Nuclear Grade Research Articles

Reliability of assessing morphologic features with prognostic significance in cytology specimens of epithelioid diffuse pleural mesothelioma and implications for cytopathology reporting.

The World Health Organization incorporates morphologic features with prognostic significance in the 2021 classification of epithelioid diffuse pleural mesothelioma (E-DPM). Although cytology specimens are often the first and occasionally the only specimen available for patients with DPM, these features have not yet been investigated in cytology. Nuclear atypia, pleomorphic features, necrosis, and architectural patterns were retrospectively assessed in 35 paired cytology and concurrent/consecutive surgical pathology specimens of E-DPM. Agreement between pairs was determined via unweighted κ scores. Discordant cases were re-reviewed to determine the reasons for disagreement. Interpretation of nuclear atypia in cytology was concordant with histology in all cases (κ=1.000; p<.001). The presence of pleomorphic features and necrosis was concordant in 97.1% (κ=0.842; p<.001) and 85.7% (κ=0.481; p=.001) of paired cases, respectively. Assessment of architectural patterns in cytology showed only slight agreement with histology (κ=0.127; p=.037). In cytology cases (n=23) with cell block material available, assessment of nuclear atypia and the presence of pleomorphic features showed perfect agreement (κ=1.000; p<.001, each), the presence of necrosis showed moderate agreement (κ=0.465; p=.008), and assessment of architectural patterns showed slight agreement (κ=0.162; p=.15) in paired specimens. Most disagreements were due to sampling differences between cytology and histology specimens. Although complete nuclear grading of E-DPM is not possible given the unreliability of mitotic counts in cytology, assessment of nuclear atypia in cytology specimens is shown to be reliable. Identification of pleomorphic features and necrosis is also reliable despite occasional sampling issues. Assessment of architectural patterns is more limited in cytology.

Mechanistic study of incipient corrosion for nuclear grade lean-Cr FeCrAl alloys in a simulated PWR environment

This study systematically investigated the incipient corrosion behavior of Fe-13Cr-4.5Al (wt%) and lean-Cr (7–10 wt%) with 5Al (wt%) FeCrAl alloy with a timescale of 4 months under simulated PWR conditions (18.6 MPa and 360 °C) in an autoclave system. The corrosion induced two types of structure of oxide scale. FeCrAl alloys corroded for 3 months exhibited a duplex structure containing outer oxide particles and an inner Cr-rich spinel. During the corrosion test lasting 3–4 months, a triplex structure containing outer oxide particles, an inner compact Cr-rich spinel layer, and a porous spinel layer was observed. Moreover, Cr enriched at the periphery of outer oxides, indicating the formation of FeCr2O4 spinel oxide.

Oncologic Outcomes and Predictors in Patients with Stage PT3aNxM0 Renal Cell Carcinoma Following Radical Nephrectomy.

The objective of this study is to evaluate oncologic outcomes in patients with PT3aNxM0 renal cell carcinoma following radical nephrectomy and also to investigate these outcomes in each specific subgroup of PT3a renal cell carcinoma and to determine predictive factors of recurrence, metastasis, and mortality. In this retrospective cohort study, we included 94 patients with stage PT3a renal cell carcinoma who had undergone radical nephrectomy from 2011 to 2016. All patients who had survived had at least 60 months of follow-up. Demographic and clinical data were collected; univariable and multivariable Cox proportional hazards regression analysis was performed to identify predictors of metastasis, recurrence, and cancer-related mortality. Patients' mean age was 58.07 ± 11.17 years and 62/94 (65.9%) were male. The mean follow-up time was 48.1 ± 25.5 months. Forty-three patients (45.7%) had experienced cancer-related mortality. The mean cancer-specific survival time was 60.94 months and the mean metastasis-free and local recurrence-free survival times were 57.06 and 88.72 months, respectively. Metastasis and local recurrence had occurred in 42 (44.6%) and 4 (4.25%) patients, respectively. After performing multivariate analysis, higher nuclear Fuhrman's grade (P < .001) and simultaneous involvement of the renal vein and perinephric fat (P < .001) were found to be predictive of cancerrelated mortality. Advanced nuclear Fuhrman's grade was the only independent predictor of metastasis (P=.001). Based on our results, advanced nuclear Fuhrman's grade and sarcomatoid change can independently predict mortality in patients with stage PT3aNxM0 renal cell carcinoma. Close monitoring during the follow-up period is recommended in patients with the mentioned risk factors.

Quantitative Nuclear Grading: An Objective, Artificial Intelligence–Facilitated Foundation for Grading Noninvasive Papillary Urothelial Carcinoma

In nonmuscle invasive bladder cancer, grade drives important treatment and management decisions. However, grading is complex and qualitative, and it has considerable interobserver and intraobserver variability. Previous literature showed that nuclear features quantitatively differ between bladder cancer grades, but these studies were limited in size and scope. In this study, we aimed to measure morphometric features relevant to grading criteria and build simplified classification models that objectively distinguish between the grades of noninvasive papillary urothelial carcinoma (NPUC). We analyzed 516 low-grade and 125 high-grade 1.0-mm diameter image samples from a cohort of 371 NPUC cases. All images underwent World Health Organization/International Society of Urological Pathology 2004 consensus pathologist grading at our institution that was subsequently validated by expert genitourinary pathologists from 2 additional institutions. Automated software segmented the tissue regions and measured the nuclear features of size, shape, and mitotic rate for millions of nuclei. Then, we analyzed differences between grades and constructed classification models, which had accuracies up to 88% and areas under the curve as high as 0.94. Variation in the nuclear area was the best univariate discriminator and was prioritized, along with the mitotic index, in the top-performing classifiers. Adding shape-related variables improved accuracy further. These findings indicate that nuclear morphometry and automated mitotic figure counts can be used to objectively differentiate between grades of NPUC. Future efforts will adapt the workflow to whole slides and tune grading thresholds to best reflect time to recurrence and progression. Defining these essential quantitative elements of grading has the potential to revolutionize pathologic assessment and provide a starting point from which to improve the prognostic utility of grade.

