Use of direct oral anticoagulants for postoperative venous thromboembolism prophylaxis after surgery for gynecologic malignancies

Venous thromboembolism is a preventable cause of postoperative mortality in patients undergoing surgery for malignancy. Current standard of care based on international guideline recommends 28 days of extended thromboprophylaxis after major abdominal and pelvic surgery for malignancies with unfractionated heparin or low molecular weight heparin. Direct oral anticoagulants have been approved for the treatment of venous thromboembolism in the general population. This regimen has a significant advantage over other types of anticoagulation regimens, particularly being administered by non-parenteral routes and without the need for laboratory monitoring. In this review, we evaluate the role of direct anticoagulation and provide an update on completed and ongoing clinical trials.

Primary Bartholin Adenocarcinoma: a Rare Case and Radiotherapy as Definitive Treatment

Primary vulvar adenocarcinoma is a very rare neoplasm, accounting for only 1% of all gynecologic malignancies. Most of the glandular carcinomas originated from the Bartholin’s gland. Because of the rare incidence, the pathogenesis and radiotherapy response are not fully understood. A 47-year-old female from our hospital was diagnosed with primary Bartholin adenocarcinoma and received radiotherapy as definitive treatment. We evaluated the presence of high-risk and low-risk human papillomavirus (HPV) DNA to associate the role of HPV infection, and evaluated its molecular features by the expression of vimentin, p16, estrogen receptor, progesterone receptor, S-100, and Ki 67.

Understanding the Role and Clinical Applications of Exosomes in Gynecologic Malignancies: A Review of the Current Literature

Background: Gynecologic malignancies are those which arise in the female reproductive organs of the ovaries, cervix, and uterus. They carry a great deal of morbidity and mortality for patients, largely due to challenges in diagnosis and treatment of these cancers. Although advances in technology and understanding of these diseases have greatly improved diagnosis, treatment, and ultimately survival for patients with gynecologic malignancies over the last few decades, there is still room for improvements in diagnosis and treatment, for which exosomes may be the key. This paper reviews the current knowledge regarding gynecologic tumor derived-exosomal genetic material and proteins, their role in cancer progression, and their potential for advancing the clinical care of patients with gynecologic cancers through novel diagnostics and therapeutics. Literature Review: Ovarian tumor derived exosome specific proteins are reviewed in detail, discussing their role in ovarian cancer metastasis. The key microRNAs in cervical cancer and their implications in future clinical use are discussed. Additionally, uterine cancer-associated fibroblast (CAF)-derived exosomes which may promote endometrial cancer cell migration and invasion through a specific miR-148b are reviewed. The various laboratory techniques and commercial kits for the isolation of exosomes to allow for their clinical utilization are described as well. Conclusion: Exosomes may be the key to solving many unanswered questions, and closing the gaps so as to improve the outcomes of patients with gynecologic cancers around the world. The potential utilization of the current knowledge of exosomes, as they relate to gynecologic cancers, to advance the field and bridge the gaps in diagnostics and therapeutics highlight the promising future of exosomes in gynecologic malignancies.

Clinical implementation and initial experience with a 1.5 Tesla MR-linac for MR-guided radiotherapy for gynecologic cancer: An R-IDEAL stage 1/2a first in humans/feasibility study of new technology implementation

Purpose: Magnetic resonance imaging-guided linear accelerator systems (MR-linacs) can facilitate the daily adaptation of radiotherapy plans. Here, we report our early clinical experience using an MR-linac for adaptive radiotherapy of gynecologic malignancies. Methods and Materials: Treatments were planned with an Elekta Monaco v5.4.01 and delivered by a 1.5 Tesla Elekta Unity MR-linac. The system offers a choice of daily adaptation based on either position (ATP) or shape (ATS) of the tumor and surrounding normal structures. The ATS approach has the option of manually editing the contours of tumors and surrounding normal structures before the plan is adapted. Here we documented the duration of each treatment fraction; set-up variability (assessed by isocenter shifts in each plan) between fractions; and, for quality assurance, calculated the percentage of plans meeting the ;γ-criterion of 3%/3-mm distance to agreement. Deformable accumulated dose calculations were used to compare ATP plans with reference dose plans. Results: Of the 10 patients treated with 90 fractions on the MR-linac, most received boost doses to recurrence in nodes or isolated tumors. Each treatment fraction lasted a median 32 minutes; fractions were shorter with ATP than with ATS (30 min vs 42 min, P<0.0001). The γ-criterion for all fraction plans exceeded >90% (median 99.9%, range 92.4%-100%), i.e., all plans passed quality assurance testing. The average extent of isocenter shift was <0.5 cm in each axis. The accumulated dose to the gross tumor volume was within 10% of the reference plan for all ATP cases. Accumulated doses for lesions in the pelvic periphery were within 1% of the reference plan as opposed to -5.8% to -9.6% for central tumors. Conclusions: The MR-linac is a reliable and clinically feasible tool for treating patients with gynecologic cancer.

Stereotactic radiosurgery for brain metastases from pelvic gynecological malignancies: oncologic outcomes, validation of prognostic scores, and dosimetric evaluation

IntroductionStereotactic radiosurgery is a well-established treatment option in the management of brain metastases. Multiple prognostic scores for prediction of survival following radiotherapy exist, but are not disease-specific or validated for radiosurgery in women with primary pelvic gynecologic malignancies metastatic to the brain. The aim of the present study is to evaluate the feasibility, safety, outcomes, and impact of established prognostic scores.MethodsWe retrospectively identified 52 patients treated with radiotherapy for brain metastases between 2008 and 2021. Stereotactic radiosurgery was utilized in 31 patients for an overall number of 75 lesions; the remaining 21 patients received whole-brain radiotherapy. Kaplan-Meier survival analysis and the log-rank test were used to calculate and compare survival curves and univariate and multivariate Cox regression to assess the influence of cofactors on recurrence, local control, and prognosis.ResultsWith a median follow-up of 10.7 months, overall survival rates post radiosurgery were 65.3%, 51.3%, and 27.7% for 1, 2, and 5 years, respectively, which were significantly higher than post whole-brain radiotherapy (p=0.049). Five local failures (6.7%) were detected, resulting in 1 and 2 year local cerebral control rates of 97.4% and 94.0%, respectively. Univariate factors for prediction of superior overall survival were high performance status (p=0.030) and application of three prognostic scores, especially the Recursive Partitioning Analysis score (p=0.028). Uni- and multivariate analysis revealed that extracranial progression prior to radiosurgery was significant for inferior overall survival (p<0.0001). Radionecrosis was diagnosed in five women (16%); long-term neurotoxicity was significantly worse after whole-brain radiotherapy compared with radiosurgery (p=0.023).ConclusionStereotactic radiosurgery for brain metastases from pelvic gynecologic malignancies appears to be safe and well tolerated, achieving promising local cerebral control. Prognostic scores were shown to be transferable and radiosurgery should be recommended as primary intracranial treatment, especially in women with no prior extracranial progression and Recursive Partitioning Analysis class I.