Background: As pathologic complete response (pCR) is correlated with higher rates of event free survival, accurately forecasting pCR advances our collective endeavors in precision oncology to discern and translate individual patient-specific data into risk stratification. We developed the TumorScope engine, a software platform that utilizes pretreatment diagnostic data to build a computational tumor model that simulates in vivo tumor characteristics and interactions, incorporating morphology, metabolism, vascularity, and nutrient and drug delivery. This non-invasive approach enables accurate forecasting of a patient’s response to physician-chosen neoadjuvant chemotherapy-based treatment (NAC). Here we validate the prognostic capacity of this technology at a single site cancer center. Methods: A blinded, prospective trial using retrospective data was conducted at UNC. The study cohort included patients aged 18 years or older diagnosed with any subtype of breast cancer who were treated with a NAC regimen and had a pre-treatment T1-weighted dynamic contrast enhanced (DCE) MRI available. Pre-treatment diagnostic and planned treatment data (demographics, drug regimen, receptor status (ER/PR/HER2), DCE MRI, and pathology) were input into the TumorScope engine to simulate predicted final tumor volumes (Vt) for each tumor and predict pCR or residual disease (RD); pCR predictions were compared to post-surgery pathologic assessments defined as ypT0/is/N0. Predicted pCR was set at pre-defined threshold of predicted Vt less than 0.01 cm^3, or at least a 99.9% Vt reduction. Results: One hundred and fifty subjects with 157 tumors were enrolled in the study. After excluding missing data (absent DCE-MRI), a total of 143 cases in 136 patients were included. The majority of patients self-identified as Caucasian (63%) or African American (23%). TumorScope had a pCR overall prediction accuracy of 92.3% (95% CI: 86.7 - 96.1%) with a sensitivity of 90.9 % (95% CI: 75.7 - 98.1 %) and specificity of 92.7% (95% CI: 86.2 – 96.8%). Based on our subgroup analysis, predictive accuracy remained reliable for HR+/HER2- (n=65; 95.4%), HR+/HER2+ (n=20; 85.0%), HR-/HER2+ (n=21; 85.7%) and TNBC (n=37; 94.6%) subtypes. Predictive performance remained stable across ethnic subtypes and tumor grade (see Table 1). Conclusion: The TumorScope noninvasive method that incorporates imaging, pathologic, demographic and planned treatment data appears to accurately predict an individual patient’s probability of pCR across clinical subtypes. Table 1. TumorScope prediction performance. Citation Format: Cherie Kuzmiak, Terry S. Hartman, Thad Benefield, Joseph Peterson, Anuja K. Antony, Tushar Pandey, John A. Cole Jr, Benjaminc C. Calhoun, Lisa Carey. Independent Validation of a Novel, Non-invasive Approach to Predict Pathologic Complete Response (pCR) in a Blinded, Prospectively-Run Single Center Trial [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 P1-04-08.

Abstract Background: Stromal Tumor Infiltrating Lymphocytes (sTIL) are an established prognostic feature in triple-negative breast cancer, yet manual assessment or visual estimation of sTILs with conventional light microscopy may be subject to inter-pathologist variability. Recently published guidelines by the International TIL Working Group help address inter-pathologist variability, yet there remains a need for more objective and quantitative computational sTIL scoring. Methods: Our study used 120 triple-negative breast cancer slides (one slide per patient). A deep-learning based image analysis workflow is used to perform segmentation and classification of tissue regions and cells on the digital whole slide image. We used 14 annotated slides to train and validate the deep learning model, and to obtain image segmentation and classification accuracy statistics. Non-training slides were used to evaluate the concordance of manual (m-sTIL) and computationally derived (c-sTIL) scores. To generate data to create the model we manually annotated tissue regions in FFPE H&E stained digital slides, including: tumor, stroma, and necrosis. Initial classification of cell nuclei was performed using a semi-automated image analysis method, and then manually corrected to generate ground truth for tumor, stroma (fibroblasts), and lymphocytes. All annotations were performed by a trained research fellow and reviewed by a board-certified pathologist. Corresponding region and nucleus-level annotations were combined to train and validate a fully-convolutional neural network that jointly classifies tissue regions and cell nuclei. Tissue region segmentation accuracy was assessed by the Dice coefficient to measure degree of overlap between predicted tissue regions and ground truth annotations. Cell classification accuracy was assessed using area under curve (AUC). Two board-certified pathologists independently generated an m-sTIL score for all slides according to clinical guidelines, and discrepancies between pathologists were resolved by consensus. c-sTIL scores were calculated as the percentage of classified stromal areas occupied by nuclei classified as lymphocytic infiltrates. Results: Tissue region segmentation was accurate for both stroma (0.77 Dice) and tumor (0.83 Dice) regions, and accurate overall (0.78 Dice). Cell classification was highly accurate for lymphocytes (0.89 AUC), tumor cells (0.90 AUC), stromal cells (0.78 AUC), and overall (0.89 AUC, micro average). Inter observer spearman correlation between the m-sTIL scores of our two pathologists was 0.66 (p < 0.001). By comparison, the correlation between c-sTIL and consensus m-sTIL was higher at 0.73 (p < 0.001). Dichotomizing at a threshold sTIL score of 10%, c-sTIL scoring identifies low-sTIL patients with an accuracy of 85%. High- and Low- sTIL score patient groups show clear separation on a Kaplan-Meier curve for both c-sTIL and m-sTIL scoring approaches. Conclusions: Our pipeline quantifies stromal TILs with high concordance with manual pathologist scores, and sheds light on the ability of computational approaches in standardizing diagnostic pathology workflows. Future work will investigate how other computationally driven histology biomarkers can predict outcomes and help prognosticate breast cancer patients. Citation Format: Amgad M, Sarkar A, Srinivas C, Redman R, Ratra S, Bechert CJ, Calhoun BC, Mrazeck K, Kurkure U, Cooper LA, Barnes M. Computational scoring of tumor infiltrating lymphocytes in triple-negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-07-01.