PD40-06 COMPARING ONCOLOGIC OUTCOMES BETWEEN SURGERY AND MICROWAVE ABLATION FOR RENAL MASSES BETWEEN 3 AND 7 CM

You have accessJournal of UrologyCME1 Apr 2023PD40-06 COMPARING ONCOLOGIC OUTCOMES BETWEEN SURGERY AND MICROWAVE ABLATION FOR RENAL MASSES BETWEEN 3 AND 7 CM Arighno Das, Daniel Shapiro, Tudor Borza, Shane Wells, Louis Hinshaw, Timothy Ziemlewicz, Paul Laeseke, Fred Lee, Stephen Nakada, and E. Jason Abel Arighno DasArighno Das More articles by this author , Daniel ShapiroDaniel Shapiro More articles by this author , Tudor BorzaTudor Borza More articles by this author , Shane WellsShane Wells More articles by this author , Louis HinshawLouis Hinshaw More articles by this author , Timothy ZiemlewiczTimothy Ziemlewicz More articles by this author , Paul LaesekePaul Laeseke More articles by this author , Fred LeeFred Lee More articles by this author , Stephen NakadaStephen Nakada More articles by this author , and E. Jason AbelE. Jason Abel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003345.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Current AUA guidelines recommend radiofrequency ablation (RFA) or cryoablation be considered only for renal masses <3 cm. However, microwave ablation (MWA) reliably generates larger ablation zones compared to other ablation modalities. This study compared oncologic outcomes between surgery and MWA in patients with renal masses between 3 and 7 cm. METHODS: Data was analyzed for consecutive patients with 3 to 7 cm renal cell carcinoma (RCC) treated with MWA, radical nephrectomy (RN), or partial nephrectomy (PN), excluding patients with metastases or tumor thrombus. Local recurrence-free, metastasis-free, and cancer-specific survival were estimated using Kaplan-Meier method. Variables associated with survival were determined using Cox proportional hazard models. RESULTS: Of 732 patients, 160 (22%) underwent MWA, 184 (25%) underwent PN, and 392 (53%) underwent RN (Table 1). Patients treated with MWA were older and more comorbid (p<0.001). Patients who underwent RN had larger tumors (p<0.001) and higher nuclear grade (p<0.001). Median follow-up was 40, 41, and 44 months following MWA, PN, and RN (p=0.4). 5-year local recurrence free survival was lower for MWA (86%) compared to PN (98%) and RN (98%) (p<0.0001). No differences were noted in metastasis-free or cancer-specific survival between the three cohorts (p=0.13 and p=0.85). Adjusting for age, pathology, radiologic size, and nuclear grade, MWA was associated with similar metastasis-free and cancer-specific survival compared to surgery (Table 2).Of 18 patients with local recurrence following MWA (11%), 13 underwent repeat ablation, 3 pursued surveillance, 1 had stereotactic radiation, and 1 underwent nephrectomy. After 2nd ablation, 12/13 (92%) patients had no recurrence of disease at median 19 months. CONCLUSIONS: Microwave ablation for 3 to 7 cm renal cell cancer has higher rates of local recurrence, which may be salvaged by repeat treatment. There was no difference in metastatic progression or cancer specific survival compared to surgery. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1053 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Arighno Das More articles by this author Daniel Shapiro More articles by this author Tudor Borza More articles by this author Shane Wells More articles by this author Louis Hinshaw More articles by this author Timothy Ziemlewicz More articles by this author Paul Laeseke More articles by this author Fred Lee More articles by this author Stephen Nakada More articles by this author E. Jason Abel More articles by this author Expand All Advertisement PDF downloadLoading ...

Microstructural characterization of the CGB graphite grade from the molten salt reactor experiment

In the 1960s, the Molten Salt Reactor Experiment demonstrated the feasibility of molten salt reactors for civil applications. The Molten Salt Reactor Experiment used a nuclear graphite grade known as CGB in the core as the fast neutron moderator. For application in this purpose, CGB graphite underwent additional impregnation steps that are not typically used in conventional nuclear graphites. These additional impregnations significantly lowered the permeability and reduced the size of pore openings in CGB graphite, for the purpose of inhibiting molten salt ingression into the graphite. Although several publications report the mechanical properties and irradiation response of CGB graphite, little information has been published about the microstructure or sealant used for this graphite grade. Here the results of multiple advanced microscopy techniques are presented with the objective to investigate the unique microstructure and sealing technology of legacy material from the Molten Salt Reactor Experiment so it can be potentially readopted for modern reactors. The microstructural characterization shows that some pores were fully sealed by the impregnation whereas other regions contained foam-like materials that partially filled the void content. This manuscript also investigates and documents the nature and possible source of the sealant material. The pore sealing methods used for CGB are discussed and compared with other common technologies used to reduce the impregnation of molten salts into graphite components. Knowledge of CGB graphite's microstructure can enable development of new pore infiltration technologies to improve in operando behavior advancing the next generation of molten salt reactors.

