Comparison of the quality of life of early and advanced stage ovarian cancer survivors

Gynecologic Oncology 114 (2009) 353–359

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Gynecologic Oncology j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / y g y n o

Comparison of the quality of life of early and advanced stage ovarian cancer survivors☆ Kristina L. Mirabeau-Beale a,⁎, Alice B. Kornblith b, Richard T. Penson c, Hang Lee a,d, Annekathryn Goodman e, Susana M. Campos f, Linda Duska g, Lauren Pereira f, Jessica Bryan f, Ursula A. Matulonis f a

Harvard Medical School, 25 Shattuck Street, Boston, MA, USA Division of Women's Cancers, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA, USA Department of Hematology and Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, USA d Biostatistics Center at Massachusetts General Hospital, 55 Fruit Street, Boston, MA, USA e Division of Gynecologic Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, USA f Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA, USA g Division of Gynecologic Oncology, University of Virginia Health Systems, PO Box 800712, Charlottesville, VA 22908, USA b c

a r t i c l e

i n f o

Article history: Received 12 January 2009 Available online 28 May 2009 Keywords: Ovarian cancer Quality of life Survivorship Fear of recurrence

a b s t r a c t Objective. The objective of this study was to compare the long-term adjustment and QOL of early and advanced stage ovarian cancer survivors (OCS). Methods. Early and advanced OCS N 3 years from diagnosis with no evidence of recurrent cancer were interviewed. The following surveys were administered: EORTC QLQ-C30 (overall QOL) and QLQ-OV28 (ovarian specific issues), MHI-17 (anxiety, depression and global well-being), CALGB sexual functioning, FACT Fatigue, Beck's Hopelessness Scale, Fear of Recurrence (FOR), PCL-C post-traumatic stress disorder (PTSD), Unmet Needs, FACT-Spirituality (FACT-Sp), complementary therapy (CAM use), and MOS Social Support Survey (MOS). The results of the surveys were compared between the early and advanced stage groups. Results. 42 advanced and 58 early stage patients were interviewed. The majority of survivors scored above the medical outpatient norm for emotional status (71% of early stage and 64% of advanced stage survivors). Overall QOL, fatigue, hopelessness, spirituality, social support, degree to which unmet needs were met and use of complementary therapy, did not differ between the two groups. No advanced stage OCS had diagnosable PTSD scores, while 6.9% of early stage survivors had scores indicative of PTSD. Decreased sexual interest attributed to cancer and anxiety when getting CA-125 testing were of concern for both groups. OCS used on average 5 CAM to improve their QOL. Conclusion. Regardless of staging, OCS experience similarly overall positive QOL and adjustment, though PTSD, sexual problems and fear of recurrence are still important for some survivors. © 2009 Elsevier Inc. All rights reserved.

Introduction Approximately, 22,000 new cases of ovarian cancer were diagnosed in 2008, and the majority of patients were diagnosed with advanced stage [1]. Significant survival differences exist between early stage (FIGO I and II) and advanced stage (III and IV) ovarian cancer. Five year survival is estimated to be N70% for early stage patients, compared to 10–15% for advanced stage patients. Moreover, most women with advanced cancer will relapse with disease that is more resistant to chemotherapy [2]. These discrepancies in prognosis and survival may have implications for the quality of life (QOL) and emotional status of survivors.

☆ Presented at ASCO 2008 annual meeting GYN poster session on 5/31/08. ⁎ Corresponding author. 170 Brookline Ave, Unit 829, Boston, MA 02115, USA. E-mail address: [email protected] (K.L. Mirabeau-Beale). 0090-8258/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2009.05.009

Studies to date examining quality of life in ovarian cancer survivors (OCS) who are currently disease-free have primarily focused on early stage survivors, and found overall QOL ranging from good to excellent [3] with generally positive adjustment [4,5]. To our knowledge this is the first study to directly compare QOL and long-term physical, mental, and sexual functions between early and advanced stage survivors of ovarian cancer who are more than 3 years from diagnosis and are free of cancer recurrence. The measures we selected to assess these differences were chosen because they could be grouped into outcome measures and modifying variables that have been previously validated in the survivorship literature as having a direct impact on survivor QOL and adjustment. For example, we believe worse physical side effects would be a predictor of poor long-term adjustment and would differ between early and advanced survivors. Our hypothesis was that advanced survivors would have a worse QOL and long-term adjustment because their fear of recurrence (FOR) would be greater than that of early staged survivors.

