dual approach, retrospective, and prospective. The retrospective evaluation focused on a desktop review of program data (n = 492,880) collated from patients attending routine HTS from six geopolitical zones of Nigeria between January 2017 and December 2019. The prospective component utilized samples (n = 2,895) collected from the field at the HTS and tested using the current national serial HIV rapid testing algorithm. These samples were transported to the National Reference Laboratory (NRL), Abuja, and were re-tested using the national HIV rapid testing algorithm and HIV-1/2 supplementary assays (Geenius to confirm positives and resolve discordance and multiplex assay). The retrospective component of the study revealed that the overall proportion of HIV positives, based on the selected areas, was 5.7% (28,319/492,880) within the study period, and the discordant rate between tests 1 and 2 was 1.1%. The prospective component of the study indicated no significant differences between the test performed at the field using the national HIV rapid testing algorithm and the re-testing performed at the NRL. The comparison between the test performed at the field using the national HIV rapid testing algorithm and Geenius HIV-1/2 supplementary assay showed an agreement rate of 95.2%, while that of the NRL was 99.3%. In addition, the comparison of the field results with HIV multiplex assay indicated a sensitivity of 96.6%, the specificity of 98.2%, PPV of 97.0%, and Kappa Statistic of 0.95, and that of the NRL with HIV multiplex assay was 99.2%, 99.4%, 99.0%, and 0.99, respectively. Results show that the Nigeria national serial HIV rapid testing algorithm performed very well across the target settings. However, the algorithm's performance in the field was lower than the performance outcomes under a controlled environment in the NRL. There is a need to target testers in the field for routine continuous quality improvement implementation, including refresher trainings as necessary.

CHEMOTHERAPY INDUCED HISTOPATHOLOGICAL CHANGES IN MASTECTOMY SPECIMENS - STUDY AT A TERTIARY CARE CENTRE

Background: Pathological complete response (pCR) to Neo adjuvant chemotherapy (NACT) is a signicant prognostic marker in breast cancer, so accurate diagnosis and grading of pathological chemo response of tumour is needed for an effective planning of treatment regimen. To study the various histopathological Aims: changes in Mastectomy specimens following NACT and to evaluate the pathological response of tumour to NACT, also to compare the expression of ER, PR, and HER2 in biopsies and post NACT mastectomy specimens by Immunohistochemistry (IHC). Methods And Materials: 50 breast carcinoma cases, who was diagnosed on trucut biopsies and treated with preoperative NACT followed by mastectomy was included. In post NACT mastectomy specimens, the chemoresponse was classied according to Union for International Cancer Control (UICC) guidelines. ER, PR, and HER2/ neu receptor expression was compared between trucut biopsy specimens (pre- NACT) and resection specimens (post- NACT). Results were analysed by Chi square test and McNemar chi square test. Among 50 cases, patients presented with lump, Results: involved more on the right and in upper outer quadrant. Most common stage at presentation is stage III A. Histologically all belong to IDCC -NST histological subtype. Signicant reduction in mean tumour size by 52.7% after NACT was observed. pCR, pPR and pNR was observed in 20 %, 58 % and 22 %of the cases respectively. Most common histological change seen in post NACT is necrosis, desmoplasia, brosis, lymphocytic inammatory response. Discordance in ER expression (17.5 %), PR expression (20%) and HER2 /neu (12.5 %) before and after NACT. But these were statistically insignicant. CONCLUSIONS: Pathological evaluation of chemo response of tumour is the gold standard. The discordance rate of ER, PR and HER-2/neu expression following NACT was statistically insignicant, larger studies needed to analyse their impact in patient management.

Combining the GP's assessment and the PHQ-9 questionnaire leads to more reliable and clinically relevant diagnoses in primary care.