The Prognostic Significance of Body Mass Index in Patients Undergoing Nephrectomy for Nonmetastatic Renal Cell Carcinoma

Purpose: The aim of this study was to evaluate the impact of body mass index (BMI) on survival in patients with nonmetastatic renal cell carcinoma (RCC) treated with radical or partial nephrectomy.Materials and Methods: Between June 1994 and December 2021, 482 patients with RCC underwent radical or partial nephrectomy. Among those patients, 21 patients with lymph node or distant metastasis were excluded. The medical records of the remaining 461 patients were retrospectively reviewed. The prognostic significance of various clinicopathological variables, including BMI, was evaluated in univariate and multivariate analyses.Results: Of the total 461 patients, 171 (37.1%) were categorized as normal-weight, 118 (25.6%) as overweight, and 172 (37.3%) as obese. Forty-eight patients (10.4%) developed local recurrence or distant metastasis, and 26 patients (5.6%) died from the disease during the follow-up period. In the multivariate analysis, BMI (p=0.017), tumor size (p&lt;0.001), T stage (p&lt;0.001), Fuhrman nuclear grade (p=0.016), and lymphovascular invasion (p=0.012) were independent predictors of recurrence-free survival. Furthermore, BMI (p=0.025), tumor size (p&lt;0.001), T stage (p&lt;0.001), Fuhrman nuclear grade (p=0.047), and lymphovascular invasion (p=0.033) were independent predictors of cancer-specific survival.Conclusions: Our results suggest that overweight and obese patients with nonmetastatic RCC treated with radical or partial nephrectomy have a more favorable prognosis. These findings indicate that BMI could be an important factor for predicting recurrence or survival in patients undergoing nephrectomy for nonmetastatic RCC.

Efficacy of partial nephrectomy in patients with localized renal carcinoma: a 20-year experience of 2 046 patients in a single center

Objectives: To analyze the long-term survival of patients with localized renal cell carcinoma after partical nephrectomy. Methods: The clinicopathological records and survival follow-up data of 2 046 patients with localized renal cell carcinoma, who were treated with partial nephrectomy from August 2001 to February 2021 in the Department of Urology, Sun Yat-sen University Cancer Center, were retrospectively analyzed. There were 1 402 males and 644 females, aged (M(IQR)) 51 (19) years (range: 6 to 86 years). The primary end point of this study was cancer-specific survival. Survival curves were estimated using the Kaplan-Meier method, and the difference test was performed by Log-rank test. Univariate and multivariate Cox analysis were fitted to determine factors associated with cancer-specific survival. Results: The follow-up time was 49.2 (48.0) months (range: 1 to 229 months), with 1 974 patients surviving and 72 dying. The median cancer-specific survival time has not yet been reached. The 5- and 10-year cancer specific survival rates were 97.0% and 91.2%, respectively. The 10-year cancer-specific survival rates for stage pT1a (n=1 447), pT1b (n=523) and pT2 (n=58) were 95.3%, 81.8%, and 81.7%, respectively. The 10-year cancer-specific survival rates of patients with nuclear grade 1 (n=226), 2 (n=1 244) and 3 to 4 (n=278) were 96.6%, 89.4%, and 85.5%, respectively. There were no significant differences in 5-year cancer-specific survival rates among patients underwent open, laparoscopic, or robotic surgery (96.7% vs. 97.1% vs. 97.5%, P=0.600). Multivariate analysis showed that age≥50 years (HR=3.93, 95%CI: 1.82 to 8.47, P<0.01), T stage (T1b vs. T1a: HR=3.31, 95%CI: 1.83 to 5.99, P<0.01; T2+T3 vs. T1a: HR=2.88, 95%CI: 1.00 to 8.28, P=0.049) and nuclear grade (G3 to 4 vs. G1: HR=2.81, 95%CI: 1.01 to 7.82, P=0.048) were independent prognostic factors of localized renal cell carcinoma after partial nephrectomy. Conclusions: The long-term cancer-specific survival rates of patients with localized renal cancer after partial nephrectomy are satisfactory. The type of operation (open, laparoscopic, or robotic) has no significant effect on survival. However, patients with older age, higher nuclear grade, and higher T stage have a lower cancer-specific survival rate. Grasping surgical indications, attaching importance to preoperative evaluation, perioperative management, and postoperative follow-up, could benefit achieving satisfactory long-term survival.

