Leveraging radiomics and machine learning to differentiate radiation necrosis from recurrence in patients with brain metastases.

OBJECTIVE: Radiation necrosis (RN) can be difficult to radiographically discern from tumor progression after stereotactic radiosurgery (SRS). The objective of this study was to investigate the utility of radiomics and machine learning (ML) to differentiate RN from recurrence in patients with brain metastases treated with SRS. METHODS: Patients with brain metastases treated with SRS who developed either RN or tumor reccurence were retrospectively identified. Image preprocessing and radiomic feature extraction were performed using ANTsPy and PyRadiomics, yielding 105 features from MRI T1-weighted post-contrast (T1c), T2, and fluid-attenuated inversion recovery (FLAIR) images. Univariate analysis assessed significance of individual features. Multivariable analysis employed various classifiers on features identified as most discriminative through feature selection. ML models were evaluated through cross-validation, selecting the best model based on area under the receiver operating characteristic (ROC) curve (AUC). Specificity, sensitivity, and F1 score were computed. RESULTS: Sixty-six lesions from 55 patients were identified. On univariate analysis, 27 features from the T1c sequence were statistically significant, while no features were significant from the T2 or FLAIR sequences. For clinical variables, only immunotherapy use after SRS was significant. Multivariable analysis of features from the T1c sequence yielded an AUC of 76.2% (standard deviation [SD] ± 12.7%), with specificity and sensitivity of 75.5% (± 13.4%) and 62.3% (± 19.6%) in differentiating radionecrosis from recurrence. CONCLUSIONS: Radiomics with ML may assist the diagnostic ability of distinguishing RN from tumor recurrence after SRS. Further work is needed to validate this in a larger multi-institutional cohort and prospectively evaluate it's utility in patient care.

Treatment of Oligometastatic GI Cancers.

Oligometastatic state is believed to potentially represent a transitional stage between early, locoregional state disease and widely metastatic disease. Historically, locoregional approaches, particularly in advanced colorectal cancers, have demonstrated efficacy in select patients with limited burden of metastatic disease. Recent strides in systemic therapies, including biomarker-based treatments and immunotherapy, alongside innovations in surgical techniques and novel locoregional approaches such as stereotactic radiotherapy and ablation, have ushered in a new era of therapeutic possibilities across all oligometastatic GI cancers. Despite these advancements, there remains a significant gap in high-quality prospective evidence guiding patient selection and treatment decisions across various disease types. Ongoing clinical trials are anticipated to provide crucial insights into oligometastatic states, fostering the refinement of disease-specific oligometastatic state definitions and treatment algorithms. This article reviews existing data on the management of oligometastatic GI cancer, summarizes current state of knowledge for each disease state, and provides updates on ongoing studies in this space.

Prediction of Rapid Early Progression and Survival Risk with Pre-Radiation MRI in WHO Grade 4 Glioma Patients.

Recent clinical research describes a subset of glioblastoma patients that exhibit REP prior to the start of radiation therapy. Current literature has thus far described this population using clinicopathologic features. To our knowledge, this study is the first to investigate the potential of conventional radiomics, sophisticated multi-resolution fractal texture features, and different molecular features (MGMT, IDH mutations) as a diagnostic and prognostic tool for prediction of REP from non-REP cases using computational and statistical modeling methods. The radiation-planning T1 post-contrast (T1C) MRI sequences of 70 patients are analyzed. An ensemble method with 5-fold cross-validation over 1000 iterations offers an AUC of 0.793 ± 0.082 for REP versus non-REP classification. In addition, copula-based modeling under dependent censoring (where a subset of the patients may not be followed up with until death) identifies significant features (p-value < 0.05) for survival probability and prognostic grouping of patient cases. The prediction of survival for the patients' cohort produces a precision of 0.881 ± 0.056. The prognostic index (PI) calculated using the fused features shows that 84.62% of REP cases fall under the bad prognostic group, suggesting the potential of fused features for predicting a higher percentage of REP cases. The experimental results further show that multi-resolution fractal texture features perform better than conventional radiomics features for prediction of REP and survival outcomes.

Progressive Global Ataxia With Sensory Changes as a Paraneoplastic Syndrome in a Patient With Chromophobe Renal Cell Carcinoma.

Paraneoplastic syndromes (PNS) are rare and can be challenging to diagnose and treat. The uniqueness of PNS lies in the complexity of presentation, the importance of early diagnosis, and the role of multidisciplinary care in managing those patients to mitigate long-term neurologic complications. We describe a patient with metastatic renal cell carcinoma who presented with a complex constellation of neurological symptoms (progressive global ataxia and sensory changes) that did not resolve following nephrectomy. While complete resolution of symptoms was not achieved, he did have stabilization of his neurologic decline with the initiation of cancer-directed therapies.

Comprehensive Review of Molecular Mechanisms and Clinical Features of Invasive Lobular Cancer.