Abstract Background: While immunotherapy holds promise in the treatment of mTNBC, response rates (RR) in unselected patients (pts) are approximately 20%. Strategies to augment response to immunotherapy include depletion of regulatory T cells (Tregs). A single dose of cyclophosphamide (Cy) given prior to checkpoint inhibition achieved this goal in preclinical models of TNBC (Taylor et al., JCI, 2017). Thus, we designed a phase II study to evaluate this strategy in the clinical setting of mTNBC. Patients/Methods: In cycle 1 (C1), eligible pts with mTNBC received a single dose of Cy 300mg/m2 IV on day 1 (C1D1) followed by pembrolizumab 200mg IV on day 2 (C1D2), then every 3 weeks thereafter. The co-primary objectives were (1) progression free survival (PFS, null 1.9 mos vs. 2.9 mos, 80% power, alpha 0.05) and (2) reduction in Tregs in peripheral blood measured by flow cytometry. Secondary endpoints were response rate (RR), survival (OS), and RNA-based correlative endpoints. Results: 40 patients were evaluable for efficacy: mean age 54.5 yrs (33 – 82 yrs), 75% white, 22% black, 3% American Indian. All patients had received 1 prior line of chemotherapy in the metastatic setting; 29% received 5 or more prior lines. The most common grade 3 adverse events (AE's), all 5%, were neutropenia, anemia, elevated AST, and fatigue. Immune-related grade 3 AE's, all 3%, included colitis, dry mouth, pneumonitis. Overall RR was 21% (0 CR, 8 PR), 3 pts had stable disease. Median PFS was 1.8 months (mos) (95% CI 1.4–2.5) and OS was 6.3 mos (95% CI 2.8–8.4). There was a non-significant decrease in Tregs from C1D1 to C1D2 (-3.3%, p=0.19); but from C1D2 to C2D1, Tregs increased 21.7% (p=0.005). There was no association between changes in Tregs or number of prior lines of therapy with RR (p>0.09), while immune-related AE's were associated with response (p=0.02). Correlatives studies illustrate B cell immune gene signature expression and B cell receptor repertoire diversity were enriched in responders, while genes/pathways associated with neutrophils, anti-apoptosis, PI3K/AKT and down-regulation of MHC class 1 were associated with non-response. Conclusions: While pembroliuzumab plus Cy was well-tolerated among pts with mTNBC, efficacy was similar to historical control, likely due to minimal effect of Cy on Tregs. Correlative analyses illustrate that study of adaptive immune features, including B cell biology, is a promising strategy for understanding response to PD-1 inhibition in breast cancer. Further strategies to deplete Tregs in a more sustained manner are worthy of future exploration (NCT02768701). Citation Format: Anders CK, Moore D, Sambade M, Cuaboy L, Garrett A, Woodcock M, McKinnon K, Cowens K, Bortone D, Calhoun B, Carey L, Dees C, Jolly T, Muss H, Reeder-Hayes K, Kaltman R, Jankowitz R, Gudena V, Olajide O, Perou C, Vincent B, Serody J. LCCC 1525: A phase II study of a priming dose of cyclophosphamide prior to pembrolizumab to treat metastatic triple negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-09-05.

