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Cytoreduction and hyoerthermic intraperitoneal chemotherapy in peritoneal
carcinomastosis of colorectal origin
Verwaal, V.J.
Publication date
2004
Link to publication
Citation for published version (APA):
Verwaal, V. J. (2004). Cytoreduction and hyoerthermic intraperitoneal chemotherapy in
peritoneal carcinomastosis of colorectal origin.
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Chapterr eight
Costt effectiveness and quality of life analysis
Vicc J. Verwaai
1, Els M. Ten Vergert
2, Wendy J. Post
2, Neil Aaronson
3andd Martin Muller
3d e p a r t m e n tt of Surgery and
3Division of Psychosocial Research & Epidemiology
Thee Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital,
Amsterdam,, the Netherlands
2Officee for Medical Technology Assessment, Groningen University Hospital
Groningen,, the Netherlands
BackgroundBackground Cytoreduction plus HIPEC is a promising treatment for peritoneal carcinomatosis. This novel
treatmentt is known to be extensive and can be accompanied by major complications. It therefore is ques-tionablee whether this treatment is cost effective.
Method:Method: Within the patient population of the randomized trial comparing standard treatment to
cytoreduc-tionn and HIPEC, direct and indirect medical costs are calculated and compared between both arms. Quality off life was calculated from questionnaires, which were filled out at randomization and at regular interval thereafter. .
Results:Results: The direct medical costs of cytoreduction and HIPEC were 27,135 €. The costs-efficacy ration was
26,6200 / 1.54 = 17,286 €. Quality of life and physical, social and role functioning were significantly de-creasedd at six weeks in patients in the hyperthermic intraperitoneal chemotherapy group, fatigue, insomnia, vomiting,, nausea and appetite loss were increased. After three months, the only remaining significant differ-encess concerned physical functioning and role functioning. AJJ the differences between the arms had disap-pearedd at six months.
Costss and QoL
Thee design of the randomized trial of hyperthermic intraperitoneal chemotherapy in patients with peritoneall carcinomatosis of colorectal cancer contained a cost effectiveness and quality of life analysis.. In this trial, 58 men and 47 women with a median age of 54 years (range 28-70 years) were randomizedd to either palliative surgery and systemic chemotherapy (standard arm) or cytoreduction andd hyperthermic intraperitoneal chemotherapy (HIPEC)(experimental arm). Two patients were excludedd from the current analysis. Both were ineligible after revision of the histology, one in the controll arm and one in the experimental arm. The purpose of die analysis was to compare eco-nomicall and quality of life consequences in the two groups.
Thee cost effectiveness evaluation was based on both medical and non-medical impact of the treatments.. To estimate the actual medical costs of cytoreduction and HIPEC, real costs were countedd in 18 randomly selected patients out of die group 48 patients who received diis therapy. Thee costs of personnel, use of equipment and none-disposables were estimated based on informa-tionn of experts within The Nedierlands Cancer Institute. The costs after the initial treatment were derivedd from questionnaires, which were given to all patients during the three-monthly follow-up visits.. The costs were categorized as direct medical costs (in-hospital and outpatient), and direct non-medicall costs. The Kaplan Meier method was used to estimate survival. The Weibull model waswas used to calculate long-term survival.
Thee costs for cytoreduction and HIPEC during die hospital stay are summarized in table 1. The costss of die systemic chemotherapy were € 4,358 in patients treated in die standard arm and € 3,0400 in the patients treated in the experimental arm. The difference is due to the fact that more patientss in the control arm received chemodierapy dian in the HIPEC arm. Table 2 summarizes thee average costs per randomized patient.
Tablee 2 provides a macro-economical view on the costs. The average costs are based on the ini-tiall number of patients in each arm, and not on the number of patients alive at each point in time. Thee difference in costs between the two arms is attributed to the increased survival time in the cy-toreductionn and HIPEC arm.
Thee average costs of subsequent medical treatment per patient alive for each point in time are shownn in table 3. This table demonstrates that the average medical costs per patient at each
mo-mentt were equal or higher in the control arm patientss compared to the experimental arm. Tablee 1. Average hospital costs of cytore- This probably means that the same amount of ductionn followed by HIPEC medical treatment is needed in patients in both Costs11 arms after initial therapy. Thus, cytoreduction widii HIPEC does not seem to generate a need forr additional subsequent treatment.
