Healthcare and economic impact of diarrhea in patientswith carcinoid syndrome

AIM To examine healthcare resource utilizationpatterns and costs accrued by carcinoid syndrome （CS）patients with and without diarrhea.METHODS： We conducted a retrospective cohort studyusing MarketScan data from 1/1/2002-12/31/2012.Newly diagnosed CS patients had 1 medical claim forCS （ICD-9-CM code 259.2） plus either ≥ 1 additionalclaim for CS or for carcinoid tumors （ICD-9-CM 209.x）, and had no evidence of CS for 1 year prior to index CS diagnosis, in commercially-insured patients 〈 65years old. Patients were required to have continuousenrollment one year prior and after index date （firstclaim with CS diagnosis in the ID period）. We identifiedpatients with evidence of non-infectious diarrhea （ICD-9-CM codes 564.5 and 787.91） within one year from theindex date. Overall and CS-related healthcare resourceutilization and costs were compared between patientswith and without non-infectious diarrhea during theone year period after the index date.RESULTS： There were 2822 newly diagnosed CSpatients; 534 （18.9%） had evidence of non-infectiousdiarrhea. Compared to patients without non-infectiousdiarrhea, non-infectious diarrhea patients morecommonly had at ≥ 1 CS-related hospitalization（13.7% vs 7.2%）, ≥ 1 CS-related ED visit （11.0% vs4.4%）, and CS-related office visits in one year （6.9 vs4.1; all p 〈 0.001）. After adjusting for demographics,region, number of chronic conditions and the CharlsonComorbidity Index, the proportions of patients withany and with CS-related hospitalizations were 9.7%and 6.8% higher, respectively, among non-infectiousdiarrhea patients compared to those with without noninfectiousdiarrhea （p 〈 0.001）. Unadjusted costs weresignificantly higher among non-infectious diarrheapatients vs those without non-infectious diarrhea. Thenon-infectious diarrhea group was also more costly,with adjusted mean annual costs of $81610, comparedto $51719 in the group without non-infectious diarrhea（p 〈 0.001）.CONCLUSION： Diarrhea is burdensome and costlyin CS patients. Reduction of CS-related healthcareexpenditures may be achievable through preventivetreatment and appropriate management of diarrhea inCS.

Real-world treatment patterns of gastrointestinal neuroendocrine tumors: A claims database analysis

AIM To describe real-world treatment patterns of gastrointestinal neuroendocrine tumors(GI NET).METHODS In this retrospective cohort study,we used 2009-2014 data from 2 United States commercial claims databases to examine newly pharmacologically treated patients using tabular and graphical techniques. Treatments included somatostatin analogues(SSA),cytotoxic chemotherapy(CC),targeted therapy(TT),interferon(IF) and combinations. We identified patients at least 18 years of age,with ≥ 1 inpatient or ≥ 2 outpatient claims for GI NET who initiated pharmacologic treatment from 7/1/09-6/30/14. A 6 mo clean period prior to first treatment ensured patients were newly treated. Patients were followed until end of enrollment or the study end date,whichever was first.RESULTS We identified 2258 newly treated GI NET patients: mean(SD) age was 55.6 years(SD = 9.7),47.2% of the patients were between 55 and 64 years,and 48.8% were female. All regions of the United States were represented. 59.6% started first-line therapy with SSA monotherapy(964 with octreotide LAR,380 with octreotide SA,and 1 with lanreotide),33.3% CC,3.6% TT,and 0.5% IF. The remainder received combinations. Mean follow up was 576 d. Overall mean first-line therapy duration was 361 d(449 d for SSA,215 for CC,267 for TT). 58.9% of patients had no pharmacological treatment beyond first line. The most common secondline was combination therapy with SSA. In graphical pattern analysis,there was no clear pattern visible after first line therapy.CONCLUSION In this study,60% of patients initiated treatment with SSA alone or in combination. The relatively long time to discontinuation suggests possible sustained effectiveness and tolerability.

Gastrointestinal neuroendocrine tumors treated with high dose octreotide-LAR:A systematic literature review

AIM:To review literature on efficacy and safety of octreotide-long-acting repeatable(LAR)used at doses higher than the Food and Drug Administration(FDA)-approved 30 mg/mo for treatment of neuroendocrine tumors(NETs).METHODS:We searched Pub Med and Cochrane Library from 1998-2012,5 conferences(American Society of Clinical Oncology,Endocrine Society,European Neuroendocrine Tumor Society,European Society for Medical Oncology,North American Neuroendocrine Tumor Society)from 2000-2013 using Me SH and keyterms including neuroendocrine tumors,carcinoid tumor,carcinoma,neuroendocrine,and octreotide.Bibliographies of accepted articles were also searched.Two reviewers reviewed titles,abstracts,and full-length articles.Studies that reported data on efficacy and safety of≥30 mg/mo octreotide-LAR for NETs in human subjects,published in any language were included in the review.RESULTS:The search identified 1086 publications,of which 238 underwent full-text review(20 were translated into English);17 were included in the review.Studies varied in designs,subjects,octreotide-LAR regimens,and definition of outcomes.Eleven studies reported use of higher doses to control symptoms and tumor progression,although symptom severity and formal quality-of-life analysis were not quantitatively measured.Ten studies reported efficacy,describing 260 subjects with doses ranging from 40 mg/mo or 30 mg/3 wk up to 120 mg/mo.Eight studies reported expert clinical opinion that supported dose escalation of octreotide-LAR up to 60 mg/mo for symptom control and suggested increased doses may be effective at preventing tumor progression.Eight studies reported safety;there was no evidence of increased toxicity associated with doses of octreotide-LAR>30 mg/mo.CONCLUSION:As reported in this review,octreotide-LAR at doses>30 mg/mo is being prescribed for symptom and tumor control in NET patients.Furthermore,expert clinical opinion provided support for escalation of somatostatin analogs for refractory hormonal symptoms.