IL2 Targeted to CD8+ T Cells Promotes Robust Effector T-cell Responses and Potent Antitumor Immunity.

IL2 signals pleiotropically on diverse cell types, some of which contribute to therapeutic activity against tumors, whereas others drive undesired activity, such as immunosuppression or toxicity. We explored the theory that targeting of IL2 to CD8+ T cells, which are key antitumor effectors, could enhance its therapeutic index. To this aim, we developed AB248, a CD8 cis-targeted IL2 that demonstrates over 500-fold preference for CD8+ T cells over natural killer and regulatory T cells (Tregs), which may contribute to toxicity and immunosuppression, respectively.

CD8 cis-targeted IL-2 drives potent antiviral activity against hepatitis B virus.

CD8 T cells are key antiviral effectors against hepatitis B virus (HBV), yet their number and function can be compromised in chronic infections. Preclinical HBV models displaying CD8 T cell dysfunction showed that interleukin-2 (IL-2)-based treatment, unlike programmed cell death ligand 1 (PD-L1) checkpoint blockade, could reverse this defect, suggesting its therapeutic potential against HBV. However, IL-2's effectiveness is hindered by its pleiotropic nature, because its receptor is found on various immune cells, including regulatory T (T) cells and natural killer (NK) cells, which can counteract antiviral responses or contribute to toxicity, respectively.

Molecular and Clinicopathologic Characterization of Mismatch Repair-Deficient Endometrial Carcinoma Not Related to MLH1 Promoter Hypermethylation.

Universal tumor screening in endometrial carcinoma (EC) is increasingly adopted to identify individuals at risk of Lynch syndrome (LS). These cases involve mismatch repair-deficient (MMRd) EC without MLH1 promoter hypermethylation (PHM). LS is confirmed through the identification of germline MMR pathogenic variants (PV).

Functional recovery of wrist surgery with regional versus general anesthesia: a prospective observational study.

Purpose: Regional anesthesia may favour postoperative rehabilitation by inhibiting peripheral sensitization and secondary hyperalgesia. The literature on this subject is limited. In the present FUNCTION study, we sought to compare the functional recovery post orthopedic wrist surgery with regional versus general anesthesia.

Gynecological Cancer Survivors' Experiences of Dyspareunia and Factors Influencing Care-Seeking Behavior: A Qualitative Study.

Pain during sexual intercourse, also called dyspareunia, affects most women after treatment for gynecological cancer. Previous work adopted a biomedical approach to depict dyspareunia in this population, which provided a narrow perspective of this condition. Taking into account women's experiences of dyspareunia and the factors influencing their care-seeking behaviors would provide insight to improve care in the context of gynecological cancer.

Functional recovery with peripheral nerve block versus general anesthesia for upper limb surgery: a systematic review.

Background: Peripheral nerve block is a common anesthetic technique used during orthopedic upper limb surgery. Injection of local anesthetics around the target nerve inhibits the action of voltage-dependent sodium channels, inhibiting neurotransmission of pain impulses and providing motor immobility. Compared to general anesthesia, it could improve functional recovery by inhibiting nociceptive impulses and inflammation, thus reducing postoperative pain and immobilization and improving postoperative rehabilitation.

Acceptability of multimodal pelvic floor physical therapy to treat dyspareunia after gynecological malignancies: a qualitative study of women's views and experiences.

Introduction And Hypothesis: Multimodal pelvic floor physical therapy (PFPT) is recommended after gynecological malignancies to treat dyspareunia. However, data to strongly support its implementation in the cancer care continuum are lacking. The aim of this study was to explore the views and experiences of gynecological cancer survivors with dyspareunia regarding the acceptability of multimodal PFPT.

A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45).

Purpose: ATHENA (ClinicalTrials.gov identifier: NCT03522246) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without or (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA-MONO comparison of rucaparib versus placebo.

Changes in pelvic floor morphometry and muscle function after multimodal physiotherapy for gynaecological cancer survivors suffering from dyspareunia: a prospective interventional study.

Objective: To investigate the changes in pelvic floor morphometry and muscle function after multimodal pelvic floor physiotherapy treatment in gynaecological cancer survivors suffering from painful intercourse (dyspareunia).

Design: Prospective interventional study.

Setting: Three university hospitals.

Improvements following multimodal pelvic floor physical therapy in gynecological cancer survivors suffering from pain during sexual intercourse: Results from a one-year follow-up mixed-method study.

Background: A large proportion of gynecological cancer survivors suffer from pain during sexual intercourse, also known as dyspareunia. Following a multimodal pelvic floor physical therapy (PFPT) treatment, a reduction in pain and improvement in psychosexual outcomes were found in the short term, but no study thus far has examined whether these changes are sustained over time.

