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Purpose This study sought to determine the relationship between cervical cancer recurrence and post-treatment change in standardized uptake value (SUV) of 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in the cervix and lymph nodes. Methods This retrospective cohort study included patients who received curative intent radiation therapy for biopsy-proven stage I–IVA locally advanced cervical cancer at a single tertiary referral center from 2009 to 2021. The exposure was percent change in SUV from pre- to post-treatment FDG-PET scans at the cervix and lymph nodes. The primary outcome was recurrence rate, and secondary outcomes were overall and progression-free survival. Firth’s penalized logistic regression and Cox proportional hazards models were used to assess associations. Results 55 patients met eligibility criteria. Recurrence rate was 27% (15/55); of these, 33% had local recurrence (5/55) and 67% had distant recurrence (10/55). Median percent decrease of cervical SUV after treatment in those with and without recurrence was similar (71.4 vs 68.8, p  = 0.89); this remained consistent when analyzing those with local recurrence only (70.5, p  = 0.95). When the percent decrease in cervical SUV was examined in intervals (< 25%, 25–50%, 50–75%, > 75%), this was also not predictive of local ( p  = 0.91) or overall ( p  = 0.75) recurrence. Median percent decrease at the most avid and distant lymph node in those with and without recurrence was not significantly different ( p  > 0.05). Neither change in cervical nor lymph node SUV was associated with overall or progression-free survival. Conclusion Changes in SUV after treatment may not be a reliable stand-alone marker for predicting recurrence or survival in locally advanced cervical cancer after treatment with radiation therapy.

Discusses management issues related to the treatment of ovarian cancer, with a focus on the utilisation of bevacizumab. Summarises applicable clinical trials, potential benefits, and reported adverse events. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

Background:Epithelioid trophoblastic tumor (ETT) is a recently described subtype of gestational trophoblastic neoplasia (GTN). Its diagnosis requires a high level of suspicion because it is often mistaken for more common cervical or uterine corpus epithelial neoplasms.Case:This is a 39-year-old woman who presented with a cervical mass and positive human chorionic gonadotropin and was diagnosed with both locally advanced squamous cell cervical carcinoma and nonmetastatic GTN. She was treated unsuccessfully with concurrent intravenous cisplatin plus pelvic radiation and single-agent intravenous methotrexate. A retrospective review of the cervical biopsy using immunohistochemistry as well as genotyping of the tumor changed the original diagnosis to ETT. It is known that ETT is relatively unresponsive to chemotherapy compared with most other types of GTN; therefore, surgery would have been the optimal treatment. She died despite multiple salvage chemotherapies.Conclusions:Malignant GTN is one of the most curable gynecologic malignancies; however, its correct diagnosis is critical for the appropriate treatment. It can be easily misdiagnosed as a carcinoma because of their morphologic similarity. Genetic fingerprinting and immunohistochemistry are potentially valuable tools to confirm the diagnosis of ETT.

