Correlation of imaging and plasma based biomarkers to predict response to bevacizumab in epithelial ovarian cancer (EOC).

PURPOSE: Increasing measures of adiposity have been correlated with poor oncologic outcomes and a lack of response to anti-angiogenic therapies. Limited data exists on the impact of subcutaneous fat density (SFD) and visceral fat density (VFD) on oncologic outcomes. This ancillary analysis of GOG-218, evaluates whether imaging markers of adiposity were predictive biomarkers for bevacizumab (bev) use in epithelial ovarian cancer (EOC). PATIENTS AND METHODS: There were 1249 patients (67%) from GOG-218 with imaging measurements. SFD and VFD were calculated utilizing Hounsfield units (HU). Proportional hazards models were used to assess the association between SFD and VFD with overall survival (OS). RESULTS: Increased SFD and VFD showed an increased HR for death (HR per 1-SD increase 1.12, 95% CI:1.05-1.19 p = 0.0009 and 1.13, 95% CI: 1.05-1.20 p = 0.0006 respectively). In the predictive analysis for response to bev, high VFD showed an increased hazard for death in the placebo group (HR per 1-SD increase 1.22, 95% CI: 1.09-1.37; p = 0.025). However, in the bev group there was no effect seen (HR per 1-SD increase: 1.01, 95% CI: 0.90-1.14) Median OS was 45 vs 47 months in the VFD low groups and 36 vs 42 months in the VFD high groups on placebo versus bev, respectively. CONCLUSION: High VFD and SFD have a negative prognostic impact on patients with EOC. High VFD appears to be a predictive marker of bev response and patients with high VFD may be more likely to benefit from initial treatment with bev.

Consideration of older patients for enrollment in phase 1 clinical trials: Exploring treatment related toxicities and outcomes.

OBJECTIVES: Age imposes a disparity in the treatment of and outcomes with gynecologic cancer. Older patients are underrepresented in primary treatment trials, but little is known about their ability to withstand trial-based treatment for recurrent or refractory disease. This study sought to examine treatment-related toxicities and outcomes of older versus younger patients participating in phase 1 clinical trials. METHODS: A retrospective analysis of patients enrolled in phase 1 clinical trials for gynecologic malignancies from 2010 to 2016 was performed. Demographic and clinic-pathologic data was abstracted. Toxicities were defined as either grade III or IV by CTCAE criteria. Best response was calculated using RECIST criteria. Associations between categorical variables were determined using Fisher's exact test and continuous variables using Wilcoxon rank sum test. Survival was estimated using the Kaplan-Meier method. RESULTS: 237 patients were included with 22% (n=51) comprising the older cohort (≥70years). The vast majority (98%) were treated for recurrent disease. Older patients incurred similar grade III/IV hematologic (21% vs 16%, p=0.38) and non-hematologic toxicities (26% vs 29%, p=0.64). Older patients discontinued treatment due to toxicity only 8% of the time. Median survival was 13.0 and 10.3months in the <70 and ≥70 groups, respectively (p=0.35). 63% of patients ≥70 achieved clinical benefit. CONCLUSIONS: Although historically older patients have not been routinely considered for enrollment in phase 1 trials, our data demonstrates similar toxicity profiles to that of younger patients and 63% clinical benefit rate. Thus, with careful selection, patients ≥70 should be considered when facing recurrent or refractory gynecologic cancer.

Personalized Medicine in Gynecologic Cancer: Fact or Fiction?

Personalized medicine in gynecologic oncology is an evolving field. In recent years, tumor profiling and large databases such as TCGA and NCI-Match have provided us with enormous amounts of molecular data. Several therapies that capitalize on novel genetic and immune discoveries including VEGF inhibitors, PARP inhibitors, and cancer vaccinations are discussed in this article. Additionally, we have seen direct to consumer marketing play an important role in cancer care and prevention as patients have increased ability to access genetic testing. This presents a unique challenge to gynecologic oncology providers as we learn to navigate the world of personalized medicine.

Genetics and the Gynecologic Patient.

Background: The field of hereditary cancer syndromes and genetic testing for patients and families is a rapidly evolving discipline, with an emphasis on cancer prevention. Methods: We review the literature regarding the most common genetic syndromes associated with gynecologic malignancies and discuss the management of these conditions. We also examine the logistic process surrounding cancer genetic testing and identify some perceived barriers. Results: Five genetic syndromes are known to be associated with gynecologic malignancies: hereditary breast and ovarian cancer, Lynch, Cowden, Peutz-Jeghers, and Li-Fraumeni. Each is associated with varying risks of breast, ovarian, and uterine malignancies. The National Comprehensive Cancer Network guidelines regarding the management of these syndromes are focused primarily on reducing the risk of developing gynecologic malignancies. However, great complexity is involved with genetic testing for patients and their families, and barriers exist for the widespread use and implementation of such testing. Conclusion: Genetic testing is fundamental to primary cancer prevention and to oncologic care. Physicians, payers, and institutions must work collaboratively to maximize genetic testing with the goals of primary cancer prevention and treatment.

Personalized Medicine in Gynecologic Cancer: Fact or Fiction?

Personalized medicine in gynecologic oncology is an evolving field. In recent years, tumor profiling and large databases such as TCGA and NCI-Match have provided us with enormous amounts of molecular data. Several therapies that capitalize on novel genetic and immune discoveries including VEGF inhibitors, PARP inhibitors, and cancer vaccinations are discussed in this article. Additionally, we have seen direct to consumer marketing play an important role in cancer care and prevention as patients have increased ability to access genetic testing. This presents a unique challenge to gynecologic oncology providers as we learn to navigate the world of personalized medicine.

Paediatric high dependency provision: a case for urgent review in the United Kingdom.

The issues surrounding paediatric high dependency provision require attention. The field of adult high dependency has revealed some useful studies, which promote the benefits of designated care. These relate to improved quality of care and reduced pressure on the availability of intensive care beds. This review outlines recent initiatives made in the development of paediatric intensive care units in Britain and demonstrates how practical lessons learnt in the adult critical care sector may be used to establish appropriate Level 1 care in paediatrics. Two paediatric clinical issues are reviewed that support the need for high dependency provision, these being: paediatric respiratory management and the management of sedation withdrawal. The options available to district general hospitals, specialist hospitals, as well as lead paediatric hospitals are discussed, and include quality issues, where education, training and clinical audit are integral to structural and staffing HDU considerations.