Gastric mucosa as a rare recurrence location of endometrial endometrioid adenocarcinoma.

Endometrial cancer is the most common gynecologic malignancy in the United States, with a prevalence of 25.7 per 100,000 women per year (Mahdy et al., 2023). Recurrences of endometrial carcinoma have a mean interval of occurring 2-3 years after primary treatment, with 64 % of cases occurring within 2 years and 87 % by the third year (Kurra et al., 2013). The most common sites of recurrence include the pelvis, pelvic and para-aortic lymph nodes, peritoneum, and the lungs (Kurra et al., 2013). Here, we describe a 72-year-old female with recurrent Stage IIIA endometrial adenocarcinoma in the gastric mucosa, an unusual location for recurrence of this type of cancer.

Integrating Precision Medicine into the Contemporary Management of Gynecologic Cancers.

PURPOSE OF REVIEW: The treatment of patients with advanced gynecologic malignancies remains challenging. Advancements in genomics have led to recognition and development of individualized therapeutic targets. This article reviews the current trends in precision medicine for treatment of gynecologic cancers. RECENT FINDINGS: With the identification of the molecular aberrations inherent to gynecologic malignancies, we have discovered targetable mutations. Specific to ovarian, endometrial and cervical cancers, potential therapeutic targets that have been identified and shown to have benefit include: hormonal therapies, anti-angiogenic agents, poly-ADP-ribose polymerase inhibitors (PARPi), and immunotherapy. The adoption of targeted therapeutics for the treatment of gynecologic cancers has been gradual, but we have started to see the rapid employment of novel targeted agents into clinical trial development, leading to new treatment approvals. However, there are challenges to the universal precision medicine implementation, and future studies need to identify, discover, and validate robust biomarkers with strong prognostic/predictive capabilities.

Surgical Management of Gynecologic Cancers.

This article addresses the role of surgery in the management of gynecologic cancers with liver metastases. The authors review the short-term and long-term outcomes of aggressive resection through retrospective and randomized studies. Although the data supporting aggressive resection of liver metastasis are largely retrospective and case based, the randomized control data to address neoadjuvant versus chemotherapy have been widely criticized. Residual disease remains an important predictor for survival in ovarian cancer. If a patient cannot achieve near optimal cytoreduction, radical cytoreductive procedures, such as hepatic resection, should be considered for palliation only.

Cost-effectiveness of niraparib, rucaparib, and olaparib for treatment of platinum-resistant, recurrent ovarian carcinoma.

BACKGROUND: Olaparib was approved on December 19, 2014 by the US FDA as 4th-line therapy (and beyond) for patients with germline BRCA1/2 mutations; rucaparib was approved on December 19, 2016 as 3rd-line therapy (and beyond) for germline or somatic BRCA1/2-mutated recurrent disease. On October 23, 2019, niraparib was approved for treatment of women with damaging mutations in BRCA1/2 or other homologous recombination repair genes who had been treated with three or more prior regimens. We compared the cost-effectiveness of PARPi(s) with intravenous regimens for platinum-resistant disease. METHODS: Median progression-free survival (PFS) and toxicity data from regulatory trials were incorporated in a model which transitioned patients through response, hematologic complications, non-hematologic complications, progression, and death. Using TreeAge Pro 2017, each PARPi(s) was compared separately to non­platinum-based and bevacizumab-containing regimens. Costs of IV drugs, managing toxicities, infusions, and supportive care were estimated using 2017 Medicare data. Incremental cost-effectiveness ratios (ICERs) were calculated and PFS was reported in quality adjusted life months for platinum-resistant populations. RESULTS: Non­platinum-based intravenous chemotherapy was most cost effective ($6,412/PFS-month) compared with bevacizumab-containing regimens ($12,187/PFS-month), niraparib ($18,970/PFS-month), olaparib ($16,327/PFS-month), and rucaparib ($16,637/PFS-month). ICERs for PARPi(s) were 3-3.5× times greater than intravenous non­platinum-based regimens. CONCLUSION: High costs of orally administered PARPi(s) were not mitigated or balanced by costs of infusion and managing toxicities of intravenous regimens typically associated with lower response and shorter median PFS. Balancing modest clinical benefit with costs of novel therapies remains problematic and could widen disparities among those with limited access to care.

A profile on the FoundationFocus CDxBRCA tests.

Introduction: Poly(ADP-ribose) polymerase (PARP) inhibitors, including rucaparib, are the only targeted class of therapeutics approved for recurrent epithelial ovarian carcinoma with a predictive biomarker. Currently, three different PARP inhibitors are approved for either the treatment of ovarian cancer or maintenance of remission following chemotherapy. The Foundation Focus CDxBRCA is an FDA-cleared next-generation sequencing tumor tissue assay that detects somatic and sometimes germline mutations in BRCA1 and BRCA2 genes.Areas covered: The authors discuss the evolution of the ovarian cancer genomic testing landscape relative to PARP inhibition, with a focus on Foundation Focus CDxBRCA and CDxBRCA Loss of Heterozygosity (LOH), the complementary diagnostics (CDx) to rucaparib.Expert opinion: Relatively early in PARP inhibitor development, women with somatic and/or germline mutations in the BRCA1 and BRCA2 genes were found to have higher response rates to PARP inhibitors with longer durability than women who were BRCA wildtype. Other measures of homologous recombination deficiency including LOH have proven to be predictive biomarkers also. Because PARP biomarkers are genomic and complex, co-development of high-performance companion diagnostics was a high priority. The Foundation Focus test began as a next-generation sequencing assay capable of detecting germline (gBRCA) and somatic (sBRCA) mutations that predict response to rucaparib treatment. The addition of LOH to the assay was validated by a clinical trial supporting expansion of the Rucaparib FDA label to include maintenance of chemotherapy response.