Visual function and retinal morphological changes after single suprachoroidal delivery of fluocinolone acetonide (Iluvien®) implant in eyes with chronic diabetic macular edema

BackgroundTo assess the efficacy and safety of supra-choroidal (SC) Iluvien in the management of chronic diabetic macular edema (DME).MethodsA retrospective interventional non-comparative consecutive case series including patients with chronic DME who received an SC Iluvien implant. All patients had persistent central macular thickness (CMT) ≥ 300µ after previous treatment with anti-vascular endothelial growth factor (VEGF) agents or laser photocoagulation. The main outcome measures were improvement of best-corrected visual acuity (BCVA), reduction of CMT, and detection of ocular hypertension/glaucoma or cataract formation. Friedman’s two-way ANOVA was used to analyze BCVA, intraocular pressure (IOP), and DME across different time points. P-value = 0.05.ResultsThe study included 12 eyes of 12 patients. Six patients (50%) were males. The median age was 58 years (range 52–76 years). The median duration of DM was 13 years (range 8–20 years). Ten patients (83.3%) were phakic and 2 patients (17%) were pseudophakic. The median pre-operative BCVA was 0.07 (range 0.05–0.8). The median pre-operative CMT was 544µ (range 354–745µ). The median pre-operative IOP was 17 mmHg (range 14-21mmHg). The median follow-up period was 12 months, range (12–42). Post-operatively, the median final BCVA was 0.15 (range 0.03-1), p 0.02, the median CMT was 404µ (range 213–747), p 0.4 and the median IOP was 19.5 mmHg (range 15–22), p 1. Two out of 10 phakic patients (20%) developed nuclear sclerosis grade I by 12 months. Six patients (50%) developed a transient rise in IOP < 10 mmHg from the baseline that resolved within 3 weeks with antiglaucoma drops.ConclusionSC Iluvien is potentially effective in improving visual function, reducing macular edema, and reducing the incidence of steroid-induced cataracts and glaucoma.

Prognostic assessment of patients who receive radiotherapy for bone metastases from breast cancer.

For prognostic assessment in women who receive radiotherapy (RT) for bone metastases (BMs) from breast cancer (BC), prognostic factors specific for BMs from BC were investigated in the present study. The prognostic assessment was performed by retrospectively reviewing 143 women who received first-time RT for BMs from BC between January 2007 and June 2018. The median follow-up time and median overall survival (OS) time from the first-time RT for BMs were 22 and 18 months, respectively. In the multivariate analysis, nuclear grade 3 (NG 3) [hazard ratio, 2.18; 95% confidence interval (CI), 1.34-3.53], brain metastases (hazard ratio, 1.96; 95% CI, 1.01-3.81), liver metastases (hazard ratio, 1.75; 95% CI, 1.17-2.63), performance status (PS) (hazard ratio, 1.63; 95% CI, 1.10-2.41) and previous systemic therapy (hazard ratio, 1.58; 95% CI, 1.03-2.42) were significant factors for OS, whereas age, hormone-receptor/human epidermal growth factor receptor 2 status, number of BMs and synchronous lung metastases were not significant factors. When points according to risk levels [unfavorable points (UFPs)] were assigned to each risk factor (1.5 points for NG 3 and brain metastases; and 1 point for PS ≥2, previous systemic therapy and liver metastases), the median OS times of patients with a total number of UFPs ≤1 (n=45), 1.5-3 (n=55) and ≥3.5 (n=43) were 36, 17 and 6 months, respectively. Overall, in patients who received first-time RT for BMs from BC, NG 3, brain/liver metastases, poor PS and previous systemic therapy were unfavorable prognostic factors. Comprehensive prognostic assessment using these factors seemed to be useful for the prediction of prognoses in patients with BMs from BC.

Application of ion implantation as a tool to study neutron induced morphological changes in HOPG and RBMK-1500 reactor graphite

Based on the RBMK-1500 (rus.: peaктop бoльшoй мoщнocти кaнaльный, PБMК; reaktor bolshoy moshchnosti kanalnyy, “high-power channel-type reactor”) reactor irradiation conditions, ion implantation was used as a tool to study neutron induced morphological changes in both highly oriented pyrolytic graphite (HOPG) and nuclear grade RBMK graphite. Graphite samples were implanted with 180 keV 14N+ ions at the fluences of 1.0 × 1016 ions/cm−2 and 2.5 × 1016 ions/cm−2. To study temperature effects on both ion migration and structural disorder level in the graphite matrix, the implantation procedures were carried out under different temperature conditions – room temperature (RT) and 500 °C. Subsequently, the distribution profiles of the implanted 14N+ ions were obtained by using secondary ion mass spectroscopy (SIMS) technique, while the microstructural properties of the graphite were evaluated by Raman spectroscopy. Implantation induced primary displacement damage profiles and implanted ion profiles were evaluated theoretically by using GEANT4 10.6 and SRIM-2013 codes. The profiles of implanted nitrogen obtained by SIMS technique were found to be in good agreement with theoretical ones. The surfaces of HOPG samples displayed macroscopic damage in form of fractures after 14N+ ion implantation at 500 °C; however, in case of RBMK graphite, the sample surfaces remained without visually observable changes. The Raman spectra showed an increase of sp3-related content and formation of amorphous carbon in both HOPG and RBMK graphite samples; the latter exhibits higher structural disorder at microscopic level and stronger amorphization than HOPG.

