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Objective@#To describe the gene alteration status in high-grade neuroendocrine cervical carcinoma (NECC) specimens and to explore the potential association of unique gene alterations with survival. @*Methods@# @*Results@#from tumor-based molecular testing on specimens from women with high-grade NECC in the Neuroendocrine Cervical Tumor Registry were reviewed and analyzed. Tumor specimens could be from primary or metastatic sites and obtained at initial diagnosis, during treatment, or at recurrence. @*Results@#Molecular testing results were available for 109 women with high-grade NECC. The genes most frequently mutated were PIK3CA (mutated in 18.5% of patients), TP53 (17.4%), and MYC (14.5%). Other targetable alterations identified were alterations in KIT (7.3%), KRAS (7.3%), and PTEN (7.3%). Women with tumors having an RB1 alteration (6.4%) had a median overall survival (OS) of 13 months, compared to 26 months for women with tumors that did not have an RB1 alteration (p=0.003). None of the other genes evaluated were shown to be associated with OS. @*Conclusion@#Although no individual alteration was found in a majority of tumor specimens from patients with high-grade NECC, a large proportion of women with this disease will have at least one targetable alteration. Treatments based on these gene alterations may offer additional targeted therapies for women with recurrent disease, who currently have very limited therapeutic options. Patients with tumors that harbor RB1 alterations have decreased OS.
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PURPOSE: The response to haloperidol as a first-line neuroleptic and the pattern of neuroleptic rotation after haloperidol failure have not been well defined in palliative care. The purpose of this study was to determine the efficacy of haloperidol as a first-line neuroleptic and the predictors associated with the need to rotate to a second neuroleptic. MATERIALS AND METHODS: We conducted a retrospective review of the charts of advanced cancer patients admitted to our acute palliative care unit between January 2012 and March 2013. Inclusion criteria were a diagnosis of delirium and first-line treatment with haloperidol. RESULTS: Among 167 patients with delirium, 128 (77%) received only haloperidol and 39 (23%) received a second neuroleptic. Ninety-one patients (71%) who received haloperidol alone improved and were discharged alive. The median initial haloperidol dose was 5 mg (interquartile ranges [IQR], 3 to 7 mg) and the median duration was 5 days (IQR, 3 to 7 days). The median final haloperidol dose was 6 mg (IQR, 5 to 7 mg). A lack of treatment efficacy was the most common reason for neuroleptic rotation (87%). Significant factors associated with neuroleptic rotation were inpatient mortality (59% vs. 29%, p=0.001), and being Caucasian (87% vs. 62%, p=0.014). Chlorpromazine was administered to 37 patients (95%) who were not treated successfully by haloperidol. The median initial chlorpromazine dose was 150 mg (IQR, 100 to 150 mg) and the median duration was 3 days (IQR, 2 to 6 days). Thirteen patients (33%) showed reduced symptoms after the second neuroleptic. CONCLUSION: Neuroleptic rotation from haloperidol was only required in 23% of patients with delirium and was associated with inpatient mortality and white race.