Atezolizumab and Stereotactic Body Radiation in Metastatic, Recurrent, or Persistent Cervical Cancer: Results From a Phase 2 Multi-Institutional Study.

Background: Pembrolizumab is approved for PD-L1+ but not PD-L1 negative metastatic, recurrent, or persistent cervical cancer. Response rates to single agent anti-PD-1/PD-L1 therapy have been modest with no responses noted in PD-L1 negative tumors.

Methods And Materials: The study is designed as a prospective, phase II multi-institutional trial of stereotactic body radiation therapy (SBRT) followed by atezolizumab (1200 mg intravenously q3 weeks).

Impact of Intraoperative Blood Transfusions on Survival Rates in Ovarian Cancer Patients.

IntroductionOvarian cancer remains a leading cause of gynecologic cancer-related mortality worldwide. Identifying perioperative factors that influence survival outcomes is essential for optimizing care. This study evaluates the impact of perioperative factors such as intraoperative blood transfusions and hospital length of stay (LOS) on survival rates in ovarian cancer patients undergoing surgical debulking.

Vaccination with folate receptor-alpha peptides in patients with ovarian cancer following response to platinum-based therapy: A randomized, multicenter clinical trial.

Objective: Folate receptor alpha (FRα) is overexpressed on >90% of high-grade epithelial ovarian cancers (EOC). Targeting FRα with antibody-drug conjugates has proven utility in the platinum-resistant setting. It is also a potential therapeutic target for immuno-oncologic agents, such as peptide vaccines that work primarily via adaptive and humoral immunity.

To modulate or to skip: De-escalating PARP inhibitor maintenance therapy in ovarian cancer using adaptive therapy.

Toxicity and emerging drug resistance pose important challenges in poly-adenosine ribose polymerase inhibitor (PARPi) maintenance therapy of ovarian cancer. We propose that adaptive therapy, which dynamically reduces treatment based on the tumor dynamics, might alleviate both issues. Utilizing in vitro time-lapse microscopy and stepwise model selection, we calibrate and validate a differential equation mathematical model, which we leverage to test different plausible adaptive treatment schedules.

Preoperative and pre-chemotherapy CA-125 levels in high-risk early-stage ovarian cancer - An NRG/GOG study.

Objectives: To determine clinical significance of preoperative and pre-chemotherapy CA-125 in high-risk early-stage epithelial ovarian cancer patients.

Methods: All patients with stage IA/IB and grade 3, stage IC, clear cell, or completed resected stage II cancer were enrolled in a phase III trial and treated with chemotherapy. Kaplan-Meier method and Cox proportional hazards model were used for statistical analyses.

Prevalence of viral DNA in high-grade serous epithelial ovarian cancer and correlation with clinical outcomes.

Introduction: Currently 11 infectious agents are classified as carcinogenic but the role of infectious agents on outcomes of epithelial ovarian cancer is largely unknown.

Objective: To explore the association between infectious agents and ovarian cancer, we investigated the prevalence of viral DNA in primary ovarian cancer tumors and its association with clinical outcomes.

Methods: Archived tumors from 98 patients diagnosed with high-grade serous epithelial ovarian cancer were collected between 1/1/1994 and 12/31/2010.

A randomized phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer.

Objective: This phase 2 study investigated sapanisertib (selective dual inhibitor of mTORC1/2) alone, or in combination with paclitaxel or TAK-117 (a selective small molecule inhibitor of PI3K), versus paclitaxel alone in advanced, recurrent, or persistent endometrial cancer.

Methods: Patients with histologic diagnosis of endometrial cancer (1-2 prior regimens) were randomized to 28-day cycles on four treatment arms: 1) weekly paclitaxel 80 mg/m (days 1, 8, and 15); 2) weekly paclitaxel 80 mg/m + oral sapanisertib 4 mg on days 2-4, 9-11, 16-18, and 23-25; 3) weekly sapanisertib 30 mg, or 4) sapanisertib 4 mg + TAK-117 200 mg on days 1-3, 8-10, 15-17, and 22-24.