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Patients and methods Study design and eligibility English-speaking ovarian cancer survivors were identified from the patient logs at the Dana-Farber Cancer Institute (DFCI), Brigham and Women's Hospital (BWH), or the Massachusetts General Hospital (MGH), all in Boston, MA. Eligibility was confirmed by the gynecologic oncologist, medical oncologist, and/or nurse practitioner. Subjects were eligible if the following criteria were met: 1) a diagnosis of either FIGO stage I, II, III, or IV surgically staged, epithelial ovarian, fallopian tube, or primary peritoneal cancer and 2) at least 3 years following the diagnosis of cancer with no evidence of cancer recurrence. Survivors with a prior, concurrent, or subsequent history of a second primary non-metastatic cancer were eligible if the treatment of this malignancy did not require hormonal, chemotherapy or radiation therapy. Survivors were contacted by mail or during routine clinic visits and asked whether they were interested in participating. Subjects expressing study interest or who had not responded in 2 weeks were contacted by phone by the Research Interviewer. Consenting subjects were given a copy of the Dana-Farber/Harvard Cancer Center IRB-approved consent form along with a copy of the survey questions. An interview was subsequently conducted either in person or over the phone, after scheduling a mutually agreed upon time. The first 5 patients in each cohort served as the feasibility phase, and patients were asked whether any of the questions were difficult to understand, whether any of the questions upset them or made them feel uncomfortable, whether the questionnaires left out anything important to ask concerning cancer survivorship, and whether the interview was too long. The results of this pilot assessment confirmed that our selection of instruments effectively encompassed the breadth of factors implicated in survivors QOL from the patients perspective and that the survey length was manageable. Most interviews lasted

approximately 3 h, and no patients interviewed complained about the length of the interview or wished to stop in the middle due to fatigue. Moreover, patients received a copy of the survey ahead of time so that they had time to consider their responses before the live encounter with the interviewer during which all responses would be reviewed. A total of 118 early stage patients were asked to participate. Sixtyone subjects agreed to participate, and eventually 58 (49.2%) were interviewed; 3 subjects were not interviewed because of scheduling conflicts on the part of the subjects. Eleven subjects responded that they did not wish to participate, and 46 subjects did not respond. Fiftyfour eligible advanced stage survivors were contacted, of whom 11 declined participation or did not respond. One patient was consented but could not be interviewed until after the study was closed. A total of 42 (77.8%) advanced stage survivors were eventually interviewed. Measures The telephone interview consisted of demographic information, as well as questions from the standardized instruments detailed below. Socio-demographic information Obtained at time of interview were: patient's current age and age at time of diagnosis, number and ages of household members and religious affiliation. Marital status, educational status, occupational status and household income at the time of diagnosis and at the time of interview were assessed. Subjects were asked whether they believed their current status was related to having had cancer. Type of treatment Use of chemotherapy, the number of cycles of chemotherapy, the specific chemotherapy drugs used, and the amount of time that had elapsed since initial diagnosis to the time of the interview was assessed by chart review. Subjects who received a carboplatin and paclitaxel combination, each received carboplatin AUC 5 and

Table 1 Survey instruments (patients and methods). Factor

Survey instrument (reference)

Socio-demographics

Assessed age of patient, marital status, educational status, occupational status and household income, all both at diagnosis and time of interview.

Scale

Chemotherapy Overall quality of life

Physical factors

1. EORTC QLQ-C30 + ovarian cancer module OV-28 [6,7] 2. Unmet needs of patient [8] 1. FACT/NTX (neurotoxicity) [9,10] 2. 3. 4. 5.