Introduction/BackgroundThe GOG 240 trial established bevacizumab plus chemotherapy as standard first-line therapy for metastatic (stage IVB), persistent or recurrent cervical cancer (R/M CC). The investigator-initiated open-label randomised phase 3 BEATcc trial (NCT03556839) evaluated atezolizumab (anti-PD-L1) combined with this standard regimen, irrespective of PD-L1 status.MethodologyPatients with previously untreated measurable R/M CC not amenable to curative surgery/radiation were randomised 1:1 to standard therapy (cisplatin 50 mg/m2 or carboplatin AUC5, paclitaxel 175 mg/m2 and bevacizumab 15 mg/kg) with or without atezolizumab (1200 mg day 1 every 3 weeks). Cycles were repeated until disease progression or unacceptable toxicity. Stratification factors were prior concomitant chemoradiation (yes/no), histology (squamous cell carcinoma/adenocarcinoma) and platinum agent (cisplatin/carboplatin). Dual primary endpoints were investigator-assessed progression-free survival (PFS) per RECIST v1.1 and overall survival (OS) in the intent-to-treat population. Secondary endpoints included objective response rate (ORR), duration of response (DoR), time to first subsequent therapy (TFST), PFS2 and safety.ResultsBetween October 2018 and August 2021, 410 patients were randomised. At the data cut-off (median follow-up 32.9 months), median treatment duration was 12.7 vs 8.5 months in the atezolizumab vs standard arms, respectively; treatment was ongoing in 23% vs 7%, respectively. Both PFS and interim OS were statistically significantly improved with the addition of atezolizumab to bevacizumab and chemotherapy; secondary endpoints showed consistent results (figure 1), with ORRs of 84% (95% CI 79–89%) with atezolizumab vs 72% (95% CI 66–78%) with standard therapy. Grade ≥3 adverse events (any cause) occurred in 79% vs 75% of the atezolizumab and standard arms, respectively. Safety profiles were as expected with atezolizumab, bevacizumab and platinum-based chemotherapy.Abstract 427 Figure 1ConclusionCombining atezolizumab with first-line bevacizumab added to chemotherapy for R/M CC significantly improved all efficacy outcomes. Atezolizumab combined with bevacizumab and platinum-based chemotherapy should be considered a new first-line treatment option for patients with R/M CC.DisclosuresStudy drug and funding for this investigator-initiated study are provided by F. Hoffmann-La Roche.AO reports honoraria/consultation fees from Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, Exelisis, EMD Serono, F. Hoffmann-La Roche, Genmab, GSK, ImmunoGen, iTeos Therapeutics, MSD de España, Mersana Therapeutics, Novocure, OncXerna Therapeutics, PharmaMar, Regeneron, Shattuck Labs, Seagen and Sutro Biopharma; travel/accommodation from AstraZeneca, PharmaMar and Roche. Coauthor disclosures are provided separately.

BackgroundInvasive cervical carcinoma is associated with a human immunodeficiency virus (HIV) prevalence of >0.1%, and screening is recommended and cost-effective for cancer populations exceeding this threshold. HIV status is also prognostic for cancer-specific survival, but compliance with HIV screening is poor in the USA and abroad.ObjectivesThis study aims to describe HIV screening practices in a US comprehensive cancer center. To guide quality improvement, we identify characteristics which may predict compliance with screening.Study designWomen treated for invasive cervical cancer from January 2007 to December 2017 were identified by local cancer registry and billing data. We assessed age, race, ethnicity, insurance status, histology, stage, pregnancy, drug use, and HIV testing status. Univariate logistical regression was performed to assess predictors of completed HIV screening.ResultsOf 492 eligible women, the cumulative screening rate was 7.6%. Race, ethnicity, histology, and funding source were not predictive of screening. Every 5 year increase in age was associated with a lower chance of screening (OR 0.86, p=0.015), as was earlier stage at diagnosis (OR 0.43, p=0.017). Pregnancy during, or antecedent to, invasive cervical cancer diagnosis was significantly more predictive of screening compliance (OR 10.57, p=0.0007). Only 8/492 (1.6%) women in the cohort were active or former drug users, but within this group HIV screening was performed more frequently (OR 22.7, p<0.0001).ConclusionDespite US and international recommendations for HIV screening in AIDS-defining cancers, compliance remains low. In our centers, factors including earlier age, advanced stage, active pregnancy at diagnosis, and any drug use history were predictive of greater compliance with screening. These data will inform a tailored intervention to improve compliance with HIV screening in our population.

Homologous recombination deficiency is a critical biologic feature of ovarian cancer. This weakness in DNA damage repair relies on functional poly(ADP-ribose) polymerase. Niraparib is a poly(ADP-ribose) polymerase inhibitor, orally available and initially approved for maintenance therapy in women with ovarian cancer by the US FDA in 2017 and by the EMA in 2017 for the same indication. Ovarian cancer represents the most lethal of gynecologic malignancies. The efficacy of niraparib has changed the landscape of ovarian cancer treatment, but overall survival data is still to come. This review summarizes the data regarding niraparib mechanism of action, toxicities, single agent efficacy and novel combinations in ovarian cancer.