Cylindromas are benign epithelial neoplasms derived from cutaneous eccrine adnexal structures. These tumors are most commonly encountered on the head, neck, and scalp of older women. In rare instances, solitary cylindromas may arise at other body sites. In the current case, a cylindroma of the skin of the breast was diagnosed by complete excision. Immunohistochemical studies confirmed the tumor cells to be immunoreactive with cytokeratin AE1/3, cytokeratin 5/6, cytokeratin 7, p63, and SOX10. The neoplastic cells were also noted to be immunoreactive with markers typically expected to be positive in ductal epithelium of the breast including GATA3, mammaglobin, and E-cadherin. The case emphasizes the importance of correlating clinical setting, imaging studies, patient history, and careful microscopic evaluation in arriving at an accurate diagnosis. This case also illustrates the point that not all “breast” tumors that are confirmed to be positive for GATA3, mammaglobin, and E-cadherin are derived from mammary ducts.

Abstract Columnar cell lesions of the breast are common findings in core biopsies for mammographically indeterminate calcifications. Atypical columnar cell lesions, also referred to as flat epithelial atypia (FEA), confer a mildly increased risk of subsequent carcinoma and are often co-localized with other patterns of atypia. The management of FEA diagnosed on core biopsy remains controversial with studies reporting carcinoma on excisional biopsy in 13 to 67% of cases. We report the frequency of carcinoma in excision specimens after a diagnosis of FEA on core biopsy over a nine year period at Carolinas Medical Center. Cases were identified from our files for the period from January 2004 through October 2012. Core biopsies with FEA as the most “advanced” lesion were included. Exclusion criteria included another pattern of atypia, carcinoma in situ, or invasive carcinoma in ipsilateral core biopsies performed concurrently or within four months of the core biopsy with FEA alone. The pathology reports for excision specimens following a core biopsy with FEA alone were retrieved. For each core biopsy with pure FEA, the histologic and mammographic findings were correlated. A total of 116 cases with a diagnosis of FEA on core biopsy were identified. Two (2) cases were ultrasound core biopsies, 1 was MRI-guided, and the remaining 113 cases were stereotactic core biopsies performed for calcifications. FEA was the most advanced lesion in 53 cases (46%), corresponding to 55 core biopsies. In the 63 cases with FEA and a more advanced lesion, 34 (29%) contained atypical ductal hyperplasia, 6 (5%) atypical lobular hyperplasia, 4 (3%) atypical ductal and lobular hyperplasia, 11 (10%) ductal carcinoma in situ, 2 (2%) lobular carcinoma in situ, and 6 (5%) invasive carcinoma. Of the 55 core biopsies with FEA alone, excision pathology reports were unavailable for 11 cases, and an ipsilateral core biopsy contained a more advanced lesion in 6 cases. Of the 38 remaining cases, 4 excision specimens (11%) contained carcinoma and 8 specimens (21%) contained another, higher risk pattern of atypia (atypical ductal hyperplasia or atypical lobular hyperplasia). Excision results are summarized in the table below: 10 (26%) contained no residual atypia, 16 (42%) residual FEA, 7 (18%) atypical ductal hyperplasia, 1 (3%) atypical lobular hyperplasia, 3 (8%) ductal carcinoma in situ, and 1 (3%) invasive carcinoma. Excision Findings after Pure FEA on Core BiopsyTotalNo AtypiaFEAADHALHDCISInvasive3810 (26%)16 (42%)7 (18%)1 (3%)3 (8%)1 (3%) The data from a nine year period at our institution demonstrate an 11% upgrade rate to carcinoma for patients with a diagnosis of FEA on core biopsy. The higher risk patterns of atypia (atypical ductal hyperplasia or atypical lobular hyperplasia) found in 21% of cases also impact risk stratification and future clinical and radiographic follow-up. In total, future clinical management was altered in 32% of patients based on excision specimen results. The findings support performing an excisional biopsy for a core biopsy containing FEA. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-02-11.

The aim of the study was a prospective assessment of the possible consequences of a diagnosis of lipodystrophy on health-related quality of life (HRQL) and depressive symptomatology in HIV-seropositive men who have sex with men. A standardized physical assessment for lipodystrophy was introduced within a prospective study in April 1999. Over a 2-year follow- up, 37 HIV-seropositive men who met the criteria for lipodystrophy were longitudinally compared to 92 HIV-seropositive men without lipodystrophy and 88 HIV-seronegative men on measures of HRQL and depression. A series of questionnaires, which included the Medical Outcomes Study Short-Form 36 (SF-36) and the Center for Epidemiological Studies-Depression (CES-D), were administered to assess HRQL and depression, respectively. SF-36 scores were summarized using the mental and physical components; CES-D results were reported as both dichotomous (with or with clinical depression) and continuous scores. Neither the mental nor physical components of the SF-36 showed any significant differences between patients with lipodystrophy versus HIV-seropositive patients without lipodystrophy. Similarly, lipodystrophy status was not significantly associated with either continuous depression scores or presence of clinical depression. However, consistent with previous results, HIV-seropositive men without lipodystrophy (compared to HIV-seronegative men) reported higher scores on both components of the SF-36 scales and both categorizations of the CES-D. The results of this study suggest that lipodystrophy does not negatively affect HRQL or depression, above and beyond, the diagnosis of HIV infection, although the impact of the severity of lipodystrophy on these conditions will require further study.