Improved design of metal fiber filter materials: Experiment and theory

After a fire accident in a spent fuel reprocessing site of a nuclear power plant, the radioactive aerosol produced by the combustion is one of the main objects of accident control. Because metal fiber has good high temperature and radiation resistance, it is the preferred material for nuclear-grade filters. Taking nuclear grade filter's requirements as the evaluation index, this paper optimizes the design of metal fiber structure parameters. Under the currently limited technology, the best structural parameters are obtained by changing the fiber's basic weight and thickness of the filter layer. In addition, a protective layer and a structural layer are added on both sides to avoid damage to the filter layer during pleating and experimentation. The results show that the resistance caused by the protective layer is small, but it can improve the fiber efficiency to a certain extent, while the structural layer has little effect on the fiber performance. The optimal fiber structure parameters to meet the requirements of nuclear-grade filters are: the thickness of the fiber filter layer is 0.5 mm, and the basic weight is 950 g/m2. This work can provide a reference for the application of metal fibers to nuclear grade filters.

Cytology of micropapillary mucinous carcinoma: A case report of a clinically and genetically distinct breast carcinoma variant.

Micropapillary mucinous carcinoma (MPMC) is an uncommon histopathological variant of breast cancer accounting for approximately one-fifth of all mucinous breast carcinomas. In contrast to pure mucinous carcinoma, MPMC tends to affect younger women and is associated with decreased progression-free survival, higher nuclear grade, lymphovascular invasion, lymph node metastasis, and positive HER2 status. Typically MPMC histology shows micropapillary architecture with "hobnailing" of cells and reverse polarity. Very few publications document the cytomorphological findings of MPMC. We report a case of MPMC that was suspected in fine needle aspiration cytology (FNAC) and confirmed at histopathology.

High temperature annealing of irradiated nuclear grade graphite

Previous work has shown that the material properties of nuclear grade graphite are substantially affected by the atomic and microstructural changes that occur during neutron-irradiation. The parameters that play a role in these changes are irradiation dose, temperature, graphite composition and the initial microstructure of the graphite. Understanding the details of how these material changes occur and exactly what the changes consists of will enable the prediction of the material property changes as a function of these variables. Other work has shown these atomic level and microstructural changes can be healed or annealed out by raising the irradiated graphite above its irradiation temperature. In this work, experiments were carried out to investigate how the properties of irradiated graphite recover when heated. By showing property recovery as a function of annealing temperature or energy, insight is provided into the type of damage that occurred during neutron-irradiation. The data presented here shows recovery of thermal diffusivity, coefficient of thermal expansion, Young's modulus and electrical resistivity between annealing temperatures of 500 °C and 2380 °C. Graphite grades NBG-18, IG-110 and PCEA are considered that were both stressed and unstressed during irradiation.

The significance of spread through air spaces in the prognostic assessment model of stage I lung adenocarcinoma and the exploration of its invasion mechanism.

Spread through air spaces (STAS) is a crucial invasive mode of lung cancer and has been shown to be associated with early recurrence and metastasis. We aimed to develop a prognostic risk assessment model for stage I lung adenocarcinoma based on STAS and other pathological features and to explore the potential relationship between CXCL-8, Smad2, Snail, and STAS. 312 patients who underwent surgery at Harbin Medical University Cancer Hospital with pathologically diagnosed stage I lung adenocarcinoma were reviewed in the study. STAS and other pathological features were identified by H&E staining, and a prognostic risk assessment model was established. The expression levels of CXCL8, Smad2, and Snail were determined by immunohistochemistry. The nomogram was established based on age, smoking history, STAS, tumor lymphocyte infiltration, tissue subtype, nuclear grade, and tumor size. The C-index for DFS was (training set 0.84 vs validation set 0.77) and for OS was (training set 0.83 vs validation set 0.78). Decision curve analysis showed that the model constructed has a better net benefit than traditional reporting. The prognostic risk score validated the risk stratification value for stage I lung adenocarcinoma. STAS was an important prognostic factor associated with stronger invasiveness and higher expression of CXCL8, Smad2, and Snail. CXCL8 was associated with poorer DFS and OS. We developed and validated a survival risk assessment model and the prognostic risk score formula for stage I lung adenocarcinoma. Additionally, we found that CXCL8 could be used as a potential biomarker for STAS and poor prognosis, and its mechanism may be related to EMT.

Clinical Characteristics and Prognosis of Metaplastic Breast Cancer Compared with Invasive Ductal Carcinoma: A Propensity-Matched Analysis.

Metaplastic breast cancer (MpBC) is an aggressive histologic type of breast cancer. Although MpBC has a poor prognosis and is responsible for a large proportion of breast cancer mortalities, the clinical features of MpBC compared with invasive ductal carcinoma (IDC) are not well known, and the optimal treatment has not been identified. We retrospectively reviewed medical records of 155 MpBC patients and 16,251 IDC cases who underwent breast cancer surgery in a single institution between January 1994 and December 2019. The two groups were matched 1:4 by age, tumor size, nodal status, hormonal receptor status, and HER2 status using propensity-score matching (PSM). Finally, 120 MpBC patients were matched with 478 IDC patients. Disease-free survival and overall survival of MpBC and IDC patients both before and after PSM were analyzed by Kaplan-Meier survival, and multivariable Cox regression analysis was performed to identify variables affecting long-term prognosis. The most common subtype of MpBC was triple-negative breast cancer, and nuclear and histologic grades were higher than those of IDC. Pathologic nodal staging of the metaplastic group was significantly lower than that of the ductal group, and more frequent adjuvant chemotherapy was performed in the metaplastic group. Multivariable Cox regression analysis indicated that MpBC was an independent prognostic factor for disease-free survival (HR = 2.240; 95% CI, 1.476-3.399, p = 0.0002) and overall survival (HR = 1.969; 95% CI, 1.147-3.382, p = 0.0140). However, survival analysis revealed no significant difference between MpBC and IDC patients in disease-free survival (HR = 1.465; 95% CI, 0.882-2.432, p = 0.1398) or overall survival (hazard ratio (HR) = 1.542; 95% confidential interval (CI), 0.875-2.718, p = 0.1340) after PSM. Although the MpBC histologic type had poor prognostic factors compared with IDC, it can be treated according to the same principles as aggressive IDC.

