Optical coherence tomography for multicellular tumor spheroid category recognition and drug screening classification via multi-spatial-superficial-parameter and machine learning.

Optical coherence tomography (OCT) is an ideal imaging technique for noninvasive and longitudinal monitoring of multicellular tumor spheroids (MCTS). However, the internal structure features within MCTS from OCT images are still not fully utilized. In this study, we developed cross-statistical, cross-screening, and composite-hyperparameter feature processing methods in conjunction with 12 machine learning models to assess changes within the MCTS internal structure. Our results indicated that the effective features combined with supervised learning models successfully classify OVCAR-8 MCTS culturing with 5,000 and 50,000 cell numbers, MCTS with pancreatic tumor cells (Panc02-H7) culturing with the ratio of 0%, 33%, 50%, and 67% of fibroblasts, and OVCAR-4 MCTS treated by 2-methoxyestradiol, AZD1208, and R-ketorolac with concentrations of 1, 10, and 25 µM. This approach holds promise for obtaining multi-dimensional physiological and functional evaluations for using OCT and MCTS in anticancer studies.

The role and participation of immune cells in the endometrial tumor microenvironment.

The tumor microenvironment is surrounded by blood vessels and consists of malignant, non-malignant, and immune cells, as well as signalling molecules, which primarily affect the therapeutic response and curative effects of drugs in clinical studies. Tumor-infiltrating immune cells participate in tumor progression, impact anticancer therapy, and eventually lead to the development of immune tolerance. Immunotherapy is evolving as a promising therapeutic intervention to stimulate and activate the immune system to suppress cancer cell growth. Endometrial cancer (EC) is an immunogenic disease, and in recent years, immunotherapy has shown benefit in the treatment of recurrent and advanced EC. This review discusses the key molecular pathways associated with the intra-tumoral immune response and the involvement of circulatory signalling molecules. Specific immunologic signatures in EC which offer targets for immunomodulating agents, are also discussed. We have summarized the available literature in support of using immunotherapy in EC. Lastly, we have also discussed ongoing clinical trials that may offer additional promising immunotherapy options in the future. The manuscript also explored innovative approaches for screening and identifying effective drugs, and to reduce the financial burdens for the development of personalized treatment strategies. Collectively, we aim to provide a comprehensive review of the role of immune cells and the tumor microenvironment in the development, progression, and treatment of EC.

Vulvar Intraepithelial Neoplasia: A Review of the Disease and Current Management.

IMPORTANCE: Vulvar intraepithelial neoplasia (VIN) represents an increasingly common, yet challenging diagnosis that shares many common risk factors with cervical intraepithelial neoplasia. However, unlike cervical intraepithelial neoplasia, effective screening and treatment strategies are much less defined for patients with VIN. OBJECTIVE: The objective of this article is to review the underlying risk factors leading to the development of VIN, identify special populations at risk for VIN, and outline acceptable treatment strategies. EVIDENCE ACQUISITION: This literature review was performed primarily using PubMed. RESULTS: Vulvar intraepithelial neoplasia can be separated into usual VIN (uVIN) and differentiated VIN (dVIN). The more common uVIN is related to underlying human papillomavirus infection, whereas dVIN occurs in the setting of other vulvar inflammatory conditions such as lichen sclerosis. Differentiated VIN carries a higher risk of progression to invasive malignancy. Extramammary Paget disease is a rare intraepithelial adenocarcinoma unrelated to uVIN and dVIN, although management is similar. CONCLUSIONS AND RELEVANCE: Vulvar intraepithelial neoplasia is a preinvasive neoplasia of the vulva with few robust strategies for surveillance or management. Careful examination with targeted biopsy is warranted for suspicious lesions, and a combination of surgical and medical management can be tailored for individual patient needs.

Extending the platinum-free interval: The impact of omitting 2nd line platinum chemotherapy in intermediate platinum-sensitive ovarian cancer.