Psychological factors

FACT — fatigue [11–13] Sexual problems due to cancer (CALGB) [14] Menopausal symptoms (none) Comorbidities [15]

1. MHI-17 [16–20]

2. Beck's Hopelessness [21,22] 3. Fear of recurrence [23,24] 4. PCL-C (post traumatic stress disorder) [25,26] 5. FACT spirituality [27] Moderating factors

1. MOS social support [28] 2. Complementary therapy use [29]

48 items. Higher functioning scores = better functioning; Higher physical symptom scores = worse symptoms. 11 items. 3-point scale of the degree to which the need was unmet. 11 items. 5 point Likert scale, from ‘not at all’ (0) to ‘very much’ (4). Higher scores, more fatigue. 13 items. 5-point Likert scale from ‘not at all’ to ‘very much’ Higher scores, less fatigue. 6 items. Also assessed in EORTC OV28 ovarian cancer specific survey. 2 items. Higher scores, greater menopausal symptoms. 30 conditions where survivor rated on a 3 point Likert scale with higher scores, greater interference with activities. 17 items assessing anxiety, depression and positive affect. 6 point Likert scale ranging from ‘all of the time’ to ‘none of the time’. Higher MHI-Index total score and positive affect score, better mental health. Higher anxiety and depression scores, worse anxiety and depression. 20-items. True–false scale that yields a “hopelessness” score ranging from 0 to 20. Higher scores, greater hopelessness. 5 items. 5-point Likert scale ranging from 1 (strongly agree) to 5 (strongly disagree). Higher scores, greater fear. 17 items. Corresponding to DSM-IV PTSD. 5 point Likert scale 1 (not at all) to 5 (extremely). Higher scores, greater PTSD. Algorithm to calculate likely diagnosis of PTSD. 12 items. 5 point Likert scale ranging from 0 (not at all) to 4 (very much). High scores, greater spirituality. 20 items. 5 point Likert scale, ranging from ‘none of the time’ to ‘all of the time’. High scores = greater support. 40 items. Assessed whether pt used therapy to shrink tumor, improve QOL, or treat side effects.

K.L. Mirabeau-Beale et al. / Gynecologic Oncology 114 (2009) 353–359

paclitaxel 175 mg/m2 administered intravenously every 3 weeks according to the institutional guidelines of all three hospitals.

Table 3 Notable T-tests comparing early and advanced OCS. Variables

Survey instruments Table 1 summarizes the instruments used during the interviews, which were selected because they could be grouped into outcome measures and modifying variables that have been previously validated in survivorship literature as having direct impact on cancer survivors' QOL and adjustment (social, psychological, etc.). Statistical analysis Continuous outcomes are reported as means (+/− SD), and categorical outcomes are reported as frequency and proportion. Pearson's correlation coefficient was used to examine the linear associations of all quality of life subscales with age and age at diagnosis and time length

Table 2 Patient characteristics.

Age of patient Mean age at diagnosis Mean age at interview Age range at time of diagnosis Demographics White, non-Hispanic Other ethnicity Married College/advanced degree Work part or full-time Diagnosis Ovarian Fallopian tube Primary peritoneal Stage I II III IV Number of cycles of platinum-based chemotherapy 2 cycles 3 cycles 4 cycles 5 cycles 6 cycles 7 cycles 8 or 9 cycles (6 of which were platinum-based) ref. [34] N 10 cycles Type of chemotherapy received (n = 55) Carboplatin/paclitaxel Cisplatin/paclitaxel Cyclophosphamide/carboplatin Cyclophosphamide/cisplatin Triple doublets [ref. 30] Comorbidities Degenerative joint disease Hypertension Gastrointestinal distress Thyroid disease Psychological treatment Treatment or counseling for personal family problems Needed treatment for family/personal problems Needed prescription for medication for nerves

Early stage (n = 58)

Advanced stage (n = 42)

48.3 years (SD = 8.8) 55.7 years (SD = 9.4) 30–68 years

55.1 years (SD = 11.3) 61.2 years (SD = 11.0) 36–75 years

56 (97%) 2 (3%) 38 (66.7%) 38 (65.4%) 34 (58.6%)

38 (90.5%) 4 (9.5%) 26 (61.9%) 19 (45.2%) 23 (54.8%)

58 (100%) – –

34 (81%) 2 (4.7%) 6 (14.3%)

