ARAP1 is an independent prognostic biomarker in older women with ovarian high-grade serous adenocarcinoma receiving first-line platinum-based antineoplastic therapy.

Background: Little is known about the biological factors influencing ovarian cancer (OC) patient outcome, especially in older patients who are often underrepresented in clinical trials. We examined alterations in the transcriptomic profile of primary high-grade serous carcinoma (HGSC) samples from older OC patients (>70 years) receiving first-line platinum-based treatment to identify potential biomarkers for prediction of response to this therapy.Material and methods: Tumor samples from 50 HGSC patients were identified from a retrospective cohort, analyzed by gene expression array. The protein expression of selected biomarkers was examined using immunohistochemistry (IHC).Results: Gene expression profiling revealed 81 genes with significantly altered expression in patients experiencing progression after first-line platinum-based treatment within 6 months versus those who progressed later than 12 months. Expression of ankyrin repeat and PH domain 1 (ARAP1) was significantly lower in the group with early versus late progression (p ≤ .01). Correlation between ARAP1 expression and outcome was further confirmed by IHC staining in the discovery cohort (χ2-test, p = .004) and in independent validation cohorts. The sensitivity of ARAP1 allowed identification of 64.7% of patients with early progression in the discovery population, with a specificity of 78.6% and a negative predictive value of 78.6%. Multivariate regression analysis identified ARAP1 as an independent prognostic factor.Conclusions: This hypothesis generating study suggests that low expression of ARAP1 is an independent prognostic biomarker of shorter RFS in older patients with HGSC receiving first-line platinum-based antineoplastic therapy, which could be used to identify patients who should receive more intensive treatment and closer surveillance.

Palonosetron for the prevention of nausea and vomiting in children with acute lymphoblastic leukemia treated with high dose methotrexate.

BACKGROUND: High dose methotrexate (HD-MTX), used in the treatment of children with acute lymphoblastic leukemia (ALL), is moderately emetogenic. First generation 5-HT(3) receptor antagonists are effective prophylactic agents but require multiple administrations. Palonosetron has a half life of 36-42 hours and has higher affinity and selectivity to the 5-HT(3) receptor. Adult studies have demonstrated that palonosetron is both more effective and require fewer administrations than first generation 5-HT(3) receptor antagonists. The purpose of this study was to examine the effect of a single dose of palonosetron (5 µg/kg) for the prevention of chemotherapy-induced nausea and vomiting in children 18 years of age with ALL treated with HD-MTX, 5 g/m(2). PROCEDURE: Between January 2010 and December 2010, 138 courses, originating from 53 children, were included from four Danish Childhood Cancer Centers. Information regarding emetic episodes, rescue therapy, and nausea were recorded prospectively on questionnaires. RESULTS: Complete response (no emesis and no rescue therapy) was achieved in 84.1% of courses during the acute (0-24 hours post-chemotherapy) and in 60.1% during the delayed phase (24-66 hours post-chemotherapy). 92.0% of courses were free of emesis during the acute, and 86.2% were free of emesis during the delayed phase. 76.8% of courses were free of nausea during the acute, and 78.3% were free of nausea during the delayed phase. CONCLUSIONS: A single dose of palonosetron--without concomitant corticosteroid--was effective in preventing both acute and delayed phase CINV in majority of children with ALL treated with HD-MTX.

The impact of comprehensive geriatric assessment for optimal treatment of older patients with cancer: A randomized parallel-group clinical trial.

OBJECTIVES: The aim was to investigate if oncologic treatment decision based on G8 screening followed by comprehensive geriatric assessment (CGA) and a multidisciplinary team conference in patients with G8 ≤ 14 was better than treatment decision based on standard assessment. ClinicalTrials.gov Identifier: NCT02671994. MATERIALS AND METHODS: From January 2016 to June 2018, 96 patients with cancer, aged ≥70 years, were included. Patients were randomized to treatment decision based on the oncologist's clinical judgement (control) or based on screening with G8. If G8 > 14 treatment decision was made as in the control group and if G8 ≤ 14, patients were referred to CGA including intervention as needed and treatment decision after a multidisciplinary team conference (MDT). RESULTS: The study was closed early. 47 patients were randomized to the control group and 49 to the intervention group; 28 had a G8 ≤ 14, 24 of whom attended CGA. In the intervention group 48% completed treatment as planned compared to 54% in the control group (p = .208). Thirty-eight percent experienced grade 3-4 toxicity in the control group compared with only 20% in the intervention group (p = .055). Median overall survival (OS) was 14.2 months in the control group and 19.1 months in the intervention group (p = .911). Median progression-free survival (PFS) was 9.0 months in the control group and 7.8 months for the intervention group (p = .838). CONCLUSION: Treatment decision based on G8 screening followed by CGA had no impact on completion rate of planned oncologic treatment, OS or PFS, but resulted in a borderline significant lower incidence of grade 3-4 toxicity.

Impact of Age, Comorbidity, and FIGO Stage on Treatment Choice and Mortality in Older Danish Patients with Gynecological Cancer: A Retrospective Register-Based Cohort Study.

BACKGROUND: The number of older patients with cancer is increasing in general, and ovarian and endometrial cancer are to a large extent cancers of the elderly. Older patients with cancer have a high prevalence of comorbidity. Comorbidity and age may be predictive of treatment choice and mortality in older patients with cancer along with stage and performance status. OBJECTIVES: The aim of this study was to describe comorbidity in a population of older Danish patients with gynecological cancer, and to evaluate the predictive value of comorbidity and age on treatment choice and cancer-specific and all-cause mortality. MATERIALS AND METHODS: In this retrospective study, we included 459 patients aged ≥ 70 years. Patients were diagnosed with cervical, endometrial, or ovarian cancer from 1 January, 2007 to 31 December, 2011 and were evaluated and/or treated at Odense University Hospital. Comorbidity was assessed using the Charlson Comorbidity Index. Treatment was classified as curative intended, palliative intended, or no treatment. RESULTS: Age, International Federation of Gynecology and Obstetrics (FIGO) stage, and performance status were found to be significant predictors of treatment choice, while comorbidity was not. Multivariate analyses showed that both cancer-specific and all-cause mortality were significantly associated with treatment choice, FIGO stage, and performance status. Age was not associated with mortality, with the exception of ovarian cancer, where age was associated with all-cause mortality. Comorbidity was not an independent predictor of treatment choice or mortality. CONCLUSIONS: In our population of older Danish patients with gynecological cancer, age, FIGO stage, and performance status were predictors of treatment choice, while comorbidity was not. Treatment choice, FIGO stage, and performance status were significantly associated with both cancer-specific and all-cause mortality. Age was only associated with mortality in ovarian cancer, while comorbidity was not associated with mortality.