Thee € 26,621 difference in all costs between pa-tientstients treated by palliative surgery and those treatedd by cytoreduction and HIPEC is not in favorr of the experimental treatment. The ran-'basedd on 18 randomly selected patients. domized study demonstrated an estimated sur-Pre-operativee 884
Peri-operativee 5,563 Post-operativee 20,688 Totall 27,135
Chapterr 8
Tablee 2. C o m p a r i s o n of average costs of both trial arms
Averagee costs per patient (€)
Controll patients (N=50) HIPEC treated patients (N=53)1
Inclusionn 198 327 HIPECC treatment - 24,576 Systemicc chemotherapy 4,667 3,170 Eirstt year follow-up 9,408 5,875 Secondd year follow-up 4,091 5,480 Thirdd year follow-up 951 2,950 Fourthh year follow-up 213 2,187 Fifthh year follow-up - 1,583 Totall costs 19,528 46,149 'inn this analysis are all patients in the HIPEC arm included, even those who did not
re-ceivee the assigned treatment.
vivall difference o f 1.54 years in favor of the experimental treatment. Consequently, the cost-efficacyy ratio is € 26,620 / 1.54 = € 17,286 per year of life gained.
T h ee quality of life analysis was designed to compare the physical and psychosocial impact of pal-liativee surgery and systemic chemotherapy to the impact of cytoreduction and H I P E C . T h e quality off life was measured with the E O R T C Q L Q - C 3 0 and E O R T C Q L Q CR-38 questionnaires. T h e E O R T CC Q L Q - C 3 0 is a general quality of life questionnaire, while E O R T C Q L Q CR-38 is specific forr colorectal cancer related problems.
T h ee first questionnaires were completed at the time of randomization for baseline measurement. S u b s e q u e n tt questionnaires were completed six weeks later and three-monthtly thereafter. This de-signn enables longitudinal analysis as well as comparison between b o t h treatments.
T h ee response rate was low and the questionnaires were returned at irregular intervals. This was partlyy due to administrative and m a n a g e m e n t problems in the trial. In only 44 patients (42%), there wass a baseline m e a s u r e m e n t and at least a subsequent one. D u e to this low response rate, analyses weree d o n e only at the outset, at six weeks, and at three and six m o n t h s .
N oo difference was found in the baseline measurements between b o t h treatments. General quality off life and physical, social and role functioning were significandy decreased at six weeks in patients inn die H I P E C group. In this same g r o u p , fatigue, insomnia, vomiting, nausea and appetite loss weree increased. After three m o n t h s , the only remaining significant differences concerned physical andd role functioning. All the differences between the arms had disappeared at six m o n t h s (tables 4 andd 5).
T h ee p r e s e n t e d quality o f life analysis has some major weak points. T h e low response rate and the widee range of b o t h medical and quality of life results made analysis difficult. T h e median survival timee o f o n e year in the control arm h a m p e r e d a longitudinal comparison after six months.
Costss and QoL
