The effect of the peritoneal tumor microenvironment on invasion of peritoneal metastases of high-grade serous ovarian cancer and the impact of NEOADJUVANT chemotherapy.

Peritoneal metastases of high-grade serous ovarian cancer (HGSOC) are small-sized deposits with superficial growth toward the peritoneal cavity. It is unknown whether integrity of the peritoneal elastic lamina (PEL) correlates with the peritoneal tumor microenvironment (pTME) and whether neoadjuvant chemotherapy (NACT) affects the pTME. We explored integrity of PEL, composition of pTME, effects of NACT, and the prognostic implications in patients with extensive peritoneal metastases of HGSOC. Peritoneal samples (n = 69) were collected during cytoreductive surgery between 2003 and 2016. Clinical data were collected from medical charts. Integrity of PEL was evaluated with elastic stains. T cell (CD3, CD8) and M2-macrophage markers (CD163) were scored using algorithms created in definiens tissue studio. Patients with a disrupted PEL (n = 39; 57%), more often had residual disease after surgery (p = 0.050), compared to intact PEL. An intact PEL was associated with increased intraepithelial (ie) CD8+ cells (p = 0.032), but was not correlated with improved survival. After NACT, increased ieCD3+ cells were shown, compared to no-NACT (p = 0.044). Abundance of total CD3+ and CD8+ cells were associated with PFS (multivariate HR 0.40; 95%CI 0.23-0.69 and HR 0.49; 95%CI 0.29-0.83) and OS (HR 0.33; 95%CI 0.18-0.62 and HR 0.36; 95%CI 0.20-0.64). M2-macrophage infiltration was not correlated with survival. NACT increases abundance of ieCD3+ cells in peritoneal metastases of HGSOC. Increase of CD3+ and CD8+ cells is associated with improved PFS and OS. This suggests that CD3+ and CD8+ cells may function as prognostic biomarkers. Their role as predictive biomarker for chemotherapy or immunotherapy response in HGSOC warrants further research.

The effect of adjuvant chemotherapy on survival in patients with FIGO stage I high-grade serous ovarian cancer.

OBJECTIVE: The benefit of adjuvant chemotherapy for FIGO stage I, high-grade serous ovarian cancer (HGSOC) after optimal staging is a matter of debate. We investigated the effect of adjuvant chemotherapy on recurrence-free survival (RFS) and overall survival (OS) in a population-based cohort study. METHODS: All patients diagnosed in the Netherlands between 2002 and 2014 with FIGO stage I HGSOC who underwent surgical staging were included. Data on clinical characteristics, histopathology, completeness of staging and survival were collected from the Netherlands Cancer Registry and Dutch Pathology Registry. Recurrence data was collected from hospital files. We used Kaplan-Meier methods to estimate RFS and OS and Cox-proportional hazard analyses to control for differences in baseline characteristics between patients who did or did not receive chemotherapy. RESULTS: We identified 223 patients who underwent optimal staging procedures including lymph node sampling. Events of disease recurrence occurred in 21 of the 101 patients (21%) who received adjuvant chemotherapy and in 46 of the 122 patients (38%) who did not (multivariable hazard ratio (HR), 0.37; 95%CI 0.22-0.64; p < 0.01). Five-year RFS was 81% after staging plus chemotherapy and 59% after staging only. At a median follow-up of 105 months, 21 patients (21%) in the chemotherapy group and 38 patients (31%) in the no-chemotherapy group had died (multivariable HR 0.50; 95%CI 0.28-0.89; p = 0.02). Ten-year OS was 78% with chemotherapy and 62% without chemotherapy. CONCLUSIONS: Adjuvant chemotherapy improves long-term RFS and OS in patients with FIGO stage I HGSOC after optimal staging.

The histophysiology and pathophysiology of the peritoneum.

The peritoneum is an extensive serous organ with both epithelial and mesenchymal features and a variety of functions. Diseases such as inflammatory peritonitis and peritoneal carcinomatosis can induce disturbance of the complex physiological functions. To understand the peritoneal response in disease, normal embryonic development, anatomy in healthy conditions and physiology of the peritoneum have to be understood. This review aims to summarize and discuss the literature on these basic peritoneal characteristics. The peritoneum is a dynamic organ capable of adapting its structure and functions to various physiological and pathological conditions. It is a key element in regulation of inflammatory responses, exchange of peritoneal fluid and prevention of fibrosis in the abdominal cavity. Disturbance of these mechanisms may lead to serious conditions such as the production of large amounts of ascites, the generation of fibrotic adhesions, inflammatory peritonitis and peritoneal carcinomatosis. The difficulty to treat diseases, such as inflammatory peritonitis and peritoneal carcinomatosis, stresses the necessity for new therapeutic strategies. This review provides a detailed background on the peritoneal anatomy, microenvironment and immunologic responses which is essential to generate new hypotheses for future research.