Concurrent Chemotherapy and Pelvic Radiation Therapy Compared With Pelvic Radiation Therapy Alone as Adjuvant Therapy After Radical Surgery in High-Risk Early-Stage Cancer of the Cervix.

Purpose: To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma.

Patients And Methods: Patients with clinical stage IA, IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT.

Sustained Response with Dose-reduced Selpercatinib in a Pediatric Patient with Metastatic NCOA4-RET Fusion Papillary Thyroid Carcinoma.

Understanding the molecular landscape of papillary thyroid carcinoma (PTC), the most common thyroid cancer in children, creates additional therapeutic approaches. RET gene rearrangements are observed in pediatric PTC, and selective inhibition of RET is now possible with specific tyrosine kinase inhibitors designed to target diverse RET -activating alterations. We present a 13-year-old female with metastatic PTC, clinically resistant to radioactive iodine, and found to harbor a NCOA4-RET fusion.

SCCA1/SERPINB3 suppresses antitumor immunity and blunts therapy-induced T cell responses via STAT-dependent chemokine production.

Patients with cancer who have high serum levels of squamous cell carcinoma antigen 1 (SCCA1, now referred to as SERPINB3) commonly experience treatment resistance and have a poor prognosis. Despite being a clinical biomarker, the modulation of SERPINB3 in tumor immunity is poorly understood. We found positive correlations of SERPINB3 with CXCL1, CXCL8 (CXCL8/9), S100A8, and S100A9 (S100A8/A9) myeloid cell infiltration through RNA-Seq analysis of human primary cervical tumors.

SCCA1/SERPINB3 promotes suppressive immune environment via STAT-dependent chemokine production, blunting the therapy-induced T cell responses.

Radiotherapy is a commonly used cancer treatment; however, patients with high serum squamous cell carcinoma antigen (SCCA1/SERPINB3) are associated with resistance and poor prognosis. Despite being a strong clinical biomarker, the modulation of SERPINB3 in tumor immunity is poorly understood. We investigated the microenvironment of SERPINB3 high tumors through RNAseq of primary cervix tumors and found that was positively correlated with and myeloid cell infiltration.

Overall survival in patients with FIGO stage IVA cervical cancer.

Objective: FIGO stage IVA cervical cancer is a unique diagnosis that conveys a poor prognosis. Despite the use of PET/CT for staging, concurrent chemotherapy, and image-guided brachytherapy, overall survival (OS) in these patients is low. Treatment requires aggressive use of radiotherapy and chemotherapy.

Management and prognosis of cervical cancer patients treated with definitive radiation therapy who have partial metabolic response on post-therapy positron emission tomography.

Objective: To describe the management and outcomes of cervical cancer patients initially treated with radiation who had partial metabolic response (PMR) on three-month post-radiation F-fluorodeoxyglucose positron emissions tomography (FDG-PET).

Methods: Cervical cancer patients treated with radiation between 1997 and 2013 who had PMR on initial post-therapy FDG-PET were identified from a prospectively maintained database. Descriptive statistics were used to summarize patient demographics, tumor characteristics, surveillance methods, and treatment modalities.

The impact of tumor size and histology on local control when utilizing high-dose-rate interstitial brachytherapy for gynecologic malignancies.

Objective: To report long-term results of an outpatient template-based high-dose-rate interstitial brachytherapy (HDR ISBT) program for the treatment of gynecologic malignancies.

Methods: Patients treated between 2006 and 2020 at an academic hospital with outpatient template based HDR ISBT without spinal or general anesthesia were reviewed. Patients who had previously received HDR ISBT were excluded.

Expression of Potential Biomarker Targets by Immunohistochemistry in Cervical Carcinomas.

There have been few clinically useful targetable biomarkers in uterine cervical carcinomas. Estrogen receptor (ER), HER2, and fibroblast activation protein (FAP) are potential therapeutic or theranostic targets in other gynecologic and genitourinary carcinoma types. We determined the immunohistochemical expression patterns of these markers in treatment-naive cervical carcinoma, and whether expression correlated with clinical outcomes after definitive chemoradiation therapy.

