Annals of Surgical Oncology 14(3):1105–1113
DOI: 10.1245/s10434-006-9304-5
Monitoring Health Outcomes Following Cytoreductive Surgery Plus Intraperitoneal Hyperthermic Chemotherapy for Peritoneal Carcinomatosis Richard P. McQuellon,1,4 Suzanne C. Danhauer,1,4 Gregory B. Russell,2,4 Perry Shen,3,4 Joyce Fenstermaker,3 John H. Stewart,3,4 and Edward A. Levine3,4
1
Department of Internal Medicine, Section of Hematology and Oncology, Wake Forest University, School of Medicine, Winston-Salem, NC, USA 2 Department of Biostatistics, Wake Forest University, School of Medicine, Winston-Salem, NC, USA 3 Department of Surgical Oncology, Wake Forest University, School of Medicine, Winston-Salem, NC, USA 4 Comprehensive Cancer Center of Wake Forest University, Medical Center Blvd., Winston-Salem, NC 27157-1082, USA
Background: Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for peritoneal carcinomitosis (PC) is an aggressive treatment designed to alleviate symptoms and prolong life. It is associated with physical and psychological morbidity. The purpose of this study was to monitor health outcomes related to treatment. Methods: Patients completed a questionnaire before and after surgery at 3, 6 and 12 months. The questionnaire consisted of basic demographic items as well as the Functional Assessment of Cancer Therapy–Colon Scale (FACT-C), SF-36 Medical Outcomes Study Health Survey, Center for Epidemiologic Studies–Depression Scale (CES-D), Brief Pain Inventory–Short Form, and ECOG Performance Status Rating. Time trends were assessed with mixed models (SAS PROC MIXED) so as to use all data and to account for missing data. Results: Ninety-six patients (49% females, 9% African Americans) of an average age of 52.9 (SD = 12.5) years were assessed before surgery. PC originated in primary lesions of the appendix (n = 36); colon/rectum (n = 24); mesothelium (n = 9); ovary (n = 5); stomach (n = 4); and miscellaneous (n = 18). Quality of life (QOL) and pain scores improved from baseline to 12 months. Physical functioning changed over the 12-month study period with improvement recorded at 6 months. The percentage of patients reporting significant depressive symptom at each time point was; baseline= 32%; 3 months= 19%; 6 & 12 months= 24%. Conclusions: Acceptable QOL, return of functional status, and reduced pain can be attained between 3 and 6 months following treatment although some deficits in general health remain. Depressive symptoms are common and should be monitored. Key Words: Health outcomes—Intraperitoneal hyperthermic chemotherapy (IPHC).
Cytoreductive surgery followed by IPHC for peritoneal carcinomatosis is an intensive treatment designed to alleviate symptoms and prolong life. It is
often the treatment of last resort for patients who are diagnosed with an advanced disease or where other treatment courses have failed.1,2 Systematic monitoring of health outcomes in this setting has become more important due to increasing emphasis on quality as well as quantity of life. There are several reasons for this shift. First, there has been an exponential increase of information available through the Internet. Consumers of health care can now evaluate
Received February 21, 2006; accepted July 21, 2006; published online January 6, 2007. Address correspondence and reprint requests to: Richard P. McQuellon; E-mail:
[email protected] Published by Springer Science+Business Media, Inc. 2007 The Society of Surgical Oncology, Inc.