Nevertheless,, it is clear that the quality of life after cytoreduction and HIPEC is impaired in the postoperativee period. Once recovered, the quality of life is similar in both groups. The obvious ex-planationn for this observation is that patients do not have a long-term impairment of quality of life afterr cytoreduction and HIPEC. However, another explanation could be that the quality of life is decreasedd in both arms, in the experimental arm because of the treatment and in the standard arm becausee of early recurrence.
Thee cost analysis and the quality of life analysis were both based on the initial randomized trial. A substantiall part of the costs in the experimental arm was generated by complications ensuing in prolongedd hospitalization. These costs will probably diminish when better selection results in lower complicationn rates. Better selection will also result in a smaller decrease in quality of life shortly af-terr the treatment.
Tablee 3. Comparison of actual medical costs in euro's per follow-up period per patient Controll (N=50) HIPEC (N=53) 0-33 months 4-66 months 7-99 months 10-122 months 13-155 months 16-188 months 19-211 months 22-244 months 25-277 months 28-300 months 31-333 months 34-366 months 4thh year 5thh year Costs s 2,411 1 1,468 8 3,020 0 2,291 1 2,667 7 1,682 2 4,260 0 982 2 1,705 5 2,327 7 2,327 7 2,327 7 9,308 8 9,308 8 Estimatedd survival 0.97 7 0.87 7 0.73 3 0.60 0 0.47 7 0.36 6 0.27 7 0.20 0 0.14 4 0.10 0 0.07 7 0.04 4 0.02 2 0 0 Costs s 1,247 7 1,118 8 1,325 5 1,371 1 1,291 1 3,066 6 1,680 0 2,015 5 460 0 1,805 5 1,805 5 1,805 5 7,221 1 7,221 1 Estimatedd s 0.94 4 0.85 5 0.77 7 0.70 0 0.64 4 0.58 8 0.53 3 0.49 9 0.45 5 0.41 1 0.37 7 0.34 4 0.28 8 0.20 0
Chapterr 8 T a b l ee 4. Quality of life at E O R T CC Q L Q C30 Physicall functioning1 Rolee functioning1 Cognitivee functioning1 Emotionall functioning1 Sociall functioning1 Globall quality of life1
Fatigue2 2
Nauseaa and vomiting2 Pain2 2 Dyspnea2 2 Insomnia2 2 Appetitee loss2 Constipation2 2 Diarrhea2 2 Financiall impact2 E O R T CC Q L Q CR-38 Bodyy image1 Sexuall functioning1 Sexuall enjoyment1 Futuree perspective1 Micturitionn problems2 Gastrointestinall tract2 Chemotherapyy side effects2
Defecationn problems2 Weightt loss2 baselinee and Experime e N N 34 4 34 4 34 4 34 4 34 4 33 3 34 4 34 4 34 4 34 4 34 4 34 4 34 4 34 4 33 3 34 4 27 7 13 3 34 4 34 4 34 4 34 4 25 5 34 4 Mean n 87.4 4 72.5 5 89.7 7 71.1 1 79.9 9 74.7 7 27.5 5 9.8 8 20.1 1 7.8 8 29.4 4 16.7 7 14.7 7 13.7 7 5.1 1 89.7 7 74.1 1 38.5 5 41.2 2 15.0 0 20.8 8 14.4 4 10.3 3 25.5 5
att six weeks Baseline e ntal l SD D 15.4 4 27.2 2 13.6 6 26.4 4 24.5 5 17.2 2 21.4 4 22.1 1 21.2 2 14.4 4 28.1 1 26.3 3 26.2 2 26.1 1 14.7 7 18.4 4 18.7 7 30.0 0 30.8 8 15.2 2 15.6 6 18.5 5 9.2 2 31.8 8 N N 24 4 24 4 24 4 24 4 24 4 24 4 24 4 24 4 24 4 24 4 24 4 24 4 23 3 23 3 24 4 24 4 20 0 11 1 24 4 24 4 24 4 24 4 17 7 24 4 Control l Mean n 81.9 9 72.9 9 93.1 1 66.8 8 78.5 5 72.9 9 21.3 3 5.6 6 19.4 4 2.8 8 22.2 2 11.1 1 11.6 6 17.4 4 5.6 6 91.7 7 64.2 2 45.5 5 40.3 3 15.7 7 21.1 1 3.7 7 9.0 0 8.3 3 SD D 15.8 8 22.4 4 16.2 2 21.8 8 21.7 7 15.2 2 16.7 7 12.7 7 18.2 2 9.4 4 27.2 2 21.2 2 19.1 1 28.2 2 16.1 1 17.0 0 25.5 5 34.2 2 27.8 8 17.6 6 12.2 2 7.8 8 10.6 6 17.7 7 Afterr 6 weeks Experimental l N N 17 7 17 7 17 7 17 7 17 7 17 7 17 7 17 7 17 7 17 7 17 7 17 7 17 7 17 7 17 7 17 7 14 4 2 2 17 7 17 7 17 7 16 6 7 7 17 7 Mean n 57.9 9 32.4 4 76.5 5 65.5 5 60.8 8 56.9 9 60.1 1 13.7 7 25.5 5 19.6 6 45.1 1 47.1 1 3.9 9 31.4 4 11.8 8 57.8 8 92.9 9 50.0 0 47.1 1 22.9 9 25.9 9 41.0 0 16.3 3 19.6 6 SD D 18.5 