Invasive lobular carcinoma (ILC) accounts for 10% to 15% of breast cancers in the United States, 80% of which are estrogen receptor (ER)-positive, with an unusual metastatic pattern of spread to sites such as the serosa, meninges, and ovaries, among others. Lobular cancer presents significant challenges in detection and clinical management given its multifocality and multicentricity at presentation. Despite the unique features of ILC, it is often lumped with hormone receptor-positive invasive ductal cancers (IDC); consequently, ILC screening, treatment, and follow-up strategies are largely based on data from IDC. Despite both being treated as ER-positive breast cancer, querying the Cancer Genome Atlas database shows distinctive molecular aberrations in ILC compared with IDC, such as E-cadherin loss (66% vs. 3%), FOXA1 mutations (7% vs. 2%), and GATA3 mutations (5% vs. 20%). Moreover, compared with patients with IDC, patients with ILC are less likely to undergo breast-conserving surgery, with lower rates of complete response following therapy as these tumors are less chemosensitive. Taken together, this suggests that ILC is biologically distinct, which may influence tumorigenesis and therapeutic strategies. Long-term survival and clinical outcomes in patients with ILC are worse than in stage- and grade-matched patients with IDC; therefore, nuanced criteria are needed to better define treatment goals and protocols tailored to ILC's unique biology. This comprehensive review highlights the histologic and clinicopathologic features that distinguish ILC from IDC, with an in-depth discussion of ILC's molecular alterations and biomarkers, clinical trials and treatment strategies, and future targets for therapy. IMPLICATIONS FOR PRACTICE: The majority of invasive lobular breast cancers (ILCs) are hormone receptor (HR)-positive and low grade. Clinically, ILC is treated similar to HR-positive invasive ductal cancer (IDC). However, ILC differs distinctly from IDC in its clinicopathologic characteristics and molecular alterations. ILC also differs in response to systemic therapy, with studies showing ILC as less sensitive to chemotherapy. Patients with ILC have worse clinical outcomes with late recurrences. Despite these differences, clinical trials treat HR-positive breast cancers as a single disease, and there is an unmet need for studies addressing the unique challenges faced by patients diagnosed with ILC.

Abrupt involution induces inflammation, estrogenic signaling, and hyperplasia linking lack of breastfeeding with increased risk of breast cancer.

BACKGROUND: A large collaborative analysis of data from 47 epidemiological studies concluded that longer duration of breastfeeding reduces the risk of developing breast cancer. Despite the strong epidemiological evidence, the molecular mechanisms linking prolonged breastfeeding to decreased risk of breast cancer remain poorly understood. METHODS: We modeled two types of breastfeeding behaviors in wild type FVB/N mice: (1) normal or gradual involution of breast tissue following prolonged breastfeeding and (2) forced or abrupt involution following short-term breastfeeding. To accomplish this, pups were gradually weaned between 28 and 31 days (gradual involution) or abruptly at 7 days postpartum (abrupt involution). Mammary glands were examined for histological changes, proliferation, and inflammatory markers by immunohistochemistry. Fluorescence-activated cell sorting was used to quantify mammary epithelial subpopulations. Gene set enrichment analysis was used to analyze gene expression data from mouse mammary luminal progenitor cells. Similar analysis was done using gene expression data generated from human breast samples obtained from parous women enrolled on a tissue collection study, OSU-2011C0094, and were undergoing reduction mammoplasty without history of breast cancer. RESULTS: Mammary glands from mice that underwent abrupt involution exhibited denser stroma, altered collagen composition, higher inflammation and proliferation, increased estrogen receptor α and progesterone receptor expression compared to those that underwent gradual involution. Importantly, when aged to 4 months postpartum, mice that were in the abrupt involution cohort developed ductal hyperplasia and squamous metaplasia. Abrupt involution also resulted in a significant expansion of the luminal progenitor cell compartment associated with enrichment of Notch and estrogen signaling pathway genes. Breast tissues obtained from healthy women who breastfed for < 6 months vs ≥ 6 months showed significant enrichment of Notch signaling pathway genes, along with a trend for enrichment for luminal progenitor gene signature similar to what is observed in BRCA1 mutation carriers and basal-like breast tumors. CONCLUSIONS: We report here for the first time that forced or abrupt involution of the mammary glands following pregnancy and lack of breastfeeding results in expansion of luminal progenitor cells, higher inflammation, proliferation, and ductal hyperplasia, a known risk factor for developing breast cancer.

miR-29b defines the pro-/anti-proliferative effects of S100A7 in breast cancer.

INTRODUCTION: S100A7 (Psoriasin) is an inflammatory protein known to be upregulated in breast cancer. However, the role of S100A7 in breast cancer has been elusive, since both pro- and anti-proliferative roles have been reported in different types of breast cancer cells and animal models. To date, the mechanism by which S100A7 differentially regulates breast cancer cell proliferation is still not clear. METHODS: We used Gene Functional Enrichment Analysis to search for the determining factor of S100A7 differential regulation. We confirmed the factor and elaborated its regulating mechanism using in vitro cell culture. We further verified the findings using xenografts of human breast cancer cells in nude mice. RESULTS: In the present study, we show that S100A7 significantly upregulates the expression of miR-29b in Estrogen Receptor (ER)-positive breast cancer cells (represented by MCF7), and significantly downregulates miR-29b in ER-negative cells (represented by MDA-MB-231) [Corrected]. The differential regulation of miR-29b by S100A7 in ER-positive and ER-negative breast cancer is supported by the gene expression analysis of TCGA invasive breast cancer dataset. miR-29b transcription is inhibited by NF-κB, and NF-κB activation is differentially regulated by S100A7 in ER-positive and ER-negative breast cancer cells. This further leads to differential regulation of PI3K p85α and CDC42 expression, p53 activation and p53-associated anti-proliferative pathways. Reversing the S100A7-caused changes of miR-29b expression by transfecting exogenous miR-29b or miR-29b-Decoy can inhibit the effects of S100A7 on in vitro cell proliferation and tumor growth in nude mice. CONCLUSIONS: The distinct modulations of the NF-κB - miR-29b - p53 pathway make S100A7 an oncogene in ER-negative and a cancer-suppressing gene in ER-positive breast cancer cells, with miR-29b being the determining regulatory factor.