Cancer-associated thrombotic microangiopathy refers to a group of disorders characterised by microvascular thrombosis, thrombocytopenia, and ischaemic end-organ damage. Haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura are the two major subtypes. It can be a manifestation of the malignancy itself or a complication of its therapy. The addition of several new drugs to the therapeutic armamentarium of cancer has brought to light several novel causative factors of this hitherto uncommon complication. This review covers the aetiology, pathogenesis, clinical manifestations, complications, and the management of cancer-associated thrombotic microangiopathy. Careful review of the patient’s medical records coupled with the correlation of clinical findings and laboratory reports can help clinch the diagnosis and institute appropriate treatment on time.

Introduction:Febrile neutropenia (FN) is an oncological emergency. The choice of empiric therapy depends on the locally prevalent pathogens and their sensitivities, the sites of infection, and cost. The Infectious Diseases Society of America guidelines are being followed for the management of FN in India.Methods:This is a prospective observational study conducted at a tertiary care cancer centre from September 2012 to September 2014.Objectives:The objectives of this study were as follows: (1) To review the pattern of microbial flora, susceptibility pattern, and important clinical variables among bloodstream infections in febrile neutropenic patients with solid tumors and hematological malignancies. (2) As per the institutional protocol to periodically review the antibiotic policy and susceptibility pattern, and compare the findings with an earlier study done in our institute in 2010. This was a prospective study conducted from September 2012 to September 2014.Results:About 379 episodes of FN were documented among 300 patients. About 887 blood cultures were drawn. Of these, 137 (15%) isolates were cultured. Isolates having identical antibiograms obtained from a single patient during the same hospitalization were considered as one. Hence, 128 isolates were analyzed. About 74 (58%) cultures yielded Gram-negative bacilli, 51 (40%) were positive for Gram-positive cocci, and 3 (2%) grew fungi. Among Gram-negative organisms, Escherichia coli followed by Acinetobacter baumannii and Klebsiella pneumoniae accounted for 78% of the isolates. Among Gram-positive cocci, Staphylococcus species accounted for 84% of the isolates. We have noted a changing trend in the antibiotic sensitivity pattern over the years. Following the switch in empirical antibiotics, based on the results of the study done in 2010 (when the empirical antibiotics were ceftazidime + amikacin), the sensitivity to cefoperazone-sulbactam has plunged from about 80% to 60%%. Similar reduction in susceptibility was noted for piperacillin-tazobactam, imipenem, and meropenem. On the contrary, there was a marked increase in sensitivity to ceftazidime (50–76%). Based on these results, we have reverted to ceftazidime + amikacin as the empirical antibiotics.Conclusion:Every institute must have a regular revision of antibiotic policy based on periodic assessment of the clinical and microbiological profile in FN. This will combat antibiotic resistance.

Epithelial ovarian cancer (EOC) remains a lethal disease for the majority of women diagnosed with it worldwide. For the majority of patients, diagnosis occurs late, in the advanced setting. Disease-induced as well as treatment-related adverse events can negatively impact quality of life (QoL). Research to date has captured these data through use of patient-related outcomes (PROs) and, increasingly, has become an area of increased attention and focus in clinical trial reporting. QoL/PRO measurements in EOC clinical trials at different transition points in a patient’s journey are increasingly being recognized by patients, clinicians and regulatory agencies as the key determinants of treatment benefit. Various context-specific PROs and PRO endpoints have been described for clinical trials in EOC. Standardized approaches and checklists for incorporating PRO endpoints in clinical trials have been proposed. In a real-world clinical practice setting, PRO/QoL measures, which are meaningful, valid, reliable, feasible and acceptable to patients and clinicians, need to be implemented and used. These may assist by serving as screening tools; helping with the identification of patient preferences to aid in decision making; improving patient–provider communication; facilitating shared decision making. Importantly, they may also improve quality of care through an increasingly patient-centered approach. Potential areas of future research include assessment of anxiety, depression and other mental health issues. In good prognostic groups, such as maintenance clinical trials, following patients beyond progression will capture possible downstream effects related to delaying the psychological trauma of relapse, symptoms due to disease progression and side-effects of subsequent chemotherapy. Identifying PRO endpoints in next-generation-targeted therapies (including immunotherapies) also warrants investigation.

5521 Background: PARP inhibitors (PARPi) are approved therapies in high grade serous ovarian cancer (HGSOC). There are few studies after PARPi progression and correlation with dynamic changes in resistance. We hypothesized that PARPi resistance could be overcome by adding an anti-angiogenic. Methods: We report the first phase 2 trial assessing the combination of olaparib and cediranib after PARPi failure in HGSOC. This investigator initiated study included three cohorts of 10 evaluable patients (pts): i) platinum sensitive post PARPi (PS), ii) platinum resistant post PARPi (PR) and iii) exploratory cohort of pts re-challenged with chemotherapy post PARPi progression (PE) (NCT02681237). The primary objective was to determine objective response rate by RECIST v1.1 and progression free survival (PFS) at 16 weeks. Secondary objectives were to evaluate safety, PFS, overall survival (OS) and mechanisms of PARPi resistance. Pts who had radiographic progression on any PARPi were eligible. Archival tumor at initial diagnosis and baseline tumor biopsy at PARPi progression were mandatory. Pts received olaparib tablets 150mg BID with cediranib 20mg QD until progression or unacceptable toxicity. CT scans were performed every 8 weeks. Whole exome and RNA sequencing were performed on paired tumors tissues. Results: Thirty-four pts were enrolled. BRCA1/2 mutations were found in 9/11 PS, 8/10 PR and 7/13 PE pts. By RECIST1.1, four partial responses were observed (2 in PR and 2 in PE cohorts) and 18 stable disease. The 16−week PFS was 54.5% (31.8−93.6) in PS, 50% (26.9−92.9) in PR and 36% (15.6−82.8) in PE, respectively. OS at 1 year was 81.8% (61.9−100) in PS, 64.8% (39.3−100) in PR and 39.1% (14.7−100) in PE. Main related adverse events were anemia, hypertension, diarrhea and fatigue, grade 3 < 10%. Molecular analyses identified different mechanisms of PARPi resistance in ~77% of evaluable pts with matched pre-post PARPi progression biopsies such as reversion mutations in BRCA1/2 and other homologous repair (HR) genes; BRCA, HR and MDR upregulation, CCNE amplification and RIG-I like receptor downregulation. Conclusions: Treatment with olaparib-cediranib after PARPi failure was feasible and met the predefined bar for efficacy in each cohort. This is the largest clinical trial prospectively evaluating PARPi failure and correlating tissue genomic mechanisms of resistance. Clinical trial information: NCT02681237.