ObjectiveTo investigate the impact of enhancer of zeste homolog 2 (EZH2) expression on endometrial cancer cell line behavior.Materials and MethodsEnhancer of zeste homolog 2 expression levels were compared between the nonmalignant endometrial cell line T-HESC and 3 endometrial cancer cell lines, ECC-1, RL95-2, and HEC1-A. Stable EZH2 knockdown cell lines were created, and the impact on cellular proliferation, migration, and invasion were determined. Fluorescent activated cell sorting was used to examine effects of EZH2 silencing on cell cycle progression. Enhancer of zeste homolog 2 expression in endometrial cancer tissue specimens was examined using immunohistochemistry. Comparison of differences between control and short-hairpin EZH2 cell lines was performed using the Student t test and the Fischer exact test.ResultsEnhancer of zeste homolog 2 protein expression was increased in all 3 cancer cell lines and human endometrial cancer tissue specimens relative to control. RNA interference of EZH2 expression in ECC-1, RL95-2, and HEC1-A significantly decreased cell proliferation, migration, and invasion. Down-regulation of EZH2 expression resulted in a significant increase in the proportion of cells arrested in the G2/M phase. RNA interference of EZH2 expression was associated with an increase in the expression of Wnt pathway inhibitors sFRP1 and DKK3 and a concomitant decrease in β-catenin. Enhancer of zeste homolog 2 expression in human tissue samples was significantly associated with increased stage, grade, depth of invasion, and nodal metastasis.ConclusionsEnhancer of zeste homolog 2 expression is associated with tumor cell proliferation, migration, and invasion in 3 endometrial cancer cell lines as well as with increased stage, grade, depth of invasion, and nodal metastasis in human cancer tissue specimens. Further investigation into this potential therapeutic target is warranted.

Introduction/BackgroundEffective and well-tolerated treatments for PROC remain an unmet medical need; standard of care single agent chemotherapy has limited efficacy, with response rates at ~12%. Upifitamab rilsodotin (UpRi) is a Dolaflexin, high Drug-to-Antibody Ratio ADC targeting NaPi2b, a sodium-dependent phosphate transporter broadly expressed in high-grade serous epithelial ovarian cancer, with limited expression in normal tissues. UPLIFT was a single-arm Ph2 trial evaluating the efficacy and safety of UpRi in PROC.MethodologyUPLIFT enrolled patients with up to 4 prior lines of therapy; patients were dosed at 36mg/m2 Q4W. Patients enrolled regardless of NaPi2b expression; baseline tumor samples were collected to determine NaPi2b expression retrospectively. Primary endpoint was confirmed ORR in the NaPi2b-positive population. Secondary endpoints included ORR in the overall population, duration of response (DOR), and safety.Results268 patients were enrolled, 141 (53%) were determined to be NaPi2b-positive [TPS≥75]. The median prior lines of therapy among all patients was three; 31% received four prior lines of systemic treatment, 53% received at least one prior treatment for PROC. Additionally, 84% of patients received prior bevacizumab, 69% received prior PARPi. Based on data cut (May 31, 2023) investigator assessed confirmed ORR in the NaPi2b-positive population was 15.6% (95% CI, 10, 22.7); median DOR 7.4 months (95% CI, 4.2, NR). In the overall patient population, ORR was 13.1% (95% CI, 9.3, 17.7), DOR 7.4 months (95% CI, 3.6, 10.4). Dose reductions and discontinuations due to TRAE were 25% and 18.7%, respectively. The most frequently reported TRAEs were AST increase (69%), nausea (51.9%), thrombocytopenia/platelet count decrease (49.6%), fatigue (44%), anemia (39.2%) and pyrexia (37.7%). ILD/pneumonitis reported in 9.7% (Gr3 0.7%). Serious treatment emergent bleeding events were observed, including five G5 events.ConclusionIn this single-arm open label trial, ORR in the NaPi2b-positive and overall population did not show meaningful improvement compared to historical single-agent chemotherapy, though durable responses were observed.DisclosuresThis trial was sponsored by Mersana Therapeutics, Inc.