Screening questionnaires are not sufficient to improve diagnostic quality of depression in primary care. The additional consideration of the general practitioner's (GP's) assessment could improve the accuracy of depression diagnosis. The aim of this study was to examine whether the GP rating supports a reliable depression diagnosis indicated by the PHQ-9 over a period of three months. We performed a secondary data analysis from a previous study. PHQ-9 scores of primary care patients were collected at the time of recruitment (t1) and during a follow-up 3 months later (t2). At t1 GPs independently made a subjective assessment whether they considered the patient depressive (yes/no). Two corresponding groups with concordant and discordant PHQ-9 and GP ratings at t1 were defined. Reliability of the PHQ-9 results at t1 and t2 was assessed within these groups and within the entire sample by Cohen's Kappa, Pearson's correlation coefficient and Bland-Altman plots. 364 consecutive patients from 12 practices in the region of Upper Bavaria/Germany participated in this longitudinal study. 279 patients (76.6%) sent back the questionnaire at t2. Concordance of GP rating and PHQ-9 at t1 led to higher replicability of PHQ-9 results between t1 and t2. The reliability of PHQ-9 was higher in the concordant subgroup (κ = 0.507) compared to the discordant subgroup (κ = 0.211) (p = 0.064). The Bland-Altman Plot showed that the deviation of PHQ-9 scores at t1 and t2 decreased by about 15% in the concordant subgroup. Pearson's correlation coefficient between PHQ-9 scores at t1 and t2 increased significantly if the GP rating was concordant with the PHQ-9 at t1 (r = 0.671) compared to the discordant subgroup (r = 0.462) (p = 0.044). The combination of PHQ-9 and GP rating might improve diagnostic decision making regarding depression in general practices. PHQ-9 positive results might be more reliable and accurate, when a concordant GP rating is considered.

Use of Anatomic Radiographic Horizons for the Lateral Center-Edge Angle in the Classification of Hip Dysplasia

Background: The lateral center-edge angle of Wiberg (LCEA) and Tönnis angle (TA) rely on a “horizon” that functions as a reference point for measurements of hip dysplasia on weightbearing anteroposterior pelvis radiographs. There are 3 different horizons that are currently utilized depending on surgeon preference: (1) a line parallel to the radiographic floor (F), (2) a line that connects the inferior portions of the acetabular teardrops (ATs), or (3) a line that connects the ischial tuberosities (ITs). It is imperative to accurately assess the degree of hip dysplasia on initial workup to select the appropriate surgical intervention. Purpose: To assess how the choice of a radiographic horizon affects the measurements of the LCEA and TA. The secondary purpose was to assess how the horizon affected the classification of hips as either normal, borderline dysplastic, or dysplastic. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: The LCEA and TA were measured on all preoperative weightbearing anteroposterior pelvis radiographs for 186 consecutive patients who underwent hip preservation surgery between February 2016 and November 2020 (140 hip arthroscopic procedures, 46 combined hip arthroscopic procedures with periacetabular osteotomy), 3 times per hip, each time using an F, AT, and IT horizon. The Student t test was used to analyze the differences in the measurements of the LCEA and TA, and discordance rates in the dysplasia classification between horizons were quantified. Results: For the entire study population, the mean LCEAF (23.4°± 7.4°) was significantly greater than the mean LCEAIT (23.1°± 7.2°) (95% CI, −0.634 to −0.003; P = .047) and mean LCEAAT (23.0°± 7.1°) (95% CI, −0.723 to −0.139; P = .004). There was no difference between the LCEAIT and LCEAAT (95% CI, −0.305 to 0.080; P = .251). When stratified by hip arthroscopic surgery, the mean LCEAF (26.3°± 5.6°) was significantly greater than the mean LCEAAT (25.8°± 5.3°) (95% CI, −0.845 to −0.162; P = .004). Overall, there was a 17.7% and 18.3% discordance rate in the dysplasia classification using the LCEAIT and LCEAAT compared with the LCEAF, respectively. There were no statistically significant differences between the mean TAIT, TAAT, and TAF for the entire study population, the arthroscopic surgery group, and the combined arthroscopic surgery and periacetabular osteotomy group. Conclusion: There was no statistical difference between the AT and IT horizons for LCEA measurements. The dysplasia classification was in better agreement between the 2 anatomic horizons compared with the F horizon. The TA was not affected by changes in the horizon.

Chemoradiation therapy alters the PD-L1 score in locoregional recurrent squamous cell carcinomas of the head and neck