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the effectiveness of potential treatments at the same time as practitioners. Furthermore, data on patientrated outcomes and quality of life (QOL) are now more prominent in the literature, even though systematic investigation in these areas outside of clinical trials is rare. Second, the behavioral sciences have developed assessment questionnaires that provide valid and reliable measurement of patient-rated outcomes. Several such instruments, i.e., the Functional Assessment of Cancer Therapy (FACT) and the European Organization Research and Treatment Cancer (EORTC) questionnaires have been used in hundreds of clinical trials over the past decade.3,4 Finally, QOL and patient-rated outcomes can be used to predict medical outcomes as well as inform patients trying to decide on which type of treatment to undergo for their cancer. We have described patient-rated outcomes and QOL previously in IPHC patients.5,6 In one study we reported on QOL outcomes prior to cytoreductive surgery plus IPHC and at post-surgery and 3, 6 and 12 months.5 There was a significant change over time on several of the FACT subscales and on overall QOL as measured by the FACT-C, with a general pattern of decline in scores at 3 months and return to baseline at 6 months. Patients with ascites at baseline reported a poorer QOL relative to those without ascites. Following the cytoreductive surgery and IPHC treatment, overall QOL scores were reversed for patients with and without ascites. Thus, symptom relief was reported as a major positive effect of treatment just following surgery. In general, overall QOL trends down and has been reported as declining immediately following cytoreductive surgery plus IPHC. Similar findings have been reported elsewhere.7 In summary, we prospectively studied and systematically monitored patient-rated health outcomes (QOL, physical functioning, depression and pain) before and after cytoreductive surgery plus IPHC in patients with life threatening illness and few treatment options other than best supportive care.
PATIENTS AND METHODS Eligibility All consecutively treated patients at the Comprehensive Cancer Center of Wake Forest University between January 1, 1998 through January 31, 2005 were eligible for the study. Patients were required to have normal organ function (serum creatinine Ann. Surg. Oncol. Vol. 14, No. 3, 2007
<2 mg/dl or creatinine clearance 60 ml/min; alkaline phosphatase, and SGOT (AST) or SGPT (ALT) <3· upper limit of normal; white blood count 4,000/mm3, platelet count 100,000/mm3). Additionally, patients had to be English speaking, had no significant psychiatric history, be 18 years of age or older, not pregnant, and be able to comprehend the study procedure and objectives. Patients were not eligible if they had uncontrolled or severe cardiovascular disease, including recent (<3 months) myocardial infarction, congestive heart failure, angina (symptomatic despite optimal medical management), or uncontrolled hypertension. Patients were also ineligible if they had active bacterial, viral, or fungal infection, active peptic ulcer disease, uncontrolled diabetes mellitus, or severe obstructive or restrictive pulmonary disease. Patients with parenchymal liver metastatic disease or lung metastases were excluded. All study participants signed a formal consent form meeting institutional, state and federal guidelines. This study was approved by the Wake Forest University Health Sciences Institutional Review Board and met all requirements and guidelines of local and national governmental agencies. On the date that the patients were evaluated for IPHC, they were invited to participate in the QOL part of the study. They were informed that prior to surgery and at four subsequent time points following treatment they would be asked to complete study questionnaires. Patients were interviewed in person at baseline and asked to complete a packet of questionnaires. At approximately 3, 6, 12 and 24 months post-surgery, patients were mailed questionnaire packets. (Only data recorded through the first 12 months are reported here). These packets included all instruments administered at baseline and at postsurgery follow-up. Patients were told to return the questionnaires in a self-addressed, stamped envelope. Follow-up phone calls were made to patients who did not return the questionnaires within approximately 2 weeks. Surgery and IPHC Procedure All patients underwent cytoreductive surgery followed by IPHC. This procedure has been described in detail elsewhere.8 Following cytoreductive surgery, tubes were placed in the abdomen to allow for the circulation of fluid (typically 3 l) and heated (40.0C) mitomycin C through the abdominal cavity for 2 h. Following the perfusion, patients were transferred to the intensive care unit for follow-up care.
