Leptomeningeal metastasis from neuroendocrine carcinoma of the cervix: illustrative case.

BACKGROUND: Leptomeningeal carcinomatosis is a rare feature of metastasis that is characterized by thickening and increased contrast enhancement throughout the meninges of the central nervous system (CNS). Leptomeningeal disease (LMD) can occur as spread from primary CNS tumors or as a manifestation of metastasis to the CNS from primary tumor sites outside the CNS. Leptomeningeal disease is, however, rare in cervical cancer, in which metastasis occurs typically from local invasion. OBSERVATIONS: The authors discuss the case of CNS metastasis with LMD from the rare neuroendocrine carcinoma of the cervix (NECC). Cervical cancer infrequently metastasizes to the CNS, but NECC is an aggressive variant with greater metastatic potential. Many of these patients will have previously received pelvic radiation, limiting their candidacy for craniospinal radiation for LMD treatment due to field overlap. This illustrative case documents the first known case of NECC CNS metastasis accompanied by LMD treated with intrathecal chemotherapy. LESSONS: Reported is the first known case of NECC with CNS metastasis accompanied by LMD. The authors highlight the potentially critical role of intrathecal chemotherapy, in addition to radiotherapy, in treating leptomeningeal metastasis from cervical cancer.

Impact of Infections in Patients Receiving Pembrolizumab-Based Therapies for Non-Small Cell Lung Cancer.

Background: Immune checkpoint inhibitor (ICI) therapy has significantly improved outcomes across a range of malignancies. While infections are a well-known contributor to morbidity and mortality amongst patients receiving systemic chemotherapy regimens, little is known about the impact of infections on patients receiving ICI therapy. This study aims to assess incidence, risk factors, and outcomes in patients who develop infections while on pembrolizumab-based therapies for non-small cell lung cancer (NSCLC). Methods: Patients receiving pembrolizumab for stage III/IV NSCLC from 1/1/2017-8/1/2021 across seven hospitals were identified. Incidence and type of infection were characterized. Covariates including baseline demographics, treatment information, treatment toxicities, and immunosuppressive use were collected and compared between infected and non-infected patients. Outcomes included the rate of infections, all-cause hospital admissions, median number of treatment cycles, overall survival (OS), and progression free survival (PFS). Univariable and multivariable analysis with reported odds ratio (OR) and 95% confidence intervals (CI) were utilized to evaluate infection risks. OS and PFS were analyzed by Kaplan−Meier analysis and tested by log-rank test. p-value < 0.05 was considered statistically significant. Results: There were 243 NSCLC patients that met the inclusion criteria. Of these, 111 (45.7%) had one documented infection, and 36 (14.8%) had two or more. Compared to non-infected patients, infected patients had significantly more all-cause Emergency Department (ED) [37 (33.3%) vs. 26 (19.7%), p = 0.016], hospital [87 (78.4%) vs. 53 (40.1%), p < 0.001], and ICU visits [26 (23.4%) vs. 5 (3.8%), p < 0.001], and had poorer median OS (11.53 [95% CI 6.4−16.7] vs. 21.03 [95% CI: 14.7−24.2] months, p = 0.033). On multivariable analysis, anti-infective therapy (OR 3.32, [95% CI: 1.26−8.76], p = 0.015) and ECOG of >1 (OR 5.79, [95% CI 1.72−19.47], p = 0.005) at ICI initiation conferred an increased risk for infections. At last evaluation, 74 (66.7%) infected and 70 (53.0%) non-infected patients died (p = 0.041). Conclusion: Infections occurred in nearly half of patients receiving pembrolizumab-based therapies for NSCLC. Infected patients had frequent hospitalizations, treatment delays, and poorer survival. ECOG status and anti-infective use at ICI initiation conferred a higher infection risk. Infection prevention and control strategies are needed to ameliorate the risk for infections in patients receiving ICIs.

Comparative study of endometrial & subendometrial angiogenesis in unexplained infertile versus normal fertile women.

Background & objectives: Local angiogenesis in endometrium has been shown to be an essential pre-requisite for endometrial receptivity needed for implantation and gestation. Recently, numerous diagnostic gears have been projected to 'measure' or 'estimate' the endometrial receptivity relying upon angiogenic factors helping throughout implantation. This study evaluated the endometrial and subendometrial blood flow and the local endometrial gland vascular endothelial growth factor (EG-VEGF) expression as markers of local angiogenesis. Methods: The present study was done to give quantitative assessment of endometrial thickness (ET), endometrial blood flow and subendometrial blood flow colour Doppler indices with endometrial vascular zones. Endometrial biopsy was taken and with VEGF stained and scored with immunohistochemistry. Results: The mean ET for fertile women was 9.41 mm, while in unexplained infertile women it was around 7.90 mm. Upon comparison of ET with EG-VEGF which is considered as a gold standard with correlation coefficient, the present study suggested a positive correlation of EG-VEGF with ET, endometrial pulsatility index (PI), and subendometrial PI also the vascular zones were considered as significant. However, a strong negative correlation was seen with subendometrial resistivity index and PI. Interpretation & conclusions: The present study suggests that uterine ultrasound, uterine colour Doppler and EG-VEGF are parameters which can be used as markers of local angiogenesis for endometrial receptivity in the evaluation of women with unexplained infertility.

Successful treatment of a stage IIIC small-cell carcinoma of the ovary hypercalcemic subtype using multi-modality therapeutic approach.

Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but highly undifferentiated, aggressive malignancy that primarily affects young women. Due to its early onset, unclear familial history and vague presenting symptoms, most SCCOHT patients present late with advanced disease. The prognosis is extremely poor, with <10% disease-free survival for advanced stages. Although several therapeutic regimens have been proposed, to date there is no consensus on the optimal strategy. Here, we describe a successful case of advanced-stage SCCOHT of the left ovary treated with cytoreductive surgery, semi-intense chemotherapy, high-dose consolidative chemotherapy, autologous hematopoietic stem cell transplantation and pelvic radiation with long-term survival. Given the almost universal mortality of advanced SCCOHT in long-term follow-up, we believe this case highlights the importance of prompt diagnosis when a young patient presents with abdominal swelling and hypercalcemia as well as early, aggressive, combined modality treatment. This case is also especially remarkable given the patient underwent fertility preservation surgery, which is not recommended by most of the current literature. However, as therapies improve and more young patients may survive SCCOHT, the question of fertility will increase in relevance. We believe the pros and cons of conservation should be discussed in detail with the patient.