Review of Radiologic and Pathologic Features of Carcinomas and High Risk Lesions Arising from Fibroadenomata: Need for Continued Surveillance for Fibroadenomata and Lessons Learnt from our own Experience

2013 ◽  
Vol 02 (01) ◽  
Author(s):  
Chia Mei Yee Elizabeth ◽  
Mark Tan Ming Long ◽  
Mancer Kent
Keyword(s):  
High Risk ◽  
Lessons Learnt ◽  
Pathologic Features

scholarly journals Outcomes of Post-Operative Treatment with Concurrent Chemoradiotherapy (CRT) in High-Risk Resected Oral Cavity Squamous Cell Carcinoma (OCSCC): A Multi-Institutional Collaboration

2021 ◽  
Vol 28 (4) ◽  
pp. 2409-2419
Author(s):  
Arslan Babar ◽  
Neil M. Woody ◽  
Ahmed I. Ghanem ◽  
Jillian Tsai ◽  
Neal E. Dunlap ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Demographic Data ◽  
Disease Free Survival ◽  
Total Sample ◽  
High Dose ◽  
Pathologic Features

Adjuvant chemoradiation (CRT), with high-dose cisplatin remains standard treatment for oral cavity squamous cell carcinoma (OCSCC) with high-risk pathologic features. We evaluated outcomes associated with different cisplatin dosing and schedules, concurrent with radiation (RT), and the effect of cumulative dosing of cisplatin. An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I–IVB AJCC 7th edition) treated with primary surgical resection between January 2005 and January 2015, with or without adjuvant therapy, was established from six academic institutions. Patients were categorized by cisplatin dose and schedule, and resultant groups compared for demographic data, pathologic features, and outcomes by statistical analysis to determine disease free survival (DFS) and freedom from metastatic disease (DM). From a total sample size of 1282 pts, 196 pts were identified with high-risk features who were treated with adjuvant CRT. Administration schedule of cisplatin was not significantly associated with DFS. On multivariate (MVA), DFS was significantly better in patients without perineural invasion (PNI) and in those receiving ≥200 mg/m2 cisplatin dose (p < 0.001 and 0.007). Median DFS, by cisplatin dose, was 10.5 (<200 mg/m2) vs. 20.8 months (≥200 mg/m2). Our analysis demonstrated cumulative cisplatin dose ≥200 mg/m2 was associated with improved DFS in high-risk resected OCSCC pts.

303 Phase II trial of neoadjuvant nivolumab (Nivo) and intra-tumoral (IT) CMP-001 in high-risk resectable melanoma (Neo-C-Nivo): final results

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A330-A330
Author(s):  
Diwakar Davar ◽  
Arivarasan Karunamurthy ◽  
Douglas Hartman ◽  
Richelle DeBlasio ◽  
Joe-Marc Chauvin ◽  
...  
Keyword(s):  
T Cells ◽  
High Risk ◽  
Cd8 T Cells ◽  
Advanced Melanoma ◽  
Pathologic Response ◽  
Type I ◽  
List Type ◽  
Cell Lung Carcinoma ◽  
Radiographic Response ◽  
Pathologic Features