OBJECTIVES: Patients with epithelial ovarian cancer (EOC) recurring between 6 and 12 months after primary platinum chemotherapy have worse prognosis than those recurring in >12 months. Artificially prolonging the platinum-free interval (PFI) with cytotoxic chemotherapy was tested in MITO-8 with poor outcomes. This study aimed to determine the impact of using non-platinum or targeted therapy in 2nd line treatment of EOC patients recurring 6-12 months after completion of primary platinum-based chemotherapy. METHODS: A multi-institutional retrospective review of 177 patients with recurrent EOC and PFI of 6-12 months following primary chemotherapy was performed comparing platinum versus non-platinum chemotherapy or targeted therapy for 2nd line treatment. PFI1 was defined as the date of last chemotherapy to date of recurrence. PFS2/3 were defined as start of 2nd or 3rd line chemotherapy to start of subsequent line. RESULTS: Of 177 patients, the majority of patients were Caucasian, had serous histology, and underwent primary cytoreductive surgery. Median PFI1 was 8.2 months (95% CI 8-9 months). Second line platinum was omitted in 28% of patients. Bevacizumab was used in 2nd line in 16% of patients; 19% received other targeted therapies. Median PFS2 for platinum chemotherapy was longer than non-platinum (7.1 vs 3 months, p = 0.0114). Median PFS2 was significantly longer for platinum vs. targeted therapy (7.1 vs. 3 months p = 0.0431). Median OS for platinum in 2nd line vs. no platinum was 43.6 vs. 37.6 months (p = 0.0174). CONCLUSIONS: Use of non-platinum chemotherapy and even targeted therapy to prolong PFI in patients with EOC recurring between 6 and 12 months leads to worse survival.

Improving cancer care for American Indians with cervical cancer in the Indian Health Service (IHS) system - Navigation may not be enough.

OBJECTIVES: Patient navigation programs have been shown to positively impact cancer outcomes for minority populations. Little is known regarding the effects of these programs on American Indian (AI) populations. The purpose of this study is to characterize the impact of a patient navigation program on AI cervical cancer patients at a tertiary care center. METHODS: A retrospective review of all AI cervical cancer patients receiving navigation services and a cohort of AI patients treated prior to navigation services was performed. Additional comparisons were made between those with and without Indian Health Service (IHS) funding. Summary statistics were used to describe demographic, clinical characteristics, treatment, and survivorship across groups. RESULTS: Of 55 patients identified, 34 received navigation and 21 did not. In navigated patients, median age was 46years (27-80years) compared with 42years (17-68years) in pre-navigation patients (p=0.53). There was no difference between stage at diagnosis (p=0.73). No difference was noted in treatment received between groups (p=0.48). Distance traveled for treatment between groups did not differ (p=0.46). Median time to initiation of treatment was not different between groups, 30.5days vs. 27.5days (p=0.18). Among patients with IHS funding, navigation services did not alter time to initiation of treatment (p=0.57), and there was no difference in completion of prescribed therapy between groups (92% navigated vs 100% pre-navigation). CONCLUSIONS: Navigation services for AI cervical cancer patients did not alter initiation or completion of treatment. Navigation programs may provide less tangible benefits to AI cervical cancer patients and further study is warranted.

Tolerance and toxicity of the PARP inhibitor olaparib in older women with epithelial ovarian cancer.

OBJECTIVES: The objective of this study was to determine the overall tolerability and toxicity of olaparib capsules among older (≥65years) patients with recurrent ovarian cancer treated on 8 completed prospective trials of olaparib. METHODS: An ancillary data analysis of 398 patients with recurrent ovarian cancer enrolled on eight prospective trials of olaparib capsules was performed. Patients aged 65years and older were stratified into age groups by 5year increments (ages 65-69, 70-74, ≥75years) and compared to those <65. Analysis was restricted to those patients receiving the recommended treatment dose of 400mg PO b.i.d. RESULTS: Of the 398 patients included, 78 were ≥65 (age 65-69 n=38, age 70-74 n=23, age≥75 n=17). The majority of elderly patients were Caucasian (n=2 Asian) and had received ≥5 prior lines of chemotherapy. In patients <65, 46.9% required dose reduction as compared to 44.7% of patients 65-69years, 47.8% of patients 70-74years, and 64.7% of patients ≥75years (p=0.62). In patients <65years 41.2% required dose interruption, as compared to 50%, 43.5%, and 64.7% of patients aged 65-69, 70-74, and ≥75, respectively (p=0.11). There were no occurrences of myelodysplastic syndrome or acute myeloid leukemia in any of the older cohorts. Toxicities, including grade 3/4 nausea, were similar across age groups. CONCLUSIONS: Tolerability and toxicity of olaparib capsules is similar between women ≥65years and <65years of age treated for advanced recurrent ovarian cancer. Use of olaparib should be considered in this patient population.