Faculty Bibliography
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119
Effectiveness and toxicity of five-fraction prone accelerated partial breast irradiation
PURPOSE/OBJECTIVE:Our institution was an early adopter of 5-fraction accelerated partial breast irradiation (ABPI) to treat women with early-stage breast cancer. This study reports long-term oncologic and cosmetic outcomes. METHODS:We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Logistic regression models were used to identify factors associated with development of late toxicities, clinician, and patient-rated cosmesis. Kaplan-Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free survival (LR-RFS). RESULTS:442 patients received APBI either daily (56%) or every other day (44%) in the prone position (92%). At a median follow-up of 48 months (range: 5.96-155 months), 12 (2.7%) patients developed a local recurrence (LR). Out of 258 patients with > 3-month toxicity data available, the most common late grade ≥ 2 adverse event was breast fibrosis (6.2%). On multivariate analysis, daily APBI treatment (vs every other day) did not correlate with an increased risk of any late grade ≥ 2 toxicity though it did correlate with a lower risk of any late grade ≥ 2 fibrosis. Overall, at a median follow-up of 80 months, the rates of good-excellent physician and patient-rated cosmesis were 95% and 85%, respectively, with no difference between patients treated on consecutive vs. every other day. On multivariate analysis, patients who did not receive any adjuvant therapy were at increased risk of developing a LR. Five-year OS, LRFS, and DFS were 97.2%, 97.7%, and 89.5%, respectively. CONCLUSIONS:Five-fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity, and excellent cosmesis at long-term follow-up.
PMID: 38183516
ISSN: 1573-7217
CID: 5644242
Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer
Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
PMID: 38230434
ISSN: 1096-9896
CID: 5633182
Effectiveness and toxicity of five-fraction prone accelerated partial breast irradiation
Purpose: Our institution was an early adopter of 5-fraction accelerated partial breast irradiation (ABPI) to treat women with early-stage breast cancer. This study reports long-term oncologic and cosmetic outcomes. Methods: We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Logistic regression models were used to identify factors associated with development of late toxicities, clinician, and patient-rated cosmesis. Kaplan"“Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free survival (LR-RFS). Results: 442 patients received APBI either daily (56%) or every other day (44%) in the prone position (92%). At a median follow-up of 48 months (range: 5.96"“155 months), 12 (2.7%) patients developed a local recurrence (LR). Out of 258 patients with > 3-month toxicity data available, the most common late grade ≥ 2 adverse event was breast fibrosis (6.2%). On multivariate analysis, daily APBI treatment (vs every other day) did not correlate with an increased risk of any late grade ≥ 2 toxicity though it did correlate with a lower risk of any late grade ≥ 2 fibrosis. Overall, at a median follow-up of 80 months, the rates of good"“excellent physician and patient-rated cosmesis were 95% and 85%, respectively, with no difference between patients treated on consecutive vs. every other day. On multivariate analysis, patients who did not receive any adjuvant therapy were at increased risk of developing a LR. Five-year OS, LRFS, and DFS were 97.2%, 97.7%, and 89.5%, respectively. Conclusions: Five-fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity, and excellent cosmesis at long-term follow-up.
SCOPUS:85181487903
ISSN: 0167-6806
CID: 5630272
Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer
Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
SCOPUS:85182480446
ISSN: 0022-3417
CID: 5629662
Long-term Survival From Breast Cancer Brain Metastases in the Era of Modern Systemic Therapies
BACKGROUND AND OBJECTIVES/OBJECTIVE:Median survival for all patients with breast cancer with brain metastases (BCBMs) has increased in the era of targeted therapy (TT) and with improved local control of intracranial tumors using stereotactic radiosurgery (SRS) and surgical resection. However, detailed characterization of the patients with long-term survival in the past 5 years remains sparse. The aim of this article is to characterize patients with BCBM who achieved long-term survival and identify factors associated with the uniquely better outcomes and to find predictors of mortality for patients with BCBM. METHODS:We reviewed 190 patients with breast cancer with 931 brain tumors receiving SRS who were followed at our institution with prospective data collection between 2012 and 2022. We analyzed clinical, molecular, and imaging data to assess relationship to outcomes and tumor control. RESULTS:The median overall survival from initial SRS and from breast cancer diagnosis was 25 months (95% CI 19-31 months) and 130 months (95% CI 100-160 months), respectively. Sixteen patients (17%) achieved long-term survival (survival ≥5 years from SRS), 9 of whom are still alive. Predictors of long-term survival included HER2+ status ( P = .041) and treatment with TT ( P = .046). A limited number of patients (11%) died of central nervous system (CNS) causes. A predictor of CNS-related death was the development of leptomeningeal disease after SRS ( P = .025), whereas predictors of non-CNS death included extracranial metastases at first SRS ( P = .017), triple-negative breast cancer ( P = .002), a Karnofsky Performance Status of <80 at first SRS ( P = .002), and active systemic disease at last follow-up ( P = .001). Only 13% of patients eventually needed whole brain radiotherapy. Among the long-term survivors, none died of CNS progression. CONCLUSION/CONCLUSIONS:Patients with BCBM can achieve long-term survival. The use of TT and HER2+ disease are associated with long-term survival. The primary cause of death was extracranial disease progression, and none of the patients living ≥5 years died of CNS-related disease.