BackgroundNeoadjuvant PD-1 blockade produces major pathological responses (MPR) in ~30% of patients (pts) with high-risk resectable melanoma (MEL) with durable relapse-free benefit, and increased circulating activated CD8+ T cells.1 2 CMP-001 is a type A CpG packaged within a virus-like particle that activates tumor-associated plasmacytoid dendritic cells (pDC) via TLR9 inducing type I interferons and anti-tumor CD8+ T cells. CMP-001/pembrolizumab produces durable anti-tumor responses in PD-1 refractory melanoma.3 We previously reported preliminary evidence of efficacy of neoadjuvant IT CMP/Nivo in high-risk resectable MEL; and herein present final results on 30 evaluable patients.Methods30 pts with stage III B/C/D MEL were enrolled. Pre-operatively, CMP-001 was dosed at 5 mg subcutaneous (SC, 1st), then 10 mg IT (2nd-7th) weekly; Nivo was dosed 240 mg q2 weeks for 3 doses – both agents given for 7 weeks. Post-operatively, Nivo was dosed 480 mg q4 weeks with CMP-001 5 mg q4 weeks SC for 48 weeks. Primary endpoints included major pathologic response rate (MPR), and incidence of dose-limiting toxicities (DLT). Secondary endpoints were radiographic response, relapse-free survival (RFS) and overall survival (OS). Pathological response was scored blinded by pathologists based on residual volume of tumor (RVT) using prior specified cutoffs:4 60% (complete response, pCR); 0%<rvt<rvt50% (non-response, pNR). Radiographic response was assessed using RECIST v1.1. Sequential blood draws and tumor biopsies were collected and analyzed for CD8+ T cell infiltrate (TIL), multiparameter flow cytometry (MFC) and multiplex immunofluorescence (mIF).Results30 pts with regionally advanced MEL were enrolled, of stages IIIB (57%), IIIC (37%), IIID (7%). 29/30 (97%) of pts completed 7 weeks of neoadjuvant Nivo/CMP; while 1 pt had a delay in surgery related to a pre-operative infection unrelated to therapy. No DLTs were reported; grade 3/4 irAE were reported in 3 pts (11%) leading to CMP-001 discontinuation in 2 pts (7%). Radiographic responses were seen in 13 pts (43%), while 9 pts (30%) had stable disease and 8 pts (27%) had progressive disease. Pathological responses (RVT <50%) were seen in 70% of pts: pCR 15 (50%), pMR 3 (10%), 3 pPR (10%); only 9 (30%) had pNR. Pathological responders (pCR/pMR) had increased CD8+ TIL and CD303+ pDC intra-tumorally by mIF; and peripherally activated PD1+/Ki67+ CD8+ T cells by MFC.ConclusionsNeoadjuvant CMP/Nivo has acceptable toxicity and promising efficacy. MPR is 60% in 30 pts. 1-year RFS was 82% (all pts) and 89% (among those with pCR/pMR); median RFS is 9 months (among pNR/pPR) and not reached (among pCR/pMR). Response is associated with evidence of immune activation intra-tumorally and peripherally. IT CMP001 increases clinical efficacy of PD-1 blockade with minimal additional toxicity in pts with regionally advanced MEL. Further study of this combination in high-risk resectable MEL is planned.AcknowledgementsWe thank Dr. Jagjit Singh and the pathology grossing room staff for their assistance and Checkmate Pharmaceuticals for funding and CMP-001.Trial RegistrationClinical trial information: NCT03618641Ethics ApprovalThe study was approved by University of Pittsburgh’s Institutional Review Board, approval number MOD19040237-002.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.ReferencesAmaria RN, Reddy SM, Tawbi HA, et al. Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma. Nat Med 2018. Nov;24(11):1649–1654.Huang AC, Orlowski RJ, Xu X, et al. A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma. Nat Med 2019. Mar;25(3):454–461. doi: 10.1038/s41591-019-0357-y.Milhem M, Gonzales R, Medina T, et al. Abstract CT144: Intratumoral toll-like receptor 9 (TLR9) agonist, CMP-001, in combination with pembrolizumab can reverse resistance to PD-1 inhibition in a phase Ib trial in subjects with advanced melanoma. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14–18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract CT144.Tetzlaff MT, Messina JL, Stein JE, et al. Pathological assessment of resection specimens after neoadjuvant therapy for metastatic melanoma. Ann Oncol 2018. Aug 1;29(8):1861–1868.Cottrell TR, Thompson ED, Forde PM, et al. Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC). Ann Oncol 2018 Aug 1;29(8):1853–1860. doi: 10.1093/annonc/mdy218.Stein JE, Soni A, Danilova L, et al. Major pathologic response on biopsy (MPRbx) in patients with advanced melanoma treated with anti-PD-1: evidence for an early, on-therapy biomarker of response. Ann Oncol 2019 Apr 1;30(4):589–596. doi: 10.1093/annonc/mdz019.