MONITORING HEALTH OUTCOMES FOLLOWING IPHC
Questionnaires The Functional Assessment of Cancer Therapy—Colon Scale (FACT-C)3 The general version of the Functional Assessment of Cancer Therapy (FACT-G) is a 27-item self-report questionnaire that measures QOL in cancer patients. The FACT-C is the FACT-G plus the 9-item colon subscale. We chose the colon subscale because it includes items that best address symptoms associated with peritoneal carcinometosis (PC) and there is currently no FACT subscale specifically designed for PC patients. The FACT consists of four subscales measuring physical (PWB), functional (FWB), social/family (SFWB), emotional well-being (EWB). A trial outcome index (TOI) representing PWB + FWB + the C subscale was used as a measure of treatment impact on physical symptoms and functioning. The FACT can be either self-administered or used in an interview format and is easily completed in 5-10 min. Patients are asked to rate themselves on how they feel today and over the past 7 days on a Likert scale from 0 (not at all) to 4 (very much). The FACT-G provides subscale scores and a total QOL score. A higher score indicates better QOL. CronbachÕs Alpha for each subscale has been reported as follows: PWB (0.82); FWB (0.80); SFWB (0.69); EWB (0.74); and total FACT-G (0.89). The Medical Outcomes Study Health Survey, Short Form (SF-36)9,10 The SF-36 is a 36-item generic health measure that assesses eight areas of perceived health: physical functioning (PF), role-physical (RP), role-emotional (RE), bodily pain (BP), general health (GH), vitality (V), social functioning (SF), and mental health (MH). For PF, the patient is asked to rate the degree to which ten activities (vigorous activity, moderate activity, lifting and carrying groceries, walking several flights of stairs, walking one flight of stairs, bending and kneeling or stooping, walking greater than a mile, walking several blocks, walking one block, bathing and dressing) are limited on a scale with three possible descriptors (not limited, limited a little and limited a lot). A higher score indicates better functioning. Standardized scores range from 0 to 100 and have been reported on a variety of different patient populations. The Brief Pain Inventory—Short Form (BPI)11 The BPI is a 14-item, self-report instrument designed to assess pain in cancer patients and persons with other diseases. The BPI measures both the
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intensity of pain (sensory dimension, six items plus one item regarding current medications) and interference of pain in the patientÕs life (reactive dimension, seven items). Since pain may be a likely outcome of aggressive treatment and/or disease progression, it is a particularly important area to measure in this patient population. Patients were asked to report on their pain level over the past 7 days. The Center for Epidemiologic Studies–Depression Scale (CES-D)12 The CES-D is a 20-item self-report measure developed to screen for depressive disorders. It has high sensitivity and positive predictive value for detecting depressive disorders (major depression and dysthymia). Cut-off scores indicate the likelihood that a subject meets DSM-IV criteria for the diagnosis of depression. A score of ‡16 or 17 has been used as the cutoff score with higher scores indicating significant depressive symptoms.12–14 We used the more conservative cutoff score of ‡17 here. The Eastern Cooperative Oncology Group (ECOG) Performance Status Rating Scale15 This is a single item rating of activity level where 0 = fully ambulatory without symptoms; 1 = fully ambulatory with symptoms; 2 = requiring bed rest (or equivalent) less than 50% of the waking day; 3 = requiring bed rest (or equivalent) greater than 50% of the waking day; and 4 = bedridden. Patients rated their current activity level. Sociodemographic Information and Additional Items Standard sociodemographic information (age, gender, race, marital status, etc.) was collected. Additional questions were asked, especially about physical appearance and activity level since many patients entered treatment with malignant ascites, a condition that often changes physical appearance and functional status dramatically. In summary, the main outcomes of interest in this study were overall QOL, physical functioning, pain, and depressive symptoms. All questionnaires, with the exception of the ECOG performance rating scale, were keyed to the past 7 days so that patients rated the same period of time with each instrument.
Statistical Analysis Descriptive statistics, including means, standard deviations and ranges for continuous measures and frequencies and proportions for categorical variables,
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TABLE 1. Patient characteristics and demographic information
Total patients Mean age = 52.9 (SD = 12.5) (r = 27–80 years) Gender Female Male Race African American White Other Education 0–8 9–11 High school Some college Jr. college College/postgraduate Advanced degree Unknown Marital status Married Single Separated/divorced Widowed Diagnosis Appendix Colon/rectum Mesothelioma Ovary Stomach Miscellaneous
Number
Percentage
96
100
point. Twenty patients were either too sick or declined to participate. One patient was lost to followup. Quality of Life—The FACT and SF-36 Health Survey
47 49
49 51
9 86 1
9 90 1
3 7 29 16 5 22 9 (Missing 5)
3 8 32 18 6 24 9
77 6 8 4
81 6 8 4
36 24 9 5 4 18
38 25 9 5 4 19
were calculated. To assess the effect of time on the outcome measures, repeated measures utilizing mixed models (SAS PROC MIXED) were fit for each of the dependent measures. The mixed approach allows for analyses of incomplete or missing data while also accounting for correlation within individuals. P values less than 0.05 were considered to be significant; measures that were observed to have changed significantly over time (baseline to 12 months) are reported.