Abstract HER2-04: HER2-04 Prevalence of HER2-low among Metastatic Breast Cancer Patients and Their Outcomes Compared to HER2 IHC 0

Abstract Prevalence of HER2-low among Metastatic Breast Cancer Patients and Their Outcomes Compared to HER2 IHC 0 Background: Amplification and/or overexpression of the HER2 gene is detected in approximately 15% to 20% of breast cancer (BC) patients. HER2-targeted therapies improve survival in HER2+ BC. Current HER2 diagnostic tests and thresholds were designed and optimized to predict benefit from HER2-directed therapies. The DESTINY-Breast04 trial demonstrated notable efficacy of HER2 antibody-drug conjugate trastuzumab deruxtecan, in patients whose tumors are not conventionally HER2+, but defined as HER2-low (IHC 1 or 2+ without HER2 amplification). A better understanding of the HER2-low phenotype is therefore of critical importance. Methods: Eligible pts were adults with metastatic HER2 IHC (0,1+,2+/FISH negative) BC seen at MD Anderson between 2006 and 2019. Primary biopsy of the breast was used to test biomarkers. HER2 low was defined as IHC 1+ or 2+ and FISH-negative. HER2-negative was defined as HER2 IHC 0. Multi-covariate logistic regression models were used to evaluate effect of clinical factors on HER2 low status and pCR. Overall survival (OS) was defined as time from diagnosis date until death. Disease free survival (DFS) was defined as time from definitive surgery date until the first local/distant recurrence or death from any cause. Patients alive without events (death for OS, recurrence/death for DFS) were censored at last follow-up date. OS and DFS times were estimated by Kaplan-Meier method. Multivariate Cox proportional hazards regression models were applied to assess effect of covariates of interest on OS and DFS. Results: A total of 3053 early stage and 1203 de novo female BC patients were included in the analysis. The prevalence of HER2 low for early stage patients was 59.3% (1811/3053) and for de novo metastatic disease 59.3% (713/1203). In early stage patients, white race, higher nuclear grade and positive ER status were significantly associated with HER2 low status in multicovariate logistic regression. Univariately, pCR rate was significantly associated with negative ER (10.2% in negative vs 2.7% in positive), negative PR (8.6% vs 2%) and negative lymphatic vascular invasion (9.2% vs 2%). Multicovariate logistic regression showed ER (p=0.0124), PR (p=0.0439) status and lymphatic vascular invasion (p&amp;lt; 0.0001) were significantly associated with pCR status. With median follow-up of 8.5 years, median OS time was 5.3 years (95% CI: [4.9, 5.4]), 5.4 years and 4.8 years in HER2 low and HER2 0 groups, respectively. In multicovariate Cox regression, HER2 low was significantly associated with longer OS (HR=0.87, p=0.008), adjusted for age, race, stage, nuclear grade, lymphatic-vascular invasion and ER/PR status. In patients who received neoadjuvant chemotherapy, adjusted for stage, nuclear grade, ER and PR status and pCR, HER2 low was significantly associated with a longer OS time (HR=0.87, p=0.04). Median DFS time was 1.9 years (95% CI: (1.8, 2.0)). Age, stage, histology, nuclear grade, and ER and PR status were significantly associated with DFS by multicovariate Cox regression. Among de novo cases, higher nuclear grade (HR [II vs I]=1.838, p =0.008; HR [III vs I]=1.856, p=0.007) and positive ER status (OR=1.933, p &amp;lt;.0001) were associated with high percentage of HER2 low by multicovariate logistic regression. Median OS time was 3.2 years (95% CI: (3.0, 3.5)). By multicovariate Cox regression, race, histology, nuclear grade, ER and PR status, and HER2 low status (HR=0.834, p=0.0260) were significantly associated with OS time. Conclusions: In metastatic BC pts, HER2 low status was significantly associated with a longer OS and DFS when compared to HER2 0. Nuclear grade and ER positivity was significantly associated with HER2 low status. Biomarkers on recurrence tumor will be presented. This real world data helps to establish the prevalence of HER2 low and their outcomes for this selective cohort. Citation Format: Akshara Singareeka Raghavendra, Diane Liu, Jason Mouabbi, Debu Tripathy. HER2-04 Prevalence of HER2-low among Metastatic Breast Cancer Patients and Their Outcomes Compared to HER2 IHC 0 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr HER2-04.