39 (67%) 19 (33%) – – (N = 55)

– – 19 (45%) 23 (55%) N = 42

1 1 12 1 33 3

2 25 1 11 3

47 2 2 1 3

26 2

18 (31%) 12 (21%) 10 (17%) 7 (12%)

18 (43.9%) 10 (23.8%) 11 (26.2) 8 (19.1%)

18 (31%)

8 (19.05%)

18 (31%)

13 (30.95)

19 (33%)

10 (23.81)

355

Age Early Adv Age at diagnosis Early Adv EORTC global Early Adv EORTC phys function Early Adv EORTC role function Early Adv EORTC emotional function Early Adv EORTC cognitive function Early Adv EORTC social function Early Adv MHI-17 global psych distress Early Adv MHI global well-being Early Adv MHI-17 index Early Adv CALGB # of sexual problems attributed to cancer Early Adv FACT — neurotoxicity Early Adv FACT — fatigue Early Adv Beck's Hopelessness Early Adv Fear of cancer recurrence Early Adv PTSD Early Adv PCL-C total Early Adv Degree of unmet needs Early Adv FACT — spirituality Early Adv MOS social support Early Adv CAMa use Early Adv CAM specifically to shrink tumor Early Adv CAM use to improve QOLb Early Adv

Mean

SD

Sig P = 0.0085

55.69 61.19

9.413 10.99

50 55.071

8.813 10.986

84.626 78.77

14.792 18.607

95.172 92.857

9.2438 9.2415

97.414 96.032

9.2621 8.8724

76.58 76.984

23.23 26.276

79.157 78.175

18.361 22.269

92.816 98.016

14.001 5.4628

15.575 19.008

14.698 18.472

72.552 68.286

17.579 19.384

77.728 74.23

12.495 15.555

1.7391 1.2903

1.9825 1.4188

34.779 34.171

5.379 5.2816

43.966 42.902

7.5416 8.723

2.5862 3.2857

2.734 3.9279

2.407 2.6655

0.7857 0.7457

0.2586 0. 2619

0.4417 0.445

6.89 0.0

8.5498 6.5042

1.3966 1.35

1.882 1.9289

38.613 37.69

8.002 7.9064

82.092 83.365

16.874 18.503

5.9138 5.5714

3.585 4.57

1.5536 1.5526

2.7891 2.0494

5.5536 5.2632

3.5261 3.8603

P = 0.0133

– NS

– NS

– NS

– NS

– NS

P = 0.0247

– NS

– NS

– NS

– NS

– NS

– NS

– NS

– NS

– NS

– NS

– NS

– NS

– NS

– NS

– NS

– NS

– NS: Results were not significant at a 5% significance level. a CAM: Complementary and alternative medicine. b QOL: Quality of life.

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Table 4 Pearson product moment correlations of QOL for early and advanced survivors. Variables Physical Side effects EORTC — fatigueb,c Early (n = 58) Advanced (n = 42) Nausea/vomitingb,c Early (n = 58) Advanced (n = 42) Painb,c Early (n = 58) Advanced (n = 42) Sleepb,c Early (n = 58) Advanced (n = 42) Abdominal symptoms Early (n = 58) Advanced (n = 42) FACT NTX (neurotoxicity)b Early (n = 58) Advanced (n = 41) FACT — fatiguea Early (n = 58) Advanced (n = 41) Function Physical functioninga,c Early (n = 58) Advanced (n = 42) Role functioninga,c Early (n = 58) Advanced (n = 42) Social functioninga,c Early (n = 58) Advanced (n = 42) Cognitive functioninga,c Early (n = 58) Advanced (n = 42) MOS social supporta Early (n = 58) Advanced (n = 42) Sexual problems Sexual problemsb Early (n = 46) Advanced (n = 31) Psychological factors MHI-17a Early (n = 58) Advanced (n = 42) Body imageb,c Early (n = 58) Advanced (n = 42) Emotional functioninga,c Early (n = 58) Advanced (n = 42) Beck's Hopelessnessb Early (n = 58) Advanced (n = 42) PCL-C total (PTSD)b,e Early (n = 58) Advanced (n = 42) FACT — faith–spiritualitya Early (n = 58) Advanced (n = 42) Fear of recurrenceb Early (n = 55) Advanced (n = 42) QOL Global QOLa Early (n = 58) Advanced (n = 42)

