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Objectives: Poly (ADP-ribose) polymerase inhibitors (PARPis) improve progression-free survival (PFS) in high-grade epithelial ovarian cancer (EOC) as frontline maintenance (FM), platinum sensitive maintenance (PSM) and active therapy (AT) of recurrence. Investigation of PARPi effectiveness within everyday clinical practice is necessary. Using real-world PARPi data we explored survival outcomes by PARPi indication (PI), toxicities and impact on next-line therapy. Methods: A retrospective review was conducted of EOC patients receiving PARPis from 3/2014-3/2020. Medical records were reviewed for clinicopathologic data, PI, treatment details, response, survival and toxicity. Statistics included descriptive, one-way ANOVA, Cox proportional hazard (PH) regression and Wilcoxon Gehan-Breslow survival analyses. Results: 175 patients were included. Mean age at diagnosis was 59.9 years (25.8-93). Most patients had high-grade serous histology (88%), advanced stage (III 62.9%; IV 23.4%) and platinum sensitive disease (84.6%). BRCA status included 54 (30.9%) germline, 5 (2.9%) somatic, 6 (3.4%) homologous recombination deficient and 88 (50.3%) negative. PI included FM (11.4%), PSM (41.7%) and AT (46.9%). PI predicted PFS on PARPi [median (months): FM=18.2, PSM=19.3, AT=6.3, p=0.0001]. On Cox PH regression, age (p=0.03), PI (p=0.001) and PARPi agent (p=0.003) predicted PFS. Of 123 patients with progression (FM=8, PSM=43, AT=72), 97 (78.9%) received next-line therapy including chemotherapy (73.2%), clinical trial (11.3%), VEGF inhibition (5.2%), immune therapy (5.2%), hormones (4.1%) and HIPEC (1.0%). Disease control rate on next-line was 43.3% (Figure 1). PI was not associated with PFS on next-line [median (months): FM=3.5, PSM=3.8, AT=4.4, p=0.48] or number of subsequent lines (mean, FM=1.8, PSM=2.3, AT=2.1, p=0.21). PI predicted overall survival (OS) [median (months): FM-not met, follow-up=27.6, PSM-not met, follow-up=65.7, AT=78.0, p Download : Download high-res image (70KB) Download : Download full-size image Conclusions: PARPi toxicities reflected clinical trial results. Across indications PARPi use did not limit administration or response to subsequent therapies, though patients receiving next-line cytotoxic had notable hematologic toxicity. PFS on PARPi and OS were associated with PI. Future research should aim to identify optimal sequencing of PARPi, and those most likely to benefit from retreatment.

The authors describe a 12-year-old girl with an atypical presentation of Bartonella encephalitis. She presented with fever and altered mental status and developed flaccid paralysis of her left upper extremity a day later. An electroencephalogram showed slowing over her right hemisphere. She had mild leukocytosis and bandemia, but her imaging and cerebrospinal studies were unrevealing. After five days, her symptoms resolved and she was discharged home on doxycycline due to suspicion for Bartonella encephalitis. The patient admitted to playing with a kitten two months prior, but she lacked the classic regional lymphadenopathy. Bartonella titers were sent during her hospitalization and returned positive after her discharge. Cat scratch disease neurologic manifestations are uncommon, with hemiplegia being exceedingly rare. This case illustrates that focal neurologic signs may develop during cat scratch disease infection and suggests that cat scratch disease encephalitis should be considered during evaluation of a pediatric patient with acute flaccid paralysis.