scholarly journals Observation with or without late radiotherapy is equivalent to early radiotherapy in high-risk prostate cancer after radical prostatectomy: A SEER-Medicare analysis on trends, survival outcomes and complications

2019 ◽  
Author(s):  
Young Suk Suk Kwon ◽  
Wei Wang ◽  
Arnav Srivast ◽  
Thomas L Jang ◽  
Singer A Eric ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Cox Regression ◽  
Survival Outcomes ◽  
Study Cohort ◽  
High Risk Prostate Cancer ◽  
Pathologic Features ◽  
Risk Prostate Cancer

Abstract Introduction: While early radiotherapy (eRT) after radical prostatectomy (RP) has shown to improve oncologic outcomes in patients with high-risk prostate cancer (PCa) in a recent clinical trial, controversy remains regarding its benefit. We aimed to illustrate national trends of post-RP radiotherapy and compare outcomes and toxicities in patients receiving eRT vs. observation with or without late radiotherapy (lRT). Methods: Utilizing the Surveillance, Epidemiology and End Results (SEER)-Medicare data from 2001 to 2011, we identified 7557 patients with high-risk pathologic features after RP (≥ pT3N0 and/or positive surgical margins). Our study cohort was consisted of patients receiving RT within 6 months of surgery (eRT), those receiving RT after 6 months (IRT), and those never receiving RT (observation). Another subcohort, delayed RT (dRT), encompassed both IRT and observation. Trends of post-RP radiotherapy were compared using the Cochran-Armitage trend test. Cox regression models identified factors predictive of worse survival outcomes. Kaplan-Meier analyses compared the eRT and the dRT groups. Results: Among those with pathologically confirmed high-risk PCa after RP, 12.7% (n=959), 13.2% (n=1710), and 74.1% (n=4888) underwent eRT, lRT, and observation without RT, respectively. Of these strategies, the proportion of men on observation without RT increased significantly over time (p=0.004). Multivariable Cox regression model demonstrated similar outcomes between the eRT and the dRT groups. At a median follow up of 5.9 years, five-year overall and cancer-specific survival outcomes were more favorable in the dRT group, when compared to the eRT group. Radiation related toxicities, including urinary incontinence, erectile dysfunction, and urethral stricture, were higher in the eRT group when compared to the lRT group. Conclusions: Our results suggest that a blanket adoption of the eRT in high-risk PCa based on clinical trials with limited follow up may result in overtreatment of a significant number of men and expose them to unnecessary radiation toxicity.

The predictive value of magnetic resonance imaging of retinoblastoma for the likelihood of high-risk pathologic features

2018 ◽  
Vol 29 (2) ◽  
pp. 262-268 ◽  
Author(s):  
Jamila G Hiasat ◽  
Alaa Saleh ◽  
Maysa Al-Hussaini ◽  
Ibrahim Al Nawaiseh ◽  
Mustafa Mehyar ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Optic Nerve ◽  
High Risk ◽  
Magnetic Resonance ◽  
Predictive Value ◽  
Resonance Imaging ◽  
Cut Edge ◽  
Pathologic Features ◽  
Nerve Invasion ◽  
Choroidal Invasion

Purpose: To evaluate the predictive value of magnetic resonance imaging in retinoblastoma for the likelihood of high-risk pathologic features. Methods: A retrospective study of 64 eyes enucleated from 60 retinoblastoma patients. Contrast-enhanced magnetic resonance imaging was performed before enucleation. Main outcome measures included demographics, laterality, accuracy, sensitivity, and specificity of magnetic resonance imaging in detecting high-risk pathologic features. Results: Optic nerve invasion and choroidal invasion were seen microscopically in 34 (53%) and 28 (44%) eyes, respectively, while they were detected in magnetic resonance imaging in 22 (34%) and 15 (23%) eyes, respectively. The accuracy of magnetic resonance imaging in detecting prelaminar invasion was 77% (sensitivity 89%, specificity 98%), 56% for laminar invasion (sensitivity 27%, specificity 94%), 84% for postlaminar invasion (sensitivity 42%, specificity 98%), and 100% for optic cut edge invasion (sensitivity100%, specificity 100%). The accuracy of magnetic resonance imaging in detecting focal choroidal invasion was 48% (sensitivity 33%, specificity 97%), and 84% for massive choroidal invasion (sensitivity 53%, specificity 98%), and the accuracy in detecting extrascleral extension was 96% (sensitivity 67%, specificity 98%). Conclusions and relevance: Magnetic resonance imaging should not be the only method to stratify patients at high risk from those who are not, eventhough it can predict with high accuracy extensive postlaminar optic nerve invasion, massive choroidal invasion, and extrascleral tumor extension.