PMID: 37581437
ISSN: 1524-4040
CID: 5599542
Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer
The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
PMCID:10518802
PMID: 37608772
ISSN: 1096-9896
CID: 5598512
Spatial analyses of immune cell infiltration in cancer: current methods and future directions: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer
Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based). We then provide a compendium of spatial immune cell metrics that have been reported in the literature, summarizing prognostic associations in the context of a variety of cancers. We conclude by discussing two well-described clinical biomarkers, the breast cancer stromal tumor infiltrating lymphocytes score and the colon cancer Immunoscore, and describe investigative opportunities to improve clinical utility of these spatial biomarkers. © 2023 The Pathological Society of Great Britain and Ireland.
PMID: 37608771
ISSN: 1096-9896
CID: 5598482
A Case of Pathologic Complete Response to Neoadjuvant Chemotherapy and Pembrolizumab in Metaplastic Breast Cancer [Case Report]
PMID: 37196220
ISSN: 2473-4284
CID: 5508012
Association Between Biomarkers and Clinical Outcomes of Pembrolizumab Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer: KEYNOTE-086 Exploratory Analysis
PURPOSE/OBJECTIVE:In the two-cohort phase II KEYNOTE-086 study (ClinicalTrials.gov identifier: NCT02447003), first-line and second-line or later pembrolizumab monotherapy demonstrated antitumor activity in metastatic triple-negative breast cancer (mTNBC; N = 254). This exploratory analysis evaluates the association between prespecified molecular biomarkers and clinical outcomes. METHODS:values were calculated, and significance was prespecified at α = 0.05. RESULTS:GEP. CONCLUSION/CONCLUSIONS:GEP were associated with improved clinical outcomes of pembrolizumab and may help identify patients with mTNBC who are most likely to respond to pembrolizumab monotherapy.
PMID: 37099733
ISSN: 2473-4284
CID: 5465142
International journal of gynecological cancer. 2022:Conference:(International):A228-A229.DOI: 10.1136/ijgc-2022-igcs.521
XMT-1660: A PHASE 1B TRIAL OF A B7-H4 TARGETING ANTIBODY DRUG CONJUGATE (ADC) IN ENDOMETRIAL, OVARIAN, AND BREAST CANCERS [Meeting Abstract]
Objectives Endometrial (EC) and ovarian cancers (OC) are some of the leading causes of cancer death in women. Despite therapeutic advances, many patients eventually develop resistance to available standard of care (SOC) therapies. B7-H4 is a poor prognostic factor and is overexpressed in several cancers including endometrial, ovarian, and breast. As a member of the CD28/B7 family of cell surface proteins, it promotes tumorigenesis by suppressing anti-tumor immunity XMT-1660 is a B7-H4-targeted Dolasynthen ADC with a precise, optimized drug-to-antibody ratio and a DolaLock microtubule inhibitor payload with controlled bystander effect. In the preclinical setting, XMT-1660 has demonstrated anti-tumor activity in EC and OC PDX models. Methods The Ph1 trial includes a first-in-human dose escalation (DES) portion followed by a dose expansion (EXP) evaluating XMT-1660 in patients with EC, OC, and BC following progression on SOC. In the DES, BOIN design will be used to determine the MTD. The DES will assess safety and preliminary efficacy, and establish recommended phase 2 dose (RP2D). In the EXP portion, cohorts enrolling EC/OC, TNBC, ER+/HER2- BC, are planned and additional patients may be enrolled based on emerging data. The primary endpoints are safety and tolerability, overall response rate, disease control rate, and duration of response. Patients are not selected by B7-H4 status but baseline tumors samples are collected for retrospective analysis. The trial is currently enrolling patients. NCT05377996 Results Trial in progress Conclusions Trial in progress
EMBASE:639890110
ISSN: 1525-1438
CID: 5512592