PD-L1 testing guides therapeutic decision-making for head and neck squamous cell carcinoma (HNSCC). We sought to understand whether chemoradiation therapy (CRT) influences the PD-L1 combined positive score (CPS) and other biomarkers of response to immunotherapy. PD-L1 expression was assessed using immunohistochemistry, and bulk RNA sequencing was performed on 146 HNSCC patients (65 primary sites, 50 paired local recurrences, and 31 paired regional recurrences). PD-L1 was scored using the CPS of ≥1, ≥20, and ≥50. Overall, 98 %, 54 %, and 17 % of HNSCCs had a CPS ≥1, ≥20, and ≥50, respectively. When using a cut-off of ≥1, CRT did not significantly change CPS at the locoregional recurrent site. However, there were significant changes when using CPS ≥20 or ≥50. The CPS changed for 32 % of patients when using a CPS ≥20 (p < 0.001). When using a CPS ≥50, there was a 20–23 % (p = 0.0058–0.00067) discordance rate at the site of locoregional recurrence. Oral cavity cancers had a significantly higher discordant rate than other primary sites for CPS ≥50, 44 % (8/18, p = 0.0058) and 58 % (7/12, p = 0.00067) discordance at the site of local and regional recurrence, respectively. When evaluating the 18 gene IFN-ɣ signature predictive of response to anti-PD-1 blockade, there was a statistically significant increase in the IFN-ɣ signature in recurrent larynx cancer (p = 0.02). Our study demonstrates that when using a higher cut-off of CPS ≥20 and ≥50, a repeat biopsy may be warranted after CRT for local and regional recurrent HNSCCs.

A Quantitative and Qualitative Assessment of Frozen Section Diagnosis Accuracy and Deferral Rate Across Organ Systems.

Monitoring of frozen section diagnostic performance provides an important quality improvement measure. Surgical specimens involving a frozen section diagnosis over a 3-year period were retrospectively reviewed. Glass slides were reviewed on cases with discordance. Discordance and deferral rates were calculated. Of 3,675 frozen section diagnoses included, 96 (2.7%) were discordant with the final diagnosis. Additionally, 114 frozen section diagnoses (3.1%) were deferred. The organ-specific discordance rates were lowest in breast and genitourinary specimens and highest for pancreas, lymph node, and gynecologic specimens. Deferral rates were highest in musculoskeletal, breast, and hepatobiliary cases and lowest in thyroid, parathyroid, and neuropathology cases. Discordance was explained by block-sampling error (45%), specimen-sampling error (27%), or interpretation error (27%). Discordant frozen section diagnoses from gynecologic specimens were responsible for 81% of specimen-sampling errors; frozen section diagnoses of lymph nodes, head and neck, and pancreas were responsible for 54% of interpretation errors; 51% of block-sampling errors involved lymph node evaluation for metastatic carcinoma. Careful gross evaluation and microscopic examination of multiple levels should minimize specimen-sampling error and block-sampling error, respectively. Periodic review of accuracy and deferral rates may help reduce errors and improve the overall performance of this essential procedure.

P003: A retrospective study to evaluate the reliability of staging and risk stratification of adolescent and adult patients with Hodgkin’s lymphoma registered in the lymphoma clinic at Tata Memorial Centre.

Table 1: Baseline characteristics Purpose: Risk stratification is a key factor,which depends on staging, clinical and laboratory parameters in determining the treatment in Hodgkin’s lymphoma (HL). However, this is highly prone to erroneous results due to overlapping components in the staging systems and inter-observer variability.We conducted this study to assess the reliability of risk stratification performed by our clinicians at our busy multidisciplinary clinic (MDC). Methods: A retrospective analysisof newly diagnosed HL patients from the multidisciplinary clinic database for the year 2016-18was conducted.All patients underwent an 18-FDG PET/CT scan and other evaluations as per our institutional checklist. The reliability of staging and risk stratification done during the MDC was compared with a team of independent experts (medical oncology, radiation oncology and nuclear medicine) based on a standard reference. The concordance testing was done using kappa statistic for agreement (≥ 0.8 as perfect agreement) andP <0.05 was considered significant. Results: 120 patients were analyzed, and the baseline characteristics are described in Table 1. The patients initially underwent staging by MDC and were risk stratified into early favorable (16 patients [13.5%]), early unfavorable (29 patients [24%]) and advanced (75 patients [62.5%]). A discordance rate of 10% (12 patients) was observed in disease staging and 8.3% in risk stratification (10 patients) between the MDC and the expert team. All deviations were due to up-staging of patients by MDC, of which 9 patients in early favorable were misclassified as early unfavorable and 1 patient as advanced from early unfavorable. This resulted in 10 patients receiving higher dose of chemotherapy and radiation. However, no patients were under treated. On completion of treatment, 82%of patientshadcomplete response, 12%had partial responseand 5%had disease progression. Our results show that the discordance rates were not significantbetween the independent reviewers and MDC team with kappa score of 0.859 for stagingand 0.847 for risk stratification. Conclusion: Despite our busy setting, the risk stratification was found to be reliable and comparable to reference standards. One reason for this would be the involvement of a multidisciplinary team in our lymphoma clinic. Yet, 8% of the patients received a more intense therapy than needed, demonstrating the need for a simpler, objective and technology driven risk stratification process.