PREDICTIVE VALUE OF TNM CLASSIFICATION, INTERNATIONAL CLASSIFICATION, AND REESE–ELLSWORTH STAGING OF RETINOBLASTOMA FOR THE LIKELIHOOD OF HIGH-RISK PATHOLOGIC FEATURES

Retina ◽  
2015 ◽  
Vol 35 (9) ◽  
pp. 1883-1889 ◽  
Author(s):  
Yacoub A. Yousef ◽  
Maysa Al-Hussaini ◽  
Mustafa Mehyar ◽  
Iyad Sultan ◽  
Imad Jaradat ◽  
...  
Keyword(s):  
High Risk ◽  
Predictive Value ◽  
Tnm Classification ◽  
International Classification ◽  
Pathologic Features

Optimal timing of post-prostatectomy radiotherapy for prostate cancer with high-risk pathologic features: A multi-institutional analysis.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 24-24
Author(s):  
William L. Hwang ◽  
Rahul D. Tendulkar ◽  
Andrzej Niemierko ◽  
Shree Agrawal ◽  
Kevin L. Stephans ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Locally Advanced ◽  
Distant Metastases ◽  
Recurrence Risk ◽  
Optimal Timing ◽  
Cancer Specific Survival ◽  
Prognostic Features ◽  
Kaplan Meier ◽  
Pathologic Features

24 Background: The use of radical prostatectomy (RP) as initial treatment of high-risk/locally-advanced prostate cancer is increasing but patients (pts) with adverse pathologic features such as positive surgical margins or T3 disease have up to 70% recurrence risk. These high-risk pts may be managed with adjuvant radiotherapy (ART) or early salvage radiotherapy (ESRT). The optimal timing of post-operative radiotherapy is unclear. Methods: Individual data from 1566 consecutive pts with pT2N0M0/R1 or pT3N0M0/R0-1 disease who underwent post-prostatectomy ART or ESRT (1987-2013) at 10 academic centers were pooled. Post-irradiation freedom from biochemical failure (FFBF), freedom from distant metastases (FFDM), prostate-cancer specific survival (PCSS), and overall survival (OS) were compared using Kaplan-Meier and multivariate competing-risks regression (MVA) analyses. Propensity score (PS) matching was used to account for covariates potentially associated with treatment allocation. All outcomes were measured from the date of surgery to address lead time bias. Results: After PS-matching, median follow-up after surgery was 66 vs. 73 months for the ART and ESRT groups, respectively, and baseline characteristics were well-matched. ART was associated with higher FFBF (12-yr: 69% vs. 43%; log-rank P < 0.0001), FFDM (12-yr: 95% vs. 85%; log-rank P = 0.03), PCSS (12-yr: 99% vs. 94%; log-rank P = 0.048), and OS (12-yr: 91% vs. 79%; log-rank P = 0.01). ART, lower Gleason score, lower T-stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on MVA for BF. Sensitivity analysis demonstrated that the decreased risk of BF associated with ART remained significant unless more than 56% of ART pts were cured by surgery alone. This threshold is greater than the estimated 12-yr FFBF of 46% after RP alone as determined by a contemporary nomogram. Conclusions: To the best of our knowledge, this represents the largest multi-institutional study to date comparing ART to ESRT. ART was associated with reduced biochemical recurrence, distant metastases, and death compared to ESRT for high-risk pts, pending prospective validation.