Purpose: To examine the improvements in pain, sexual functioning, sexual distress, body image concerns, pain anxiety, pain catastrophizing, painful intercourse self-efficacy, depressive symptoms and pelvic floor disorder symptoms in gynecological cancer survivors with dyspareunia after PFPT, and to explore women's perceptions of treatment effects at one-year follow-up.

Radiotherapy Quality Assurance in the PORTEC-3 (TROG 08.04) Trial.

Aims: Quality assurance in radiotherapy (QART) is essential to ensure the scientific integrity of a clinical trial. This paper reports the findings of the retrospective QART assessment for all centres that participated in PORTEC-3; a randomised controlled trial that compared pelvic radiotherapy with concurrent chemoradiotherapy to the pelvis followed by adjuvant chemotherapy. The trial showed an overall survival benefit for the addition of the chemotherapy in the management of women with high-risk endometrial cancer.

Radiation Therapy Techniques and Treatment-Related Toxicity in the PORTEC-3 Trial: Comparison of 3-Dimensional Conformal Radiation Therapy Versus Intensity-Modulated Radiation Therapy.

Purpose: Radiation therapy techniques have developed from 3-dimensional conformal radiation therapy (3DCRT) to intensity modulated radiation therapy (IMRT), with better sparing of the surrounding normal tissues. The current analysis aimed to investigate whether IMRT, compared to 3DCRT, resulted in fewer adverse events (AEs) and patient-reported symptoms in the randomized PORTEC-3 trial for high-risk endometrial cancer.

Methods And Materials: Data on AEs and patient-reported quality of life (QoL) of the PORTEC-3 trial were available for analysis.

F-4FMFES and F-FDG PET/CT in Estrogen Receptor-Positive Endometrial Carcinomas: Preliminary Report.

This article reports the preliminary results of a phase II clinical trial investigating the use of the estrogen receptor (ER)-targeting PET tracer 4-fluoro-11β-methoxy-16α-F-fluoroestradiol (F-4FMFES) and F-FDG PET in endometrial cancers. In parallel, noninvasive interventions were attempted to slow progression of F-4FMFES metabolites in the intestines to reduce abdominal background uptake. In an ongoing study, 25 patients who received prior pathologic confirmation of an ER-positive endometrial cancer or endometrial intraepithelial neoplasia agreed to participate in the ongoing clinical trial.

A Prospective Single-Arm Study Evaluating the Effects of a Multimodal Physical Therapy Intervention on Psychosexual Outcomes in Women With Dyspareunia After Gynecologic Cancer.

Background: Dyspareunia affects most women after treatment for gynecologic malignancies. However, to date, evidence-based interventions remain limited and no study has examined the effects of multimodal physical therapy on psychosexual outcomes in these patients.

Aim: To assess the effects of multimodal physical therapy on psychosexual outcomes including sexual distress, body image concerns, pain anxiety, pain catastrophizing, pain self-efficacy and depressive symptoms in women with dyspareunia after treatment for gynecologic malignancies.

Prevalence and Prognosis of Lynch Syndrome and Sporadic Mismatch Repair Deficiency in Endometrial Cancer.

Background: Standard screening of endometrial cancer (EC) for Lynch syndrome (LS) is gaining traction; however, the prognostic impact of an underlying hereditary etiology is unknown. We established the prevalence, prognosis, and subsequent primary cancer incidence of patients with LS-associated EC in relation to sporadic mismatch repair deficient (MMRd)-EC in the large combined Post Operative Radiation Therapy in Endometrial Carcinoma-1, -2, and -3 trial cohort.

Methods: After MMR-immunohistochemistry, MLH1-promoter methylation testing, and next-generation sequencing, tumors were classified into 3 groups according to the molecular cause of their MMRd-EC.

Characterizing Pelvic Floor Muscle Function and Morphometry in Survivors of Gynecological Cancer Who Have Dyspareunia: A Comparative Cross-Sectional Study.

Objective: More than one-half of gynecological cancer survivors are affected by pain during sexual intercourse, also known as dyspareunia. Oncological treatments may result in pelvic floor muscle (PFM) alterations, which are suspected to play a key role in dyspareunia. However, to our knowledge, no study has investigated PFM function and morphometry in this population.

Long-Term Toxicity and Health-Related Quality of Life After Adjuvant Chemoradiation Therapy or Radiation Therapy Alone for High-Risk Endometrial Cancer in the Randomized PORTEC-3 Trial.

Purpose: The survival results of the PORTEC-3 trial showed a significant improvement in both overall and failure-free survival with chemoradiation therapy versus pelvic radiation therapy alone. The present analysis was performed to compare long-term adverse events (AE) and health-related quality of life (HRQOL).

Methods And Materials: In the study, 660 women with high-risk endometrial cancer were randomly assigned to receive chemoradiation therapy (2 concurrent cycles of cisplatin followed by 4 cycles of carboplatin/paclitaxel) or radiation therapy alone.