Abstract PD15-07: PD15-07 7-gene predictive biosignature improves risk stratification for breast ductal carcinoma in situ patients compared to clinicopathologic criteria, identifying a low risk group not clinically benefiting from adjuvant radiotherapy

Abstract Background: Prognostic and predictive tools are needed to optimize treatment for women diagnosed with ductal carcinoma in situ (DCIS). While radiotherapy (RT) is standard of care for DCIS after breast conserving surgery (BCS), those at low-risk for ipsilateral breast recurrence (IBR) risk may be treated without RT. Low-risk has been defined as the absence of high risk clinicopathologic (CP) factors, including larger (&amp;gt;2 cm), palpable, or high nuclear grade (NG) tumors, and younger age (&amp;lt; 50 yrs). However, prospective trials have failed to identify low risk patients (pts) who do not clinically benefit from RT after BCS (RTOG 9804). DCISionRT® (PreludeDxTM, CA) is a 7-gene predictive biosignature providing a validated score (DS) to assess the 10-yr IBR risk and RT benefit, using individual tumor biology and CP factors. This study assessed total 10-yr IBR rates, RT benefit, and number needed to treat (NNT) for risk groups defined by biosignature and CP criteria. Methods: DCIS patients (n=926) from four international cohorts (median follow up 8.5 yrs, 1-3rd quartile 5.8 – 10.2 yrs) treated with BCS (negative margins), with (n=641) and without RT (n=335), had formalin-fixed paraffin-embedded tissues analyzed at a CLIA lab (PreludeDx, Laguna Hills, CA) for DCISionRT with a Residual Risk subtype (RRt). A biosignature Low Risk group (DS≤2.8 without RRt) was contrasted to a High Risk group comprising Elevated Risk (DS&amp;gt;2.8 without RRt) and Residual Risk (DS&amp;gt;2.8 with RRt) groups. Low-risk CP groups were RTOG 9804-like (NG1-2, non-palpable, negative margins, screening detected) or (age &amp;gt;50 and NG 1-2). Total 10-yr IBR rates were evaluated using Cox Proportional Hazards and Kaplan Meier analysis by treatment, biosignature and CP risk groups. NNT was determined with 10-yr IBR rate differences with RT. Results: The biosignature classified 37% (n=338) of women as Low Risk and 63% (n=588) as High Risk. Among women who did not receive RT, biosignature Low Risk pts had lower IBR than biosignature High Risk pts (5.6% vs. 25.7%, p&amp;lt;.001). About half of pts defined as CP low-risk by 9804-like (51%) or favorable Age/NG (58%) criteria were reclassified by the biosignature to High Risk. These pts had significant RT benefit: 9804-like group - HR 0.3, p=.007, absolute 10-yr IBR reduction of 12.7%, and for favorable Age/NG group - HR .34, p=0.012, absolute 10-yr IBR reduction of 11.2%. The corresponding NNTs were ~8-9. Overall, RT significantly reduced IBR for biosignature High Risk patients (p&amp;lt;.001, n=588), with an absolute 17.7% reduction and a NNT of ~6. For patients in CP high risk groups, 23% of not-9804-like and 31% of (age&amp;lt; 50 or NG 3) pts were reclassified as biosignature Low Risk. RT did not significantly reduce IBR in any Low Risk Biosignature group, including those in CP high-risk groups. IBR for not-9804-like group was 5.9% vs 3.0% without and with RT, p=.52, and for (age&amp;lt; 50 or NG 3) pts was 4.4% vs 3% without and with RT, p=.70. For CP low-risk and biosignature Low Risk groups, RT reduced IBR by 0%. Overall, RT did not significantly reduce IBR rate for biosignature Low Risk patients (p=.71, n=338), with a 0.8% absolute 10-yr IBR rate difference and a NNT of ~100. Conclusion: In a large multicenter population, DCISionRT was a better predictor of 10-yr prognosis and RT benefit than CP criteria alone. Pts with biosignature Low Risk disease, comprising about 1/3 of CP high-risk pts, had no significant RT benefit. Whereas pts with biosignature High Risk disease, comprising about 1/2 of CP low-risk pts, significantly benefited from RT, highlighting the lack of accuracy of these CP factors in assessing RT benefit. Table 1. Ten-Year Risk of Ipsilateral Breast Recurrence (IBR) Citation Format: Rachel Rabinovitch, Frank Vicini, Chirag Shah, Julie A. Margenthaler, Brian J. Czerniecki, Pat Whitworth, DAVID J. DABBS, G Bruce Mann, Fredrik Wärnberg, Sheila Weinmann, Michael Leo, Jess Savala, Steven C. Shivers, Karuna Mittal, Troy Bremer. PD15-07 7-gene predictive biosignature improves risk stratification for breast ductal carcinoma in situ patients compared to clinicopathologic criteria, identifying a low risk group not clinically benefiting from adjuvant radiotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-07.

Abstract P1-04-11: Tumor Infiltrating Lymphocytes in initial HER2-Low breast cancer