5 24.6 6 23.6 6 26.1 1 27.6 6 14.8 8 22.9 9 16.9 9 24.4 4 20.6 6 33.2 2 33.5 5 11.1 1 38.1 1 28.7 7 36.9 9 14.2 2 70.7 7 29.0 0 23.1 1 14.5 5 27.1 1 13.1 1 29.0 0 N N 18 8 18 8 18 8 18 8 18 8 18 8 18 8 18 8 18 8 18 8 18 8 18 8 18 8 18 8 18 8 18 8 14 4 7 7 18 8 18 8 18 8 18 8 13 3 18 8 Contro o Mean n 78.1 1 72.2 2 88.9 9 78.2 2 78.7 7 69.9 9 33.3 3 11.1 1 19.4 4 7.4 4 20.4 4 14.8 8 3.7 7 22.2 2 9.3 3 88.0 0 70.2 2 42.9 9 53.7 7 24.7 7 23.3 3 18.5 5 8.8 8 13.0 0 SD D 21.5 5 31.8 8 16.2 2 19.2 2 30.1 1 21.4 4 28.0 0 15.1 1 26.4 4 18.3 3 20.3 3 20.5 5 10.8 8 28.0 0 25.1 1 25.4 4 23.7 7 31.7 7 25.9 9 18.1 1 18.8 8 16.2 2 9.5 5 25.9 9 h i g h e rr score relates to better function, 2higher score relates to more dysfunction
Costss and QoL
Tablee 5. Quality of life at
EORTCC Q L Q C30 Physicall functioning1 Rolee functioning1 Cognitivee functioning1 Emotionall functioning1 Sociall functioning1 Globall quality of life1 Fatigue2 2
Nauseaa and vomiting2 Pain2 2 Dyspnea2 2 Insomnia2 2 Appetitee loss2 Constipation2 2 Diarrhea2 2 Financiall impact2 EORTCC Q L Q CR-38 Bodyy image1 Sexuall functioning1 Sexuall enjoyment1 Futuree perspective1 Micturitionn problems2 Gastrointestinall tract2
Chemotherapyy side effects2 Defecationn problems2
Weightt loss2
threee m o n t h s andd at six months s Afterr 3 months Experimental l N N 21 1 21 1 21 1 21 1 21 1 21 1 21 1 21 1 21 1 21 1 21 1 20 0 21 1 21 1 21 1 21 1 15 5 7 7 21 1 21 1 21 1 21 1 12 2 21 1 Mean n 69.4 4 52.4 4 83.3 3 76.2 2 73.0 0 67.1 1 46.3 3 15.9 9 19.8 8 14.3 3 20.6 6 13.3 3 1.6 6 30.2 2 6.3 3 78.6 6 81.1 1 61.9 9 58.7 7 17.7 7 23.8 8 27.5 5 15.9 9 14.3 3 'higherr score relates to better function, 2hi
SD D 19.5 5 28.5 5 17.5 5 20.3 3 23.3 3 17.0 0 17.7 7 20.7 7 22.7 7 19.9 9 22.3 3 19.9 9 7.3 3 27.7 7 17.1 1 22.4 4 16.5 5 35.6 6 29.6 6 19.2 2 12.9 9 14.7 7 13.7 7 22.5 5 N N 20 0 20 0 20 0 20 0 20 0 20 0 20 0 20 0 20 0 20 0 20 0 20 0 20 0 20 0 20 0 20 0 15 5 6 6 19 9 20 0 20 0 20 0 13 3 20 0 Contro o Mean n 82.7 7 80.0 0 90.0 0 79.6 6 79.2 2 72.5 5 33.1 1 18.3 3 18.3 3 6.7 7 10.0 0 16.7 7 3.3 3 23.3 3 10.0 0 82.5 5 72.2 2 55.6 6 54.4 4 18.9 9 20.3 3 21.1 1 10.3 3 15.0 0 I I SD D 16.0 0 28.4 4 15.7 7 23.5 5 27.5 5 18.6 6 22.1 1 25.9 9 20.2 2 13.7 7 15.7 7 25.4 4 10.3 3 30.8 8 24.4 4 26.8 8 25.7 7 17.2 2 27.7 7 13.0 0 16.0 0 23.1 1 11.1 1 27.5 5 gherr score relates to more
Afterr 6 months Experimen n N N 21 1 21 1 21 1 21 1 21 1 21 1 21 1 21 1 21 1 21 1 21 1 21 1 21 1 21 1 21 1 21 1 14 4 6 6 21 1 20 0 21 1 21 1 9 9 21 1 Mean n 78.7 7 61.1 1 80.2 2 73.4 4 73.0 0 71.4 4 34.4 4 15.1 1 19.0 0 4.8 8 22.2 2 11.1 1 .0 0 34.9 9 12.7 7 77.0 0 85.7 7 50.0 0 57.1 1 20.3 3 21.3 3 23.8 8 19.6 6 14.3 3 dysfunction n tal l SD D 23.5 5 30.9 9 25.6 6 22.0 0 32.3 3 19.6 6 27.4 4 21.7 7 21.9 9 12.0 0 24.3 3 26.5 5 .0 0 37.2 2 22.3 3 24.4 4 15.8 8 27.9 9 31.9 9 24.3 3 17.1 1 17.7 7 17.6 6 27.0 0 N N 15 5 14 4 15 5 15 5 15 5 15 5 15 5 15 5 15 5 14 4 15 5 15 5 15 5 15 5 15 5 15 5 10 0 5 5 15 5 15 5 15 5 15 5 11 1 15 5 Contro o Mean n 80.6 6 72.6 6 81.1 1 73.9 9 82.2 2 71.7 7 32.6 6 12.2 2 17.8 8 7.1 1 20.0 0 11.1 1 8.9 9 17.8 8 2.2 2 85.6 6 71.7 7 40.0 0 55.6 6 19.3 3 18.7 7 19.3 3 8.2 2 2.2 2 SD D 13.6 6 23.2 2 19.8 8 19.1 1 17.2 2 14.7 7 22.8 8 17.2 2 20.4 4 14.2 2 27.6 6 20.6 6 19.8 8 24.8 8 8.6 6 17.7 7 13.7 7 27.9 9 24.1 1 14.8 8 11.9 9 17.6 6 5.3 3 8.6 6