The results of the FACT QOL measure are reported in Table 2. All values are arithmetic mean scores. Statistically significant changes over time (baseline to 12 months) were recorded for all subscales, and the overall score with the exception of the social/family well-being subscale which remained consistently high throughout the study period. FACT-G mean scores at baseline and 3 months are similar to the score of approximately 80.0 which has been reported as the norm for a sample from the general US adult population.16 These results must be interpreted cautiously since there is a considerable attrition from baseline to 12 months. However, the method of analysis used adjusts for missing data, resulting in a reliable estimate of values at all time points. All subscales with the exception of physical well-being returned to baseline levels by 3 months for the 38 patients who completed their QOL surveys at that time. Mean scores (SD) for the SF-36 are reported in Table 3. There was a significant overall effect from baseline to 12 months for the PF, RF, BP subscales and borderline significance for SF and MH. Trends in the scores can be seen in Fig. 1. There has been some anecdotal evidence that appendiceal cancer patients may present with less extensive disease and consequently rate their QOL higher than all other diagnostic categories at baseline and throughout the course of their disease. We conducted post hoc t tests comparing appendiceal cancer patients (n = 33) with gastric and colorectal cancer patients (n = 26) at baseline. There were no statistically significant differences on the following patientrated outcomes: the FACT and its subscales, the CES-D, and performance status.
RESULTS Patient characteristics are described in Table 1. A total of 96 patients were enrolled in the study at baseline. A total of 24 patients completed the FACTC at 12 months. Thirty-one patients with the following diagnoses were deceased: gastric (n = 4), colorectal (n = 7), appendix (n = 9), adrenal (n = 1), mesothelioma (n = 3), ovarian (n = 2), small bowel (n = 2), GI stromal tumor (n = 1), and primary PC (n = 2). Twenty-one patients had not reached the 12 months post-baseline assessment Ann. Surg. Oncol. Vol. 14, No. 3, 2007
Depressive Symptoms and Pain Mean scores (SD) on the CES-D were the following: baseline [n = 95, 13.8 (9.6)], 3 months [n = 39, 11.5 (7.8)], 6 months [n = 32, 10.3 (7.4)], and 1 year [n = 26, 10.6 (9.1)]. Change over the 1-year period in the CES-D is significant (P = 0.024), indicating less depression. The number of patients who scored 17 or greater (placing them in the category of possibly depressed and in need of further screening) was as follows: baseline, n = 30 (32%); 3 months, n = 7
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MONITORING HEALTH OUTCOMES FOLLOWING IPHC
TABLE 2. Functional assessment of cancer therapy-colon (FACT-C) mean scores at four time points and overall test of significance Mean (SD) Baseline (n = 96) PWB SFWB EWB FWB Colon sub FACT-G FACT-C TOI
21.0 23.9 16.0 17.9 22.1 78.9 101.0 61.1
Mean (SD)
3 months (n = 38)
(6.1) (4.1) (5.1) (5.7) (5.4) (14.6) (18.2) (14.8)
19.6 23.1 18.9 18.4 23.2 80.0 103.2 61.2
6 months (n = 32)
(6.0) (3.7) (3.4) (5.5) (5.6) (13.3) (17.1) (14.2)
23.3 23.0 17.8 20.8 24.4 84.9 109.3 68.5
12 months (n = 24)
(4.2) (3.9) (4.0) (5.6) (4.1) (13.2) (16.0) (10.9)
23.2 23.7 17.8 20.4 25.5 85.5 111.1 69.1
(3.7) (3.9) (4.0) (4.9) (3.8) (11.5) (13.1) (9.2)
P value 0.018 0.27 0.0001 0.045 0.012 0.017 0.008 0.011
PWB, physical well-being; SFWB, social/family well-being; EWB, emotional well-being; FWB, functional well-being; Colon sub, colon subscale; FACT-G; FACT-General; FACT-C; FACT-Colon; TOI, treatment outcome index.