SERPINB3 (SCCA1) inhibits cathepsin L and lysoptosis, protecting cervical cancer cells from chemoradiation.

The endogenous lysosomal cysteine protease inhibitor SERPINB3 (squamous cell carcinoma antigen 1, SCCA1) is elevated in patients with cervical cancer and other malignancies. High serum SERPINB3 is prognostic for recurrence and death following chemoradiation therapy. Cervical cancer cells genetically lacking SERPINB3 are more sensitive to ionizing radiation (IR), suggesting this protease inhibitor plays a role in therapeutic response.

Genomic Characterization and Therapeutic Targeting of HPV Undetected Cervical Carcinomas.

Cervical cancer tumors with undetectable HPV (HPV) have been underappreciated in clinical decision making. In this study, two independent CC datasets were used to characterize the largest cohort of HPV tumors to date (HPV = 35, HPV = 430). Genomic and transcriptome tumor profiles and patient survival outcomes were compared between HPV and HPV tumors.

Phase I Trial of Stereotactic MRI-Guided Online Adaptive Radiation Therapy (SMART) for the Treatment of Oligometastatic Ovarian Cancer.

Purpose: Stereotactic body radiation therapy is increasingly used to treat a variety of oligometastatic histologies, but few data exist for ovarian cancer. Ablative stereotactic body radiation therapy dosing is challenging in sites like the abdomen, pelvis, and central thorax due to proximity and motion of organs at risk. A novel radiation delivery method, stereotactic magnetic-resonance-guided online-adaptive radiation therapy (SMART), may improve the therapeutic index of stereotactic body radiation therapy through enhanced soft-tissue visualization, real-time nonionizing imaging, and ability to adapt to the anatomy-of-the-day, with the goal of producing systemic-therapy-free intervals.

HPV transcript expression affects cervical cancer response to chemoradiation.

Persistent HPV infection is causative for the majority of cervical cancer cases; however, current guidelines do not require HPV testing for newly diagnosed cervical cancer. Using an institutional cohort of 88 patients with cervical cancer treated uniformly with standard-of-care chemoradiation treatment (CRT) with prospectively collected clinical outcome data, we observed that patients with cervical tumors containing HPV genotypes other than HPV 16 have worse survival outcomes after CRT compared with patients with HPV 16+ tumors, consistent with previously published studies. Using RNA sequencing analysis, we quantified viral transcription efficiency and found higher levels of E6 and the alternative transcript E6*I in cervical tumors with HPV genotypes other than HPV 16.

Standardized Uptake Value for F-Fluorodeoxyglucose Is a Marker of Inflammatory State and Immune Infiltrate in Cervical Cancer.

Purpose: Chemoradiotherapy for locally advanced cervical cancer fails in over a third of patients. Biomarkers with therapeutic implications are therefore needed. We investigated the relationship between an established prognostic marker, maximum standardized uptake value (SUV) on F-fluorodeoxyglucose positron emission tomography, and the inflammatory and immune state of cervical cancers.

Targetability of cervical cancer by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-mediated hyperthermia (HT) for patients receiving radiation therapy.

Purpose: To evaluate the targetability of late-stage cervical cancer by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-induced hyperthermia (HT) as an adjuvant to radiation therapy (RT).

Methods: Seventy-nine cervical cancer patients (stage IIIB-IVA) who received RT with lesions visible on positron emission tomography-computed tomography (PET-CT) were retrospectively analyzed for targetability using a commercially-available HT-capable MRgHIFU system. Targetability was assessed for both primary targets and/or any metastatic lymph nodes using both posterior (supine) and anterior (prone) patient setups relative to the transducer.

Integrating imaging and RNA-seq improves outcome prediction in cervical cancer.