MHI-17a

EORTC overall QOLa

FACT faith/Spa

Fear of recurrenceb,d

r

r

r

R

− 0.57⁎⁎⁎⁎ .59⁎⁎⁎⁎

− 0.60⁎⁎⁎⁎ −0.59⁎⁎⁎⁎

− 0.41⁎⁎ − 0.36⁎

0.41⁎⁎ –

− 0.43⁎⁎⁎ –

− 0.45⁎⁎⁎ − 0.42⁎⁎

– –

– –

− 0.54⁎⁎⁎⁎ –

− 0.51⁎⁎⁎⁎ –

− 0.34⁎⁎ –

0.4⁎⁎ –

− 0.47⁎⁎⁎

− 0.36⁎⁎

− 0.35⁎⁎

0.30⁎

− 0.44⁎⁎⁎ –

− 0.46⁎⁎⁎ –

− 0.4⁎⁎ –

0.5⁎⁎⁎⁎ –

– –

– 0.35⁎

– –

– − 0.32⁎

0.61⁎⁎⁎⁎ 0.59⁎⁎⁎⁎

0.66⁎⁎⁎⁎ 0.59⁎⁎⁎⁎

0.41⁎⁎ –

− 0.55⁎⁎⁎⁎ –

– –

0.48⁎⁎⁎⁎ 0.55⁎⁎⁎⁎

0.47⁎⁎⁎ –

− 0.31⁎ –

.51⁎⁎⁎⁎ –

0.52⁎⁎⁎⁎ –

0.33⁎⁎ –

− 0.36⁎⁎ –

0.61⁎⁎⁎⁎ –

0.53⁎⁎⁎⁎ 0.41⁎⁎⁎

0.46⁎⁎⁎ –

− 0.57⁎⁎⁎⁎ − 0.36⁎

0.73⁎⁎⁎⁎ 0.75⁎⁎⁎⁎

0.72⁎⁎⁎⁎ 0.60⁎⁎⁎⁎

0.52⁎⁎⁎⁎ 0.59⁎⁎⁎⁎

0.59⁎⁎⁎⁎ − 0.33⁎

0.54⁎⁎⁎⁎ 0.64⁎⁎⁎⁎

0.41⁎⁎ 0.42⁎⁎

0.44⁎⁎⁎ 0.40⁎⁎

− 0.32⁎ − 0.34⁎

− 0.34⁎ –

– –

− 0.29⁎–

– –

1.0 1.0

0.70⁎⁎⁎⁎ 0.61⁎⁎⁎⁎

0.69⁎⁎⁎⁎ − 0.68⁎⁎⁎⁎

− 0.59⁎⁎⁎⁎ − 0.49⁎⁎⁎

− 0.45⁎⁎⁎ −0.45⁎⁎

− 0.41⁎⁎⁎ − 0.38⁎

− 0.32⁎⁎ − 0.39⁎⁎

0.5⁎⁎⁎⁎ 0.43⁎⁎

0.73⁎⁎⁎⁎ 0.75⁎⁎⁎⁎

0.69⁎⁎⁎⁎ 0.54⁎⁎⁎

0.50⁎⁎⁎⁎ 0.58⁎⁎⁎⁎

− 0.59⁎⁎⁎⁎ − 0.38⁎

− 0.60⁎⁎⁎⁎ −0.73⁎⁎⁎⁎

− 0.53⁎⁎⁎⁎ − 0.67⁎⁎⁎⁎

− 0.67⁎⁎⁎⁎ − 0.69⁎⁎⁎⁎

0.47⁎⁎⁎ 0.53⁎⁎⁎

− 0.76⁎⁎⁎⁎ − 0.73⁎⁎⁎⁎

− 0.80⁎⁎⁎⁎ − 0.43⁎⁎⁎

− 0.62⁎⁎⁎⁎ − 0.58⁎⁎⁎⁎

0.71⁎⁎⁎⁎ 0.48⁎⁎

0.69⁎⁎⁎⁎ − 0.68⁎⁎⁎⁎

0.56⁎⁎⁎⁎ 0.60⁎⁎⁎⁎

1.0 1.0

− 0.56⁎⁎⁎⁎ − 0.57⁎⁎⁎⁎

− 0.59⁎⁎⁎⁎ − 0.49⁎⁎⁎

− 0.63⁎⁎⁎⁎ − 0.43⁎⁎

− 0.56⁎⁎⁎⁎ − 0.57⁎⁎⁎⁎

1.0 1.0

0.70⁎⁎⁎⁎ 0.61⁎⁎⁎⁎

1.0 1.0

0.56⁎⁎⁎⁎ 0.60⁎⁎⁎⁎

− 0.63⁎⁎⁎⁎ − 0.43⁎⁎

K.L. Mirabeau-Beale et al. / Gynecologic Oncology 114 (2009) 353–359

357

Table 4 (continued) Variables

Insurance Insurance problems related to cancerb Early Advanced (n = 14) Degree of unmet needsb Early (n = 56) Advanced (n = 40)

MHI-17a

EORTC overall QOLa

FACT faith/Spa

Fear of recurrenceb,d

r

r

r

R

− 0.48⁎⁎n = 28 –

− 0.45⁎ (n = 28) –

− 0.53⁎⁎ n = 28 –

– (n = 25) –

− 0.62⁎⁎⁎⁎ −0.53⁎⁎

− 0.52⁎⁎⁎⁎ − 0.57⁎⁎⁎

− 0.43⁎⁎⁎ − 0.38⁎

0.42⁎⁎⁎ 0.62⁎⁎⁎

– Not significant at a 5% significance level. a Higher scores indicate better QOL. b Higher scores indicate worse QOL. c Subset of EORTC QLQ-C30/OV28. d N = 55 for early stage group unless otherwise noted. e PCL-C is Post-traumatic stress disorder checklist-Civilian. ⁎ p ≤ 0.05. ⁎⁎ p ≤ 0.01. ⁎⁎⁎ p ≤ 0.001. ⁎⁎⁎⁎ p ≤ 0.0001.