You have accessJournal of UrologyDiscussed Poster, Saturday, May 8, 2004, 1:00 - 5:00 pm1 Apr 2004150: Economic Impact of Urolithiasis Margaret S. Pearle, Gary C. Curhan, and Beth Calhoun Margaret S. PearleMargaret S. Pearle More articles by this author , Gary C. CurhanGary C. Curhan More articles by this author , and Beth CalhounBeth Calhoun More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)37412-3AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "150: Economic Impact of Urolithiasis." The Journal of Urology, 171(4S), p. 40 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 171Issue 4SApril 2004Page: 40 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Margaret S. Pearle More articles by this author Gary C. Curhan More articles by this author Beth Calhoun More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyDiscussed Poster, Monday, May 10, 2004, 8:00 am - 12:00 pm1 Apr 2004878: Relationship Between Objective and Subjective Assessments of Erectile Dysfunction Beth Calhoun, Emily Welshman, John Cashy, David Cella, and Kevin T. McVary Beth CalhounBeth Calhoun More articles by this author , Emily WelshmanEmily Welshman More articles by this author , John CashyJohn Cashy More articles by this author , David CellaDavid Cella More articles by this author , and Kevin T. McVaryKevin T. McVary More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)38127-8AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "878: Relationship Between Objective and Subjective Assessments of Erectile Dysfunction." The Journal of Urology, 171(4S), pp. 232–233 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 171Issue 4SApril 2004Page: 232-233 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Beth Calhoun More articles by this author Emily Welshman More articles by this author John Cashy More articles by this author David Cella More articles by this author Kevin T. McVary More articles by this author Expand All Advertisement Loading ...

You have accessJournal of UrologyDiscussed Poster, Saturday, May 8, 2004, 1:00 - 5:00 pm1 Apr 2004140: Urinary Incontinence in Men: National Trends in Health Care Resource Utilization and Economic Impact Lynn Stothers, David H. Thorn, Beth Calhoun, and Urologic Diseases in America Project Lynn StothersLynn Stothers More articles by this author , David H. ThornDavid H. Thorn More articles by this author , Beth CalhounBeth Calhoun More articles by this author , and Urologic Diseases in America Project More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)37402-0AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "140: Urinary Incontinence in Men: National Trends in Health Care Resource Utilization and Economic Impact." The Journal of Urology, 171(4S), p. 37 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 171Issue 4SApril 2004Page: 37 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Lynn Stothers More articles by this author David H. Thorn More articles by this author Beth Calhoun More articles by this author Urologic Diseases in America Project More articles by this author Expand All Advertisement PDF downloadLoading ...

OBJECTIVE:Advances in laparoscopic surgical techniques and ultrasound technology along with the popularization of treatment with methotrexate have revolutionized accepted algorithms for treating ectopic pregnancy. I analyzed the management of ectopic pregnancy at a military medical center.METHODS:A retrospective chart review of ectopic pregnancies at Womack Army Medical Center between January 1997 and July 1999 was conducted.RESULTS:A total of 129 cases of ectopic pregnancy were found. Of those, 77 patients received primary surgical management, 51 patients received primary therapy with methotrexate, and 1 patient was managed expectantly. Eleven patients failed methotrexate therapy and went on to surgical therapy. Of the 88 patients ultimately treated surgically, 76 underwent laparoscopic procedures, 12 received laparotomy, and 11 more converted from laparoscopy to laparotomy.CONCLUSION:The advent of methotrexate therapy has greatly facilitated the treatment of ectopic pregnancy and altered our institutional algorithm; however, primary surgery is still used more often.

To determine whether men are able to self-diagnose external genital warts (EGWs), we studied data from 1115 men with and without human immunodeficiency virus infection. Men were largely unable to accurately assess the presence of EGWs. Self-reporting of EGWs was not a sensitive tool; only 38% of men who had EGWs diagnosed by a trained examiner who used bright light and visual inspection also reported having them. When we controlled for other covariates in a multivariate model, men who had EGWs diagnosed by an examiner were 14 times less likely to show concordance between examiner findings and self-report than were men who did not have EGWs diagnosed by an examiner (odds ratio, 0.07; 95% confidence interval, 0.06-0.09). Self-diagnosis and self-assessment may not accurately reflect the presence of EGWs, and self-diagnosis should not be used in place of an examiner's findings for epidemiologic studies that seek to determine the cause of disease.