TABLE 3. Medical Outcomes Study Health Survey (SF-36) mean scores at four time points and overall test of significance Mean (SD) Baseline (n = 95) PF RP BP GH VT SF RE MH
69.5 36.3 64.8 55.6 58.1 51.2 67.4 61.3
(27.5) (42.6) (26.7) (15.6) (10.4) (14.3) (42.1) (9.6)
Mean (SD)
3 months (n = 38) 53.9 24.3 62.9 56.3 63.1 51.5 74.5 64.8
6 months (n = 32)
(27.8) (37.3) (27.6) (16.4) (13.9) (10.1) (35.8) (7.9)
80.0 54.0 82.8 52.7 58.1 56.4 75.3 65.3
(17.4) (45.2) (17.5) (14.5) (10.6) (13.8) (38.5) (8.0)
12 months (n = 24) 71.0 53.0 81.5 52.2 56.8 44.0 70.7 61.4
(25.0) (45.3) (20.1) (10.6) (7.3) (13.6) (41.7) (6.7)
P value 0.0006 0.016 0.0007 0.37 0.065 0.055 0.71 0.055
PF, physical functioning; RP, role physical; BP, bodily pain; GH, general health; VT, vitality; SF, social functioning; RE, role emotional; MH, mental health.
100 90 80 70 60 50 40 30 20 10 0
Baseline 3 Months 6 Months
un
ol e
ct io ni P h ng Bo ysic a G dily l en Pa er in al H ea So lt cia Vi h lF ta li u R nct ty ol e ion Em in g o M en tion ta a lH l ea lth
12 Months
R
al F ic ys Ph
(19%); 6 months, n = 8 (24%), and 1 year, n = 6 (24%). Mean pain scores for worst and least pain recorded at baseline, 3 months, 6 months and 1 year are reported in Fig. 2. Total pain interference mean scores are reported in Fig. 3. Pain at its worst changes toward the better from baseline through 12 months (P = 0.038). We also recorded the number and percentages of people who scored in the lower (rating = 1, 2 or 3) and upper ranges (rating = 8, 9 and 10) for ‘‘worst’’ and ‘‘least’’ pain. Prior to surgery, 51 (54%) of the 95 patients rated their pain between 1 and 3 on a 10-point Likert scale where 1 equals no pain and 10 equals worst possible pain. Sixteen patients (17%) rated their pain between 8 and 10 prior to surgery. At approximately 3 months following surgery, pain ratings were as follows: 1–3, n = 21 (57%); 8–10, n = 3 (8%). The percentage of patients reporting relatively intense pain (rated 8–10) decreased by more than half from 17 to 8% at the postsurgery assessment. Those patients who reported very little pain (rated 1–3) rose slightly from 54 to 57%.
FIG. 1. SF-36 Health Survey mean scores (SD) at baseline, 3, 6 and 12 months.
Performance Status, Functional Status and ‘‘Returning to Normal’’ Patient-rated performance status is reported in Table 4. Self-rated mean score (SD) on returning to 100% of normal activities at 3, 6, and 12 months, respectively, was as follows: 60.7 (26.4); 80.5 (24.2); Ann. Surg. Oncol. Vol. 14, No. 3, 2007
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5.0 4.5
Reported Pain
4.0 3.5 3.0 2.5
Worst Pain
2.0
Least Pain
1.5 1.0 0.5 0.0 Baseline
3 Months
6 Months
12 Months
Assessment 1
Assessment 2
Assessment 3
Assessment 4
FIG. 2. Measure of least and worst pain from brief pain inventory (BPI).
Level of Interference
4.0 3.5 General Activity Mood
3.0 2.5
Walking Ability Normal Work
2.0 1.5
Relations Sleep Pain
1.0
Enjoyment
0.5 0.0 Baseline
3 Months
6 Months
12 Months
Assessment 1
Assessment 2
Assessment 3
Assessment 4
FIG. 3. Measure of interference of pain according to brief inventory of pain (BPI).
80.8 (23.0). Responses to specific items on the PF subscale are reported in Table 5. Nearly in every item (with the exception of bending, kneeling or stooping) patients reported the following general pattern: an increase of limitations at 3 months post baseline, and then a decrease in limitations at 12 months to baseline levels for most patients. Table 5 includes patient ratings of their general self-rated health compared to 1 year ago at four additional time points.