Results: Of 241 patients randomized, 234 received treatment (paclitaxel, n = 87 [3 ongoing]; paclitaxel+sapanisertib, n = 86 [3 ongoing]; sapanisertib, n = 41; sapanisertib+TAK-117, n = 20).

Relationships among Inflammatory Biomarkers and Objectively Assessed Physical Activity and Sleep during and after Chemotherapy for Gynecologic Malignancies.

Little is known regarding associations between inflammatory biomarkers and objectively measured physical activity and sleep during and after chemotherapy for gynecologic cancer; thus, we conducted a longitudinal study to address this gap. Women with gynecologic cancer (patients) and non-cancer controls (controls) completed assessments before chemotherapy cycles 1, 3, and 6 (controls assessed contemporaneously), as well as at 6- and 12-month follow-ups. Physical activity and sleep were measured using wrist-worn actigraphs and sleep diaries, and blood was drawn to quantify circulating levels of inflammatory markers.

Relationships among Inflammatory Biomarkers and Self-Reported Treatment-Related Symptoms in Patients Treated with Chemotherapy for Gynecologic Cancer: A Controlled Comparison.

Previous research suggests that inflammation triggers cancer-treatment-related symptoms (i.e., fatigue, depression, and disruptions in sleep and physical activity), but evidence is mixed.

Carboplatin dosing in the treatment of ovarian cancer: An NRG oncology group study.

Objective: To determine the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and explore adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl).

Methods: Retrospective data were obtained for 3830 of 4312 patients treated on GOG182 (NCT00011986)-a phase III trial of platinum-based chemotherapy for advanced-stage ovarian cancer. Carboplatin dose per patient on GOG182 was determined using the Jelliffe formula.

The effect of older age on treatment outcomes in women with advanced ovarian cancer receiving chemotherapy: An NRG-Oncology/Gynecologic Oncology Group (GOG-0182-ICON5) ancillary study.

Objective: To assess the effect of age on overall survival (OS) in women with ovarian cancer receiving chemotherapy. Secondary objectives were to describe the effect of age on treatment compliance, toxicities, progression free survival (PFS), time from surgery to chemotherapy, and rates of optimal cytoreduction.

Methods: Women enrolled in GOG 0182-ICON5 with stage III or IV epithelial ovarian cancer (EOC) who underwent surgery and chemotherapy between 2001 and 2004 were included.

Adaptive therapy for ovarian cancer: An integrated approach to PARP inhibitor scheduling.

Toxicity and emerging drug resistance are important challenges in PARP inhibitor (PARPi) treatment of ovarian cancer. Recent research has shown that evolutionary-inspired treatment algorithms which adapt treatment to the tumor's treatment response (adaptive therapy) can help to mitigate both. Here, we present a first step in developing an adaptive therapy protocol for PARPi treatment by combining mathematical modelling and wet-lab experiments to characterize the cell population dynamics under different PARPi schedules.

Randomized phase II trial of farletuzumab plus chemotherapy versus placebo plus chemotherapy in low CA-125 platinum-sensitive ovarian cancer.

Objective: The primary purpose of this study was to determine if farletuzumab, an antifolate receptor-α monoclonal antibody, improved progression-free survival (PFS) versus placebo when added to standard chemotherapy regimens in patients with platinum-sensitive recurrent ovarian cancer (OC) in first relapse (platinum-free interval: 6-36 months) with low cancer antigen 125 (CA-125) levels.

Methods: Eligibility included CA-125 ≤ 3 x upper limit of normal (ULN, 105 U/mL), high-grade serous, platinum-sensitive recurrent OC, previous treatment with debulking surgery, and first-line platinum-based chemotherapy with 1st recurrence between 6 and 36 months since frontline platinum-based treatment. Patients received investigator's choice of either carboplatin (CARBO)/paclitaxel (PTX) every 3 weeks or CARBO/pegylated liposomal doxorubicin (PLD) every 4 weeks x6 cycles in combination with either farletuzumab [5 mg/kg weekly] or placebo randomized in a 2:1 ratio.