since diagnosis. PTSD diagnosis was determined using the algorithm specified by Weathers et al. (DSM IIIR) [31]. The means of MHI-17 of the study participants were compared with those of the population norms for the MHI-17 based on an outpatient clinic sample [16]. T-tests were used to compare the means for all indices between early and advanced stage disease survivors. Chi-square tests were used to determine the between group differences in categorical outcomes. Results Patient characteristics Fifty-eight early stage OCS were recruited between June 2005 and March 2006 and 42 advanced stage OCS were recruited between June 2007 and November 2007 to participate in this study. Table 2 lists the characteristics of both groups of subjects. The advanced OCS were older compared to the early stage survivors, (mean 55.1 years (SD = 11.3)), range 36–75, vs. 48.3 years (SD = 8.8), range 30–68. Survivors were mostly white (97% early and 90.5% advanced OCS), currently married (66.7% early and 61.9% advanced OCS), worked part or full-time (58.6% early and 54.8% advanced OCS) and had graduated from college or held advanced degrees (65.4% early and 45.2% advanced OCS). Despite being greater than 3 years from diagnosis with no evidence of recurrence, a number of OCS reported physical co-morbidities, including degenerative joint disease (43.9 early vs. 31% advanced), gastrointestinal distress (26.2% early vs. 17% advanced), and thyroid disease (19.1% early vs. 12% advanced). A significant proportion also reported the need for treatment or counseling for personal family problems (31% early and 19.05% advanced stage survivors), and needing prescription medication for “nerves” (33% early vs. 23.8% advanced). There were no significant changes in marital status, highest educational status, occupational status or annual income from time of diagnosis until time of interview for early and advanced staged OCS. No more than 8.6% (n =5/58) of early and 9.5% (n =4/42) of advanced staged OCS failed to respond to questions (excluding the sexuality items). The items with the greatest percent of missing data were questions about income, which were not essential to our general analysis.