DISCUSSION In summary, for the patients remaining in the sample, the mean FACT-G (overall QOL) score improved from baseline to 12 months. Improvement in the FACT-TOI, an index of treatment outcome, indicates successful symptom management following IPHC. Physical well-being changed over the 12month study period with improvement recorded at 6 months where patients reported returning to 80% of their normal activities. Approximately, 20% of patients reported significant depressive symptoms Ann. Surg. Oncol. Vol. 14, No. 3, 2007
during the first year after IPHC. These results may reflect the best possible outcome given that study dropouts may have compromised QOL due to recurrence or complications. A slightly different pattern emerges when comparing the overall QOL as measured by the FACT and the SF-36. At 3 months, the overall QOL score of 80.0 on the FACT is similar to that reported for the US general population.16 However, on the Physical Functioning Subscale of the SF-36, a significant percentage of patients report themselves as ‘‘limited a lot’’ on specific items. For example, with regard to vigorous activity such as running, 71% (n = 24) of patients rated themselves as limited a lot at 3 months, compared to 51% (n = 48) at baseline. A closer examination of the items may help explain this apparent discrepancy. This discrepancy suggests that on the one hand overall QOL returns to near normal at 3 months (the FACT-G) whereas on the other hand, there are a significant percentage of patients that reported limitations on physical functioning (SF36). Closer examination of the FACT items may provide a clearer understanding. Specifically, the items on the physical well-being subscale of the FACT are more focused on symptoms, e.g. nausea, pain, feeling ill or lack of energy. The SF-36 items provide a more detailed look at activities that may or may not impair a personÕs rating of their overall QOL as measured by the four FACT subscales. Thus, it is true that patients can report limitations on specific activities at 3 months while at the same time, collectively, reaching a score on overall QOL that is similar to the general adult population. The FACT is disease specific and measures the presence/absence of cancer/ disease while the SF-36 measures the presence of physical and emotional health. Thus, it is possible that patients may approach the US population norms on the overall FACT score while at the same time have scores on the SF-36 that are considerably lower than the population norms for the SF-36. The pattern and meaning of the SF-36 scores over the four assessment time points from baseline through 12 months is more apparent as illustrated in Fig. 1. and when compared to US population norms.9 Mean scores on the Physical Functioning and Role Physical subscales show considerable decline from baseline to 3 months and then rebound at 6 months where both subscales achieve their highest scores. Nevertheless, the highest mean score (SD) achieved at any time point was 80.0 (17.4) for Physical Functioning and 54.0 (45.2) for the Role Physical subscale. In contrast, the mean score for the general US population between the ages of 45 and 54 is 84.6
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TABLE 4. Patient performance status rating (PSR) n (%) PSR 0 1 2 3 4
a
Baseline ( n = 95) 54 23 12 6 0
n (%) 3 months (n = 38)
(57) (24) (13) (6)
8 20 8 2 0
6 months (n = 32)
12 months (n = 24)
17 (53) 13 (44) 1 (3) 0 0
14 (58) 8 (33) 2 (9) 0 0
(23) (51) (21) (5)
Ratings were made by patients who were asked to place themselves in one of the following categories: 0 = I have normal activity; 1 = I have some symptoms, but I can walk and I do not spend any extra time in bed; 2 = I need some time in bed, but it is less than 50% of normal daytime; 3 = I need to be in bed greater than 50% of normal daytime; 4 = I am unable to get out of bed. a Numbers differ slightly; n = 1 rating is missing.