Endometrial cancer in the morbidly obese: a review.

PURPOSE OF REVIEW: With a worldwide increase in obesity, there has been an increase in obesity-related diseases. Endometrial cancer is a common cause of cancer for women worldwide. Incidence of endometrial cancer has risen worldwide. Accompanying these patients are risk factors and challenges that may prevent standard of care from being delivered. RECENT FINDINGS: The current article describes recent literature describing surgical approaches to the obese patient and special considerations in this population. This article also reviews bariatric surgery and endometrial cancer as well as new updates in radiation, chemotherapy and hormonal therapy research in the obese population. SUMMARY: The current article reviews therapeutics and surgery in the morbidly obese for the treatment of endometrial cancer.

Fertility preserving treatment for gynecologic malignancies: a review of recent literature.

PURPOSE OF REVIEW: A significant number of women diagnosed with a gynecologic malignancy meet criteria for fertility-sparing treatment. Women are continuing to delay childbearing; the importance of fertility-sparing therapy is, therefore, increasing. It is imperative that physicians understand the options for, and limitations of, these treatments. RECENT FINDINGS: Recent research has demonstrated improved outcomes for endometrial cancer by adding targeted hysteroscopic resection to progestin therapy. Cervical cancer research has focused on oncologic and pregnancy outcomes following management with radical trachelectomy, confirming its safety. Given the high rates of preterm birth following trachelectomy, studies have evaluated the adequacy of fertility counseling prior to treatment, and have looked for predictive factors for preterm birth. Additionally, research has shown a rise in the percentage of women receiving conservative treatment for both endometrial and cervical cancer. SUMMARY: With an increasing number of women seeking conservative treatment, physicians must understand the safety and implications of such therapy. Retrospective studies have demonstrated the safety of fertility-sparing treatment for both endometrial and cervical cancer; prospective research is currently underway to provide better guidance for future directions of fertility-sparing treatment for gynecologic malignancies.

Rational design for cervical cancer therapeutics: cellular and non-cellular based strategies on the horizon for recurrent, metastatic or refractory cervical cancer.

INTRODUCTION: Though cervical cytology, HPV DNA testing, and pre-invasive disease management has significantly reduced the number of new diagnoses of cervical cancer, women with persistent oncogenic HPV infection are at significant risk for developing invasive cervical cancer. Early stage and locally advanced disease can be cured, but women with advanced or recurrent disease have a very poor prognosis. This underscores the need for different treatment strategies for advanced cervical cancer, the most promising of which are novel therapeutics that target the ability of HPV to overcome host immune tolerance. Areas covered: This review includes new therapies being investigated for the treatment of recurrent, metastatic or refractory cervical cancer, separated into broad categories of cellular and non-cellular based strategies. Expert opinion: Advanced and recurrent cervical cancer has a poor prognosis, prompting investigations into the development of strategies that will eradicate tumor and/or overcome host immunologic tolerance of disease. It is unknown whether it will be these strategies alone or a combination of treatment modalities that will ultimately provide the best outcomes; nevertheless, the new data are promising.

Primary low-grade endometrial stromal sarcoma of the omentum.

•Extra-uterine endometrial stromal sarcoma may arise in endometriosis.•Abdominal exploration for extra pelvic endometriosis is warranted.•Representative endometriotic implants should be resected and/or biopsied if clinically suspicious.

US FDA oncology drug approvals in 2014.

Cancer is a close second to heart disease for cause of death in the USA, and could soon surpass heart disease as the population ages and the incidence of cancer continues to increase. While heart disease can be addressed through behavior modification and education (e.g., smoking cessation, dietary changes, exercises that promote cardiovascular fitness), pharmacology and improved surgical devices and methods, cancer ultimately requires improved and novel drug treatments to bring mortality rates down. In 2014, the US FDA approved 17 drugs and/or drug combinations in 12 disease sites for a total of 19 indications in melanoma, hematologic malignancies, gastrointestinal carcinoma, non-small-cell lung cancer, gynecologic malignancies and lymphoma/lymphoproliferative disorders.

Urticarial Vasculitis in a Teenage Girl.

This case involves a 13-year-old female who presented to the pediatrician for a routine check-up with complaints of a long history of intermittent diarrhea followed by a severe rash lasting for up to a week afterwards. The mother had described her daughter's condition to multiple physicians, several whom had seen her during flare-ups. The nonmigratory lesions resembled "hives" with a single lesion lasting for 48 to 72 hours and resolving into what her parent described as a bruise. They often diagnosed her daughter with urticaria and prescribed steroids, which did resolve the acute flare-ups. None of the physicians, however, focused on the disease's evolution and chronicity in an effort toward diagnosis and prevention. The patient was referred by her pediatrician to a dermatologist who diagnosed the patient with urticarial vasculitis. She was initially started on dapsone 25 mg and was increased over a period of months to a maintenance dose of 100 mg daily. She has had no recurrences in her cutaneous or systemic symptoms on this dose. She is closely monitored by her dermatologist on a regular basis with twice yearly complete blood counts. Several attempts have been made to discontinue the dapsone, resulting in a flare of her gastrointestinal symptoms. This patient suffered with this condition for almost 10 years. This is a reminder that spending extra time to think through a patient's problem early on may prevent years of suffering for patients and their families.