emotional and sexual); or psychological state (PTSD, degree of spirituality, fear of recurrence, MHI-17, hopelessness). Better social functioning was reported by more advanced stage survivors (98.016 SD=5.4628) than early stage survivors (92. 816, SD=14.001; P =0.0247). Because early and advanced OCS did not demonstrate statistically significant differences in outcome QOL variables, Pearson product moment correlations between modifying variables and MHI-17, EORTC overall QOL, FACT faith/spirituality, and Fear of Recurrence (FOR) were conducted. The purpose of this additional analysis was to identify whether modifying factors (such as psychosocial and physical variables) correlated with QOL outcome measures in the same way for both early and advanced OCS. Table 4 shows these results, while Table 5 shows the percent of responses for selected items.

Table 5 Selected psychological factors.

FACT — spirituality

MHI-17 PCL-C (PTSD) Fear of recurrence

Beck's Hopelessness

Comparisons of QOL and adjustment of early and advanced OCS Comparison of total indices for QOL measures used is shown in Table 3. There were no statistically significant differences between early and advanced stage OCS with respect to overall quality of life; demographics (including time since diagnosis), number of unmet needs, amount of social support, complementary therapy use; physical symptoms (neurotoxicity, fatigue, co-morbidities); functioning (cognitive, physical, role,

Sexual problems

Having a reason for living (strongly agree to agree) Life being productive (strongly agree to agree) Felt peaceful (quite a bit to very much) Illness strengthened faith (quite a bit to very much) Scored at norm or above for medical outpatients Reported PTSD at diagnostic levels Are anxious when tested for CA125 (strongly agree to agree) Probably have a relapse in 5 years

I am afraid of my cancer coming back (strongly agree to agree) When I look ahead to the future, I expect that I will be happier than I am now (false) Can't imagine what life would be like in 10 years (Ttue) I have enough time to accomplish what I want to do (false) Decreased interest in sex due to cancer Decreased sexual activity due to cancer

Early stage (n = 58)

Advanced stage (n = 42)

93%

95.2%

90%

78.6%

61%

59%

47%

62%

71%

64%

6.9%

0%

59%

64%

5% (strongly agree to agree); 40% (not certain) 56%

10% (strongly agree to agree); 54% (not certain) 48%

47%

67.5%

58%

64%

32%

67.5%

54% (n = 25)

31% (n = 10)

40.5% (n = 19)

46% (n = 14)

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Physical side effects

Table 6 Complementary therapy use.

For both early and advanced stage survivors, EORTC-fatigue, nausea/vomiting, and worse sleep were similarly correlated with worse emotional status (MHI-17), lower quality of life, less spirituality and increased fear of recurrence. FACT-fatigue similarly correlated with lower emotional status and QOL in both early and advanced stage survivors. Pain and abdominal symptoms correlated with lower QOL, worse, emotional status, less spirituality and more FOR in early stage survivors, but were not significantly associated with these factors in advanced stage survivors. Neurotoxicity did not correlate significantly with any QOL measures for advanced stage survivors, but did show a significant correlation with lower QOL and increased fear of recurrence for early stage survivors.