TABLE 5. Number (%) of patients who rated themselves as ‘‘limited a lot’’ on the SF-36 physical functioning subscale
Vigorous activities, such as running Moderate activities, such as playing golf Lifting/carrying groceries Climbing several flights of stairs Climbing one flight of stairs Bending, kneeling, or stooping Walking more than a mile Walking several blocks Walking one block Bath/dress yourself
N
Baseline
N
3-months
N
95 96 96 96 96 96 95 96 96 96
48 24 11 18 11 13 26 12 5 3
34 34 35 34 34 35 35 35 35 35
24 12 9 10 3 5 14 9 4 2
31 31 31 31 31 31 30 31 31 31
(51%) (25%) (11%) (19%) (3%) (14%) (27%) (13%) (5%) (3%)
(71%) (35%) (25%) (29%) (9%) (14%) (40%) (26%) (11%) (6%)
6-months 9 2 3 1 0 1 3 1 1 0
(29%) (6%) (10%) (3%) (0%) (3%) (10%) (3%) (3%) (0%)
N 25 24 24 25 25 25 25 25 25 25
12-months 12 6 2 3 1 1 5 4 2 1
(48%) (25%) (8%) (12%) (4%) (4%) (20%) (16%) (8%) (4%)
TABLE 6. Compared to a year ago, how would you rate your health in general now? n (%)
Much better/somewhat better Same Somewhat worse/much worse
n (%)
Baseline (n = 95)
3 months (n = 33)
6 months (n = 31)
12 months (n = 24)
19 (20) 23 (24) 53 (56)
14 (42) 4 (12) 15 (46)
18 (58) 5 (16) 8 (26)
16 (66) 4 (17) 4 (17)
on the Physical Functioning subscale and 82.6 on the Role Physical subscale. The bodily pain subscale score of 82.8 (17.5) is the only subscale that is considerably higher than the mean score reported for the general population of 73.1, suggesting even less pain in this patient population. Scores on the General Health subscale are remarkably consistent over the year of assessment ranging from a high of 56.3 (16.4) at 3 months to a low of 52.2 (10.6) at 12 months. However, the highest score achieved, 56.3, is still considerably lower than the 71.8 mean score reported for the general population. This may be due to the nature of the items on this scale which include: ‘‘I am as healthy as anybody I know’’ and ‘‘I expect my health to get worse.’’ Many patients understand that their disease is not curable and therefore would answer accordingly, lowering their general health score. The vitality subscale score of 63.1 (13.9) at 3 months
is very similar to the 61.8 score for the general population. The mean scores for the Social Functioning, Role Emotional, and Mental Health at 6 months are 56.4 (13.8), 75.3 (38.5), and 65.3 (8.0), respectively. These stand in contrast to the mean scores reported for the general population of 84.0, 83.6, and 75.3. On all subscales with the exception of general health and vitality, the highest mean scores are achieved at 6 months post-baseline assessment. Nevertheless, these scores with the exception of vitality are considerably lower than that which would be expected from the general US population of healthy adults. These patients must adapt to less than optimal health, relative to the general population over the course of the first year post-treatment. Several studies have utilized a prospective design and followed patients from baseline up to 1 year using the FACT and the SF-36. Alexander and colAnn. Surg. Oncol. Vol. 14, No. 3, 2007
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leagues prospectively examined 73 patients over 9 months with measurements at 6 weeks (n = 68), 3 months (n = 66), 6 months (n = 53) and 9 months (n = 45).7 They reported significantly improved scores from baseline to 3, 6, and 9 months. Overall FACT-C scores declined from baseline to 6 weeks, as might be expected in the immediate time period after surgery. In addition to the FACT scores, generic health related QOL was rated on the physical components scale (PCS) and the mental components scale (MCS) of the SF-36. MCS increased significantly at 6 weeks and 3 months but did not differ at 6 and 9 months relative to baseline. The physical component subscale declined at 6 weeks as might be expected. Additional studies have examined long-term functioning in patients following cytoreductive surgery plus IPHC. Schmidt and colleagues surveyed 20 patients with an average post-treatment time of 4 years (range 1–8 years).17 The authors compared these patients on EORTC quality of life questionnaire (QLQ-C30) with the general Norwegian population. Global health as rated by IPHC patients was not significantly different than that in the control population. However, there were differences in several other subscales including physical functioning, role functioning, social functioning, fatigue, nausea/ vomiting, constipation/diarrhea, all favoring the control population. Thus, there is some reported morbidity which appears to linger. However, patients did rate their overall global health as similar to that of the general patient population, differing from our findings. Mean scores from baseline to 12 months on the CES-D show significant improvement in depressive symptomatology in this group of patients (P = 0.045). However, mean scores can mask considerable individual variability. In other words, while the mean group score is less than the selected clinical cut-off score at 12 months, 24% of the sample indicated significant depressive symptomatology at that time. As a group, for those patients who continue in the study, it appears that depressive symptomatology does diminish. It is logical that patients under great duress at the diagnosis and initiation of treatment would likely have significant existential concerns and distress over the prospect of no cure for their disease. It may be that those patients with the most significant symptomatology drop out of the study due to illness or death and therefore are under-represented at the 12-month evaluation point. This group would presumably be highly distressed and likely express depressive symptoms, thus increasing the mean CESAnn. Surg. Oncol. Vol. 14, No. 3, 2007