Approaches using a single type of data have been applied to classify human tumors. Here we integrate imaging features and transcriptomic data using a prospectively collected tumor bank. We demonstrate that increased maximum standardized uptake value on pretreatment 18F-fluorodeoxyglucose-positron emission tomography correlates with epithelial-to-mesenchymal transition (EMT) gene expression.

Localized Delivery of Cisplatin to Cervical Cancer Improves Its Therapeutic Efficacy and Minimizes Its Side Effect Profile.

Purpose: Cervical cancer represents the fourth most frequent malignancy in the world among women, and mortality has remained stable for the past 4 decades. Intravenous cisplatin with concurrent radiation therapy is the standard-of-care for patients with local and regional cervical cancer. However, cisplatin induces serious dose-limiting systemic toxicities and recurrence frequently occurs.

Repeatability of F-FDG PET Radiomic Features in Cervical Cancer.

Knowledge of the intrinsic variability of radiomic features is essential to the proper interpretation of changes in these features over time. The primary aim of this study was to assess the test-retest repeatability of radiomic features extracted from F-FDG PET images of cervical tumors. The impact of different image preprocessing methods was also explored.

Early posttherapy clearance of human papillomavirus and treatment response in cervical carcinoma.

Background: Among patients with cervical cancer, little is known about the significance of persistent human papillomavirus (HPV) expression after chemoradiation (CRT). This study evaluated associations between early posttreatment HPV clearance and patient outcomes with an added focus on the value of posttherapy positron emission tomography (PET) imaging.

Methods: Included patients underwent pretreatment testing indicating a high-risk HPV infection and posttreatment testing with a messenger RNA (mRNA)-based genital swab after CRT.

Radiologic Assessment of Groin Lymph Nodes in Pelvic Malignancies.

Introduction: Metastatic involvement of groin nodes can alter radiation therapy planning for pelvic tumors. F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) can identify nodal metastases; however, interpretation of PET/CT-positive nodes can be complicated by non-malignant processes. We evaluated quantitative metrics as methods to identify groin metastases in patients with pelvic tumors by comparison with standard subjective interpretive criteria, with pathology as the reference standard.

FIGO 2018 staging criteria for cervical cancer: Impact on stage migration and survival.

Objective: To compare FIGO 2009 and FIGO 2018 cervical cancer staging criteria with a focus on stage migration and treatment outcomes.

Methods: This study is based on a database cohort of 1282 patients newly diagnosed with cervical cancer from 1997 to 2019. All underwent standard clinical examination and whole-body FDG-PET.

Treatment Outcome Prediction for Cancer Patients based on Radiomics and Belief Function Theory.

In this study, we proposed a new radiomics-based treatment outcome prediction model for cancer patients. The prediction model is developed based on belief function theory (BFT) and sparsity learning to address the challenges of redundancy, heterogeneity, and uncertainty of radiomic features, and relatively small-sized and unbalanced training samples. The model first selects the most predictive feature subsets from relatively large amounts of radiomic features extracted from pre- and/or in-treatment positron emission tomography (PET) images and available clinical and demographic features.

Decreased local immune response and retained HPV gene expression during chemoradiotherapy are associated with treatment resistance and death from cervical cancer.

More than one-third of patients with locally advanced cervical cancer do not respond to chemoradiation therapy (CRT). We aimed to characterize the transcriptional landscape of paired human cervical tumors before and during CRT in order to gain insight into the evolution of treatment response and to elucidate mechanisms of treatment resistance. We prospectively collected cervical tumor biopsies from 115 patients both before and 3 weeks into CRT.

Molecular Imaging for Radiotherapy Planning and Response Assessment for Cervical Cancer.

Positron emission tomography (PET) with [F]fluorodeoxyglucose (FDG) leverages imaging contrast from accelerated and aberrant glucose metabolism, which is a hallmark of cancer. FDG-PET is essential for assessing involved lymph nodes and distant metastases for cervical cancer. It is also utilized for target delineation in radiation treatment planning, with investigations into functional bone marrow sparing intensity modulated radiation therapy.