Utility of the Breast Cancer Index (BCI) in the clinical practice.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14723-e14723
Author(s):  
Saranya Kodali ◽  
Eswar Tipirneni ◽  
Kim Dittus
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
High Risk ◽  
Endocrine Therapy ◽  
Early Stage ◽  
Late Recurrence ◽  
Low Risk ◽  
Breast Cancer Index ◽  
Pathologic Features ◽  
Poor Tolerance

e14723 Background: Extended endocrine therapy (EET) greater than 5 years in early stage hormone receptor positive (HR+) breast cancer (BC) patients has shown benefit. However, EET is associated with side effects and there is no validated assay to determine which group of patients would derive benefit. Breast Cancer Index (BCI) is a validated bio-marker test that incorporates 2 distinct genomic assays and is prognostic/predictive. The objective of this study is to assess patient characteristics, pathologic features and patient preferences with regards to extending endocrine therapy after reviewing the BCI results. Methods: We performed a retrospective chart review on early stage HR+ BC patients from Jan, 2016 to Jan, 2017 at the University of Vermont Medical Center. We identified 25 cases on whom BCI was submitted. Results: Median age was 68 years. Majority of the patients were stage IA (64%). 56% of the tumors were moderately differentiated. All patients were ER +ve and 12% were HER2+. Median tumor size was 1.4 cm (0.3-4). 76% had poor tolerance to the ET and preferred the test to be sent. In LN-patients, BCI identified 42% as high risk and 52% as low risk for late recurrence and 32% who derive high benefit from EET. In LN+ patients, BCI identified 75% as high risk for late recurrence and 25% as low risk for late recurrence. 40% of the entire group were identified to highly benefit from EET (70% agreed to continue ET and 30% denied due to side effects). Conclusions: BCI is a reasonable test to consider in early stage HR+ BC, especially in patients with poor tolerance to ET. This test might aid in decision making with tolerability/compliance challenges to EET. [Table: see text]

scholarly journals Role of prostate health index to predict Gleason score upgrading and high-risk prostate cancer in radical prostatectomy specimens

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hwanik Kim ◽  
Gyoohwan Jung ◽  
Jin Hyuck Kim ◽  
Seok-Soo Byun ◽  
Sung Kyu Hong
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Gleason Score ◽  
Primary Study ◽  
Health Index ◽  
Pathologic Features ◽  
Prostate Health Index ◽  
Prostate Health

AbstractWe evaluated the role of prostate health index (PHI) in predicting Gleason score (GS) upgrading in International Society of Urological Pathology Grade Group (ISUP GG) 1 & 2 prostate cancer (PCa) or adverse pathologic outcomes at radical prostatectomy (RP). A total of 300 patients with prostate specific antigen ≥ 3 ng/mL, PHI and prostate biopsy (71 patients with RP included) were retrospectively included in the study. The primary study outcomes are PCa and clinically significant PCa (csPCa, defined as ISUP GG ≥ 2) diagnostic rate of PHI, and GS upgrading rate at RP specimen. The secondary outcomes are the comparison between GS upgrading and non-upgrading group, GS upgrading and high-risk PCa (ISUP GG ≥ 3 or ≥ pT3a) predictability of preoperative clinical factors. Overall, 139 (46.3%) and 92 (30.7%) were diagnosed with PCa and csPCa, respectively. GS upgrading rate was 34.3% in all patients with RP. Significant differences were shown in the total prostate volume (p = 0.047), the distribution of ISUP GG at biopsy (p = 0.001) and RP (p = 0.032), respectively. PHI values ≥ 55 [Odds ratio (OR): 3.64 (95% confidence interval (CI) = 1.05–12.68, p = 0.042] and presence of PI-RADS lesion ≥ 4 (OR: 7.03, 95% CI = 1.68–29.51, p = 0.018) were the significant predictors of GS upgrading in RP specimens (AUC = 0.737). PHI values ≥ 55 (OR: 9.05, 5% CI = 1.04–78.52, p = 0.046) is a significant factor for predicting adverse pathologic features in RP specimens (AUC = 0.781). PHI could predict GS upgrading in combination with PIRADS lesions ≥ 4 in ISUP GG 1 & 2. PHI alone could evaluate the possibility of high-risk PCa after surgery as well.

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