Phase 1 trial of nelfinavir added to standard cisplatin chemotherapy with concurrent pelvic radiation for locally advanced cervical cancer.

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.

A 20-year latency between hysterectomy for endometrial adenocarcinoma and solitary pulmonary metastasis: a case report.

We present a rare case pulmonary metastasis of an early stage endometrial cancer nearly 20 years after curative surgical resection. Our patient had a remote history of hysterectomy for endometrial cancer in 1998 and later had Stage 1B right upper lobe lung cancer treated with lobectomy and adjuvant chemotherapy in 2014. She was found to have an enlarging nodule in the left upper lobe in 2018, which was thought to be another primary lung cancer. She underwent left upper lobe segmentectomy for an intraoperative diagnosis of adenocarcinoma by diagnostic wedge resection of the lung nodule. Final pathologic examination of the resected tumor demonstrated an endometrial adenocarcinoma. It is important for thoracic surgeons to remain vigilant, keeping secondary lung cancer in the differential diagnosis for patients with complex oncologic histories.

Myoepithelial carcinoma or epithelioid sarcoma - A rare diagnosis with poor prognosis. A case report and review of literature.

INTRODUCTION: Myoepithelial carcinoma and proximal-type epithelioid sarcoma of the vulva are two rare malignancies with known aggressive behavior. In addition to a similar clinical course, these two disease entities also have significant histologic and pathologic overlap. Given the rarity of these malignancies, there is limited literature on the appropriate treatment regimen. Nevertheless, there is a consensus that early surgical resection is beneficial in both cases. PRESENTATION: We present a case of a patient who was initially diagnosed with myoepithelial carcinoma of the vulva with a differential later expanded to include possible epithelioid sarcoma. DISCUSSION: We demonstrate the importance in early identification of a SMARCB1 deficiency. Additionally, we suggest an appropriate treatment regimen for these patients going forward. Specifically, we encourage consideration of bilateral superficial and deep inguinal lymphadenectomies. Furthermore, sarcoma based chemotherapy regimens in the appropriate clinical setting may be beneficial in treating SMARCB1 deficient tumors. Additionally, there are now clinical trials involving EZH2 Inhibitors which may offer benefit for similar patients going forward. CONCLUSION: This case highlights the difficulty in making a definitive diagnosis, and the importance in identifying a SMARCB1 deficiency as it will affect treatment options and may allow for enrollment in ongoing clinical trials.