Feasibility, acceptability and effects of multimodal pelvic floor physical therapy for gynecological cancer survivors suffering from painful sexual intercourse: A multicenter prospective interventional study.

Objectives: Painful sexual intercourse (dyspareunia) is a distressing condition affecting a large proportion of gynecological cancer survivors, yet treatments remain limited and poorly studied. This multicenter prospective interventional study examined the feasibility, acceptability and effects of multimodal pelvic floor physical therapy in gynecological cancer survivors with dyspareunia.

Methods: Thirty-one endometrial and cervical cancer survivors with dyspareunia participated in 12 weekly 60-min physical therapy sessions combining education, manual therapy, pelvic floor muscle exercises using biofeedback and home exercises, which included the use of a dilator.

Long-term safety in patients with recurrent ovarian cancer treated with niraparib versus placebo: Results from the phase III ENGOT-OV16/NOVA trial.

Objective: Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved for use in heavily pretreated patients and as maintenance treatment in patients with newly-diagnosed or recurrent ovarian cancer following a response to platinum-based chemotherapy. We present long-term safety data for niraparib from the ENGOT-OV16/NOVA trial.

Methods: This multicenter, double-blind, randomized, controlled phase III trial evaluated the efficacy and safety of niraparib for the treatment of recurrent ovarian cancer.

Molecular Classification of the PORTEC-3 Trial for High-Risk Endometrial Cancer: Impact on Prognosis and Benefit From Adjuvant Therapy.

Purpose: The randomized Adjuvant Chemoradiotherapy Versus Radiotherapy Alone in Women With High-Risk Endometrial Cancer (PORTEC-3) trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy (CTRT) versus radiotherapy alone (RT) for women with high-risk endometrial cancer (EC). Because The Cancer Genome Atlas defined an EC molecular classification with strong prognostic value, we investigated prognosis and impact of chemotherapy for each molecular subgroup using tissue samples from PORTEC-3 trial participants.

Methods: Paraffin-embedded tissues of 423 consenting patients were collected.

Functional recovery with peripheral nerve block versus general anesthesia for upper limb surgery: a systematic review protocol.

Background: Peripheral nerve block is a single injection that inhibits the transmission of peripheral nerve impulses to the central nervous system. The inhibition of the nociceptive impulse may decrease the occurrence of muscle spasm following mobilization postoperatively. This mechanism may contribute to a better functional recovery following upper limb surgery.

Niraparib Maintenance Treatment Improves Time Without Symptoms or Toxicity (TWiST) Versus Routine Surveillance in Recurrent Ovarian Cancer: A TWiST Analysis of the ENGOT-OV16/NOVA Trial.

Purpose: This study estimated time without symptoms or toxicity (TWiST) with niraparib compared with routine surveillance (RS) in the maintenance treatment of patients with recurrent ovarian cancer.

Patients And Methods: Mean progression-free survival (PFS) was estimated for niraparib and RS by fitting parametric survival distributions to Kaplan-Meier data for 553 patients with recurrent ovarian cancer who were enrolled in the phase III ENGOT-OV16/NOVA trial. Patients were categorized according to the presence or absence of a germline mutation-gmut and non-gmut cohorts.

Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial.

Background: The PORTEC-3 trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy versus pelvic radiotherapy alone for women with high-risk endometrial cancer. We updated the analysis to investigate patterns of recurrence and did a post-hoc survival analysis.

Methods: In the multicentre randomised phase 3 PORTEC-3 trial, women with high-risk endometrial cancer were eligible if they had International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage I, endometrioid grade 3 cancer with deep myometrial invasion or lymphovascular space invasion, or both; stage II or III disease; or stage I-III disease with serous or clear cell histology; were aged 18 years and older; and had a WHO performance status of 0-2.

Ascites from ovarian cancer patients stimulates MUC16 mucin expression and secretion in human peritoneal mesothelial cells through an Akt-dependent pathway.

Background: CA125 is a well-established ovarian cancer (OC) serum biomarker. The CA125 heavily glycosylated epitope is carried by the MUC16 mucin, a high molecular weight transmembrane mucin. Upon proteolytic cleavage, the extracellular domain of MUC16 is released from the cell surface into malignant ascites and blood vessels.

Serum CA125 and ascites leptin level ratio predicts baseline clinical resistance to first-line platinum-based treatment and poor prognosis in patients with high grade serous ovarian cancer.

About 20% of patients with high grade serous epithelial ovarian carcinoma (HGSOC) are intrinsically resistant to standard first-line platinum-based combination therapy. There is no marker yet available to identify these patients. In that context, all patients with HGSOC initially receive the same standard first-line platinum-based therapy, and those with intrinsically resistant diseases can only be identified retrospectively after they experienced early relapse to therapy.