Faculty Bibliography

BACKGROUND:Nelfinavir (NFV), an HIV-1 protease inhibitor, has been shown to sensitize cancer cells to chemoradiation (CRT). The objectives of this phase 1 trial were to evaluate safety and identify the recommended phase 2 dose of NFV added to concurrent CRT for locally advanced cervical cancer. METHODS:Two dose levels of NFV were evaluated: 875 mg orally twice daily (dose level 1 [DL1]) and 1250 mg twice daily (DL2). NFV was initiated 7 days before CRT and continued through CRT completion. Toxicity, radiographic responses, and pathologic responses were evaluated. Serial tumor biopsies (baseline, after NFV monotherapy, on NFV + CRT, and posttreatment) were evaluated by immunohistochemistry, NanoString, and reverse-phase-protein-array analyses. RESULTS:NFV sensitized cervical cancer cells to radiation, increasing apoptosis and tumor suppression in vivo. Patients (n = 13) with International Federation of Gynecology and Obstetrics stage IIA through IVA squamous cell cervical carcinoma were enrolled, including 7 patients at DL1 and 6 patients at DL2. At DL1, expansion to 6 patients was required after a patient developed a dose-limiting toxicity, whereas no dose-limiting toxicities occurred at DL2. Therefore, DL2 was established as the recommended phase 2 dose. All patients at DL2 completed CRT, and 1 of 6 experienced grade 3 or 4 anemia, nausea, and diarrhea. One recurrence was noted at DL2, with disease outside the radiation field. Ten of 11 evaluable patients remained without evidence of disease at a median follow-up of 50 months. NFV significantly decreased phosphorylated Akt levels in tumors. Cell cycle and cancer pathways also were reduced by NFV and CRT. CONCLUSIONS:NFV with CRT is well tolerated. The response rate is promising compared with historic controls in this patient population and warrants further investigation.

This publication represents an extensive literature review with the goal of providing guidelines for the evaluation and management of cervical adenocarcinoma in situ (AIS). The authors drafted the guidelines on behalf of the Society of Gynecologic Oncology, and the guidelines have been reviewed and endorsed by the ASCCP. These guidelines harmonize with the ASCCP Risk-Based Management Consensus Guidelines and provide more specific guidance beyond that provided by the ASCCP guidelines. Examples of updates include recommendations to optimize the diagnostic excisional specimen, AIS management in the setting of positive compared with negative margins on the excisional specimen, surveillance and definitive management after fertility-sparing treatment, and management of AIS in pregnancy. The increasing incidence of AIS, its association with human papillomavirus-18 infection, challenges in diagnosis owing to frequent origin within the endocervical canal, and the possibility of skip lesions all make AIS a unique diagnosis whose management needs to be differentiated from the management of the more prevalent squamous cell dysplasia.

INTRODUCTION/BACKGROUND:Gynecologic malignancies are estimated to affect 110,070 women and will be the cause of death in approximately 32,120 in 2018. Endometrial cancer is among the most prevalent with 63,320 estimated new cases and approximately 11,350 deaths, followed by ovarian cancer with an estimate of 22,000 new cases and 14,000 deaths annually. Obesity is one of the most modifiable risk factors. Providers should engage in a multifaceted approach to patient education and healthcare to decrease the projected cases of obesity-related cancers. BACKGROUND:The literature demonstrates a significant link between obesity and the development of certain malignancies such as endometrial, pancreatic, and renal cancer. Specific mechanisms found to play a role in the development of these malignancies include alterations of the metabolic pathway attributed to lipid accumulation as well as a chronic inflammatory process. Obesity also predisposes patients to other medical comorbidities as well as a poorer prognosis once a diagnosis of cancer is established. Factors contributing to poorer prognosis include challenges with treatment planning, specifically pertaining to inappropriate chemotherapy dosing and delivery of radiation therapy. Surgical approach and perioperative management are similarly challenging in obese patients and are associated with increased risk of complications. CONCLUSION/CONCLUSIONS:Obesity is a modifiable factor which is associated with an increased risk of cancer and poorer outcomes. Providers should educate patients on all health hazards of obesity, including increased risk of cancer, and encourage them to participate in a structured weight loss plan.

Postoperative management of patients with vulvar cancer is associated with a high incidence of poor wound healing and radiation -induced late tissue necrosis. This case series demonstrates the impact on wound healing with the use of hyperbaric oxygen therapy and advanced wound care following radical vulvectomy and/or radiation therapy. A retrospective case series was performed of all patients from 2016 to 2017 with lower genital cancer who underwent radical surgery with or without chemoradiation treatment, experienced wound dehiscence or late tissue radionecrosis, and were treated with advanced wound care, including hyperbaric oxygen therapy (HBO). Five patients were included with a mean age of 63; four had squamous cell carcinoma and one patient had vaginal adenocarcinoma secondary to prior diethylstilbestrol exposure. Three patients underwent radical vulvectomy. All received pelvic radiation therapy, subsequently experienced wound complications, and were managed with advanced wound care and HBO. The mean reduction in wound area at the final wound follow up visit after completion of HBO therapy was found to be 76%, ranging 42-95%, with an average follow up of five months. The mean number of HBO sessions per patient was 58. Complete tissue granulation or significant improvement in tissue radionecrosis was present in all patients. Advanced wound care and hyperbaric oxygen therapy are beneficial in the management of postoperative wound complications. Prospective studies are needed to identify the optimal use of perioperative hyperbaric oxygen and appropriate wound care for patients with gynecologic malignancies.