The clinical and prognostic significance of pre-chemotherapy serum CA-125 in high-risk early stage ovarian cancer: An NRG/GOG ancillary study.

Objectives: To determine the clinical and prognostic significance of CA-125 trends prior to, during, and after chemotherapy in high-risk early-stage epithelial ovarian cancer patients.

Methods: All patients were enrolled in a phase III randomized trial (GOG 157) following upfront surgery for grade 3 stage IA/IB, stage IC, or stage II disease, and had been treated with either three or six cycles of carboplatin/paclitaxel. Kaplan-Meier method and Cox proportional hazards model were used to evaluate recurrence-free survival (RFS) and overall survival (OS).

A Phase III Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor-Positive Ovarian Cancer (Study 006).

Purpose: The adjunctive use of intraoperative molecular imaging (IMI) is gaining acceptance as a potential means to improve outcomes for surgical resection of targetable tumors. This confirmatory study examined the use of pafolacianine for real-time detection of folate receptor-positive ovarian cancer.

Methods: This phase III, open-label, 11-center study included subjects with known or suspected ovarian cancer, scheduled to undergo cytoreductive surgery.

Prognostic features of endometrial cancer metastasis to the central nervous system.

Objectives: Central nervous system metastases (CNSm) secondary to endometrial cancer (EC) are rare. As a result, prognostic factors for this patient population are not well described.

Methods: EC patients with CNSm were identified retrospectively from two academic centers.

Olfactory Receptor OR2H1 Is an Effective Target for CAR T Cells in Human Epithelial Tumors.

Although chimeric antigen receptor (CAR)-expressing T cells have proven success in hematologic malignancies, their effectiveness in solid tumors has been largely unsuccessful thus far. We found that some olfactory receptors are expressed in a variety of solid tumors of different histologic subtypes, with a limited pattern of expression in normal tissues. Quantification of OR2H1 expression by qRT-PCR and Western blot analysis of 17 normal tissues, 82 ovarian cancers of various histologies, eight non-small cell lung cancers (NSCLCs), and 17 breast cancers demonstrated widespread OR2H1 expression in solid epithelial tumors with expression in normal human tissues limited to the testis.

The impact of distance to closest negative margin on survival after pelvic exenteration.

Objective: To determine the effect of distance to closest negative margin on survival after pelvic exenteration (PE).

Methods: In this retrospective analysis of PE at Moffitt Cancer Center from 2000 to 2019, baseline characteristics, clinical details, and outcomes were ascertained. Distance to closest negative margin was measured.

Phase Ib Study of Navicixizumab Plus Paclitaxel in Patients With Platinum-Resistant Ovarian, Primary Peritoneal, or Fallopian Tube Cancer.

Purpose: This phase Ib study evaluated the safety and efficacy of paclitaxel plus navicixizumab, a bispecific antiangiogenic antibody to vascular endothelial growth factor and delta-like ligand 4, against platinum-resistant ovarian cancer.

Patients And Methods: This open-label, nonrandomized, dose-escalation and -expansion study included 44 patients with previously treated, recurrent, platinum-resistant grade 2/3 ovarian cancer. Treatment was intravenous navicixizumab (3 mg/kg or 4 mg/kg once every 2 weeks) plus paclitaxel (80 mg/m intravenously on days 0, 7, and 14 of 28-day cycles).

Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells.

Despite repeated associations between T cell infiltration and outcome, human ovarian cancer remains poorly responsive to immunotherapy. We report that the hallmarks of tumor recognition in ovarian cancer-infiltrating T cells are primarily restricted to tissue-resident memory (TRM) cells. Single-cell RNA/TCR/ATAC sequencing of 83,454 CD3CD8CD103CD69 TRM cells and immunohistochemistry of 122 high-grade serous ovarian cancers shows that only progenitor (TCF1) tissue-resident T cells (TRM cells), but not recirculating TCF1 T cells, predict ovarian cancer outcome.