Abstract Rationale Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer (BC) represents a distinct subgroup of patients (pts) that derives significant benefits from anti-HER2 therapy. More recently, patients with metastatic BC that were previously considered HER2-Negative but with low positivity by immunohistochemistry (IHC) and a negative in situ hybridization (ISH) (HER2 1+, or 2+ with negative ISH) derived benefit from treatment with trastuzumab-deruxtecan (T-Dxd), an antibody-drug conjugate that targets HER2 receptor. This novel subgroup, termed HER2-Low (H-Low), represents nearly 60% of BCs. Tumor infiltrating-lymphocytes (TILs) are a biomarker that can be easily analyzed without additional stains, and that tend to be higher in tumors with more aggressive features. High levels of TILs can predict better outcomes in triple-negative (TN) and HER2-Positive (H-Pos) tumors. To date, there is no information about TILs levels in H-Low tumors. Objectives This work aims to determine TILs levels in HER2-Low tumors and their correlation with clinicopathologic features. Methods We retrospectively analyzed tissue from breast surgical products in a tertiary hospital in Sao Paulo, Brazil, from January 2021 to March 2022. Inclusion criteria were stage I to III invasive BC and available data for TILs, HER2, estrogen receptor (ER), progesterone receptor (PR) by IHC, and ISH, when applicable. Exclusion criteria was neoadjuvant therapy. We extracted clinical, histopathologic, and IHC parameters. HER2 subtypes were defined as follows: HER2-Negative (H-Neg) when HER2 0+ in IHC; H-Low when IHC 1+, or 2+ with ISH negative; and H-Pos when IHC 3+ or 2+ with ISH positive. TILs were defined as absent (0), low (1 to 9%), intermediate (10 to 39%) and high (&amp;gt;40%). Ki-67 levels were divided as low (up to 19%) and high (≥20%). Results We included 202 eligible pts. 128 were H-Neg, 51 were H-Low (35 IHC 1+ and 16 IHC 2+ with ISH negative), and 23 were H-Pos. Four pts were TN in H-Neg and none in H-Low group. The mean ages for H-Neg, H-Low and H-Pos were 57, 51, and 57 years, respectively. ER and PR were negative in 3.1% and 11.7% of H-Neg, 0 and 7.8% of H-Low, and 52.4% and 56.5% of H-Pos. Ki-67 levels were high in 27.3% of H-Neg, 31.4% of H-Low and 82.6% of H-Pos. Nodal stages and multifocality were similar. Ductal histology had 89 (69.5%), 45 (88.2%), and 21 (91.3%) cases for H-Neg, H-Low, and H-Pos. Lobular carcinoma was found in 30 (23,4%) in H-Neg, 4 (7.8%) in H-Low, and none in the H-Pos group. Nuclear grade (NG) 2 was seen in 64.8% of H-Neg and 62% of H-Low. Nuclear grade 3 seen was in 82.6% of H-Pos. Histologic grade 1 was present in H-Neg and H-Low, with 29.7% and 25.5%; grade 2 was seen in 56.3% and 56.9%, respectively. In H-Pos grade 3 was found in 47.8%. Angiolymphatic invasion and perineural invasion were present in 26.6%, 35.3%, and 17.4%; and 26.6%, 35.3%, and 13% of H-Neg, H-Low and H-Pos respectively. TILs in H-Neg, H-Low, and H-Pos were, respectively, absent in 16.4%, 17.6%, and 8.7%; low in 69.5%, 52.9% and 34.8%; intermediate in 11.7%, 25.5% and 47.8%; and high in 2.3%, 3.9% and 8.7%. We divided samples into TILs levels to look at the distribution of HER2 subtypes. Absent, low, intermediate, and high TILs had respectively 32, 124, 39, and 7 cases. There were more H-Neg in low TILs and H-Pos in high TILs, with, respectively, 65.6% and 6.3% of absent; 71.8% and 6.5% of low; 38.5% and 28.2% of intermediate; and 42.9% and 28.6% of high TILs. Conversely, H-Low showed stability among the groups, with 28.1%, 21.8%, 33.3%, and 28.6% in absent, low, intermediate, and high TILs, respectively. Complete data and statistical analysis will be presented at the meeting. Conclusion TILs in H-Low are similar to H-Neg. Both had lower TILs compared to H-Pos pts. In our study, only 25% were defined as H-Low, which demonstrates that a better comprehension about prevalence or pathology concordance between HER2 IHC 0 and 1+ is warranted. TILs may not play a role as a biomarker in H-Low tumors. Citation Format: Italo Fernandes, Eduarda Damasceno, Rafael Kaliks, Marcus Corpa, Gustavo Schvartsman. Tumor Infiltrating Lymphocytes in initial HER2-Low breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-04-11.

Screening for important risk factors for cancer-specific mortality in patients with localized clear cell renal carcinoma

To study the risk factors for cancer-specific mortality (CSM) among patients with localized clear cell renal carcinoma (LCCRC) in the Chinese population. The clinical data of 1,376 LCCRC patients were postoperatively collected to analyze the correlations between CSM and multiple factors using Cox regression analysis. Receiver operating characteristic curves were constructed as per the screened risk factors to identify factors with optimal criticality judgment values, which were then used as the scoring standard for the stratification evaluation of LCCRC prognosis. The CSM rate was 5.6% (77/1,376 cases) and the median follow-up duration was 78.1 (60-105) months. Cox analysis revealed that age, tumor diameter, and nuclear grade were associated with CSM. The optimal criticality judgment values for age and tumor diameter using receiver operating characteristic curve analysis were 53 years and 5.8 cm, respectively. LCCRC prognosis divided into low-risk (≤ 2 points), intermediate-risk (3-4 points), and high-risk (5 points) showed CSM rates of 3.8%, 13.8%, and 58.3%, respectively, among patients with more than 5 years of follow-up. Age, tumor diameter, and nuclear grade were important risk factors for CSM in LCCRC patients. The scoring criteria including these three risk factors may be an important supplement to the prognostic model of LCCRC in the Chinese population.