D scores. For this reason, we also categorized the patients using the CES-D cut score of ‡17. The range of patients reporting significant depressive symptoms at least one time during the four measurement periods ranged from 19 to 32%. This percentage is not surprising since the cytoreductive surgery and IPHC procedure are taxing on the most resilient of patients and families. Further, many of the patients will experience recurrence in the first 2 years after IPHC. Some depressive symptomatology may represent the physical symptoms that are measured by a number of items on the CES-D, e.g. poor appetite, everything I did was an effort, sleep restless, and could not get going. Without further screening, it is impossible to know to what extent such symptoms represent evidence of true depressive symptoms rather than somatic problems directly related to treatment or disease. Further assessment is needed with each patient in order to detect to what extent these symptoms are driven by psychological distress. This finding suggests that IPHC patients could benefit from evaluation for depression and possibly more intense psychological care. We have begun a screening procedure whereby all patients who score 17 or greater are called for further evaluation by the IPHC psychologist. Interpretation of the BPI must be done cautiously, since we did not systematically track exactly how patients were utilizing pain medications. Also, mean scores reported on the BPI were considerably lower than the cut-off scores of 4 for pain severity and 7 for pain interference indicative of clinical significance. Nevertheless, there is a trend towards reduced reported worst pain over the course of the study and a reduction in the degree of interference that pain plays for patients from baseline to 12 months. In this patient population, pain appears to be well managed. The percentage of patients who rate their general health as much/somewhat better compared to a year ago changes considerably over the course of the study. Not unexpectedly, at baseline, only 20% of patients report that their health is better when compared to 1 year earlier whereas at 12 months, the percentage increases dramatically to 66%. A common concern that patients have is when they might return to normal. For patients receiving cytoreductive surgery plus IPHC, the question itself represents a recent and dramatic change in philosophy. Many of these patients have been told that there is no treatment for their situation and that they should ‘‘go home and get their affairs in order.’’ The idea of telling this group of patients that they would return to normal was simply inconceivable prior to the ad-
MONITORING HEALTH OUTCOMES FOLLOWING IPHC
vent of cytoreductive surgery followed by IPHC. However, with the successes reported in this type of treatment and the long-term survivors reported,2,6 a return to normal function is a real possibility. In our study population, as early as 3 and 6 months postbaseline, patients reported returning to 60 and 80% of normal activities, respectively. It appears that the FACT and SF-36 QOL data as well as patient responses to an item regarding returning to normal suggest that surviving patients can expect to return to a reasonable level of functioning between 3 and 6 months following this type of surgery. Of course, this generalization has many exceptions with some patients returning to normal more quickly and others taking much longer, if ever, to regain a life of normal quality. Quality of life and patient-rated outcomes are key factors in the assessment of cytoreductive surgery and IPHC for peritoneal surface disease. Overall QOL declines in the first few months after surgery, but generally improves over the course of the first year, and is significantly better than QOL recorded at baseline. However, patients are still likely to experience general health that is compromised relative to their peers as represented in national normative scores on the SF-36. Also, depressive symptomatology develops in approximately one quarter of survivors over the course of the first year after IPHC. It is likely that dropouts have significant psychosocial difficulties. An area for future research is the group of patients who dropped out of the study and may have QOL and psychosocial problems associated with recurrence and those patients with significant depressive symptoms.
ACKNOWLEDGEMENTS This study was supported in part by the Robert Welborne Fund. The authors gratefully acknowledge the assistance of Tammy Alley, Adrienne Robbins, Daniel Burke and the courage and thoughtfulness of the patients and family members who participated in this study.
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