Therapy

Functioning: physical, role, cognitive and social Physical, cognitive, and social functioning were significantly correlated with better QOL and less FOR in early and advanced OCS. These factors also correlated with greater spirituality in early staged OCS. Role functioning was only correlated with QOL, FOR and spirituality for early staged OCS. Psychological factors Psychological factors (decreased emotional functioning, poor body image, hopelessness, and PTSD) correlated with poor emotional status, lower global QOL, less spirituality and increased fear of recurrence for both groups of OCS. Nevertheless, the majority of survivors had good emotional status (MHI-17), with 71% early and 64% advanced stage survivors scoring at or above the norm for outpatients. More than 90% of early and advanced OCS reported that they had a reason for living, that their life was productive (90% early vs. 78.6% advanced stage) and that they felt “quite a bit” to “very much” peaceful (early stage 61%; advanced stage 59%). When asked if their illness had strengthened their faith and spiritual beliefs, 54% early staged OCS agreed, while 25.9% were more ambivalent (answering “a little bit” or “somewhat”). More advanced OCS felt that their illness had strengthened their faith (58.5%) than felt that it had not (29.27%). PTSD was reported by 6.9% of early staged survivors, but no advanced OCS had a diagnosable PTSD score. Most survivors were anxious when getting CA-125 testing (early stage 59%; advanced stage 64%), despite being recurrence-free for more than 3 years. About half of both groups were afraid of their cancer coming back (early stage 56%; advanced stage 48%). Complementary therapy usage In our analysis, complementary and alternative medicine (CAM) was an exploratory variable to better characterize their use by OCS. There was no significant difference between early and advanced OCS for use of CAM. Table 6 shows the frequency distribution and reason for use of the most commonly reported complementary therapies (including exercise, vitamins, prayer and massage). CAM was mostly used to improve QOL and cope with side effects of treatment, but a percentage of both early and advanced OCS reported use of prayer and imagery to shrink their cancer (prayer: 35% early and 41% advanced OCS reporting; imagery: 82% early and 78% advanced OCS reporting). Sexual functioning Sexual problems were reported by survivors independent of staging. Sexual functioning was significantly correlated with QOL, emotional status, spirituality and FOR in early stage survivors, but was not related to any of these measures in advanced survivors. Of those who answered

Exercise Early (n = 43) 74% Advanced (n = 25) 60% Prayer (personal) Early (n = 46) 79% Advanced (n = 27) 64% Prayer (from others) Early (n = 36) 62% Advanced (n = 20) 48% Vitamins Early (n = 40) 69% Advanced (n = 22) 52% Massage Early (n = 9) 16% Advanced (n = 12) 29% Imagery Early (n = 11) 19% Advanced (n = 9) 21% Yoga Early (n = 15) 26% Advanced (n = 9) 21% Acupuncture Early (n = 10) 17% Advanced (n = 9) 21% Herbal medications Early (n = 4) 7% Advanced (n = 8) 19% Meditation Early (n = 12) 21% Advanced (n = 7) 17% Journaling Early (n = 13) 22% Advanced (n = 5) 12%

Shrink cancer

Cope with side effects

Improve QOL

3 (7%) 3 (12%)

19 (44%) 10 (40%)

39 (91%) 23 (92%)

16 (35%) 11 (41%)

21 (46%) 13 (48%)

41 (89%) 22 (81%)

22 (61%) 15 (75%)

18 (50%) 13 (65%)

33 (92%) 16 (80%)

5 (13%) 3 (14%)

16 (40%) 8 (36%)

38 (95%) 18 (82%)

3 (33%) 0

5 (56%) 7 (58%)

9 (100%) 12 (100%)

9 (82%) 7 (78%)

9 (92%) 3 (33%)

11 (100%) 5 (56%)

2 (13%) 0

5 (33%) 5 (56%)

13 (87%) 9 (100%)

2 (20%) 2 ((22%)

8 (80%) 8 (89%)

9 (90%) 7 (78%)

1 (25%) 4 (50%)

1 (25%) 5 (63%)

4 (100%) 5 (63%)

3 (25%) 2 (29%)

6 (50%) 3 (43%)

12 (100%) 6 (86%)

4 (31%) 1 (20%)

7 (54%) 3 (60%)

12 (92%) 5 (100%)

the questions, 54% (n = 25) of early stage and 31% (n = 10) of advanced stage survivors reported decreased interest in sex due to cancer, while 40.5% (n = 19) of early and 46% (n = 14) of advanced stage survivors reported decreased sexual activity due to cancer. Discussion Our study demonstrates that both early and advanced OCS experience similar positive long-term adjustment, without significant differences in psychological state or overall QOL. Many survivors scored above the norm for the MHI-17, demonstrating good emotional status (71% early and 64% advanced). This may be due, in part, to patients returning to their baseline level of adjustment. Some survivor literature suggests that 1–2 years post diagnosis, patients are found to adjust well [32]. Nevertheless, certain issues remain a problem for a subset of OCS, independent of cancer stage at diagnosis. Fear of recurrence was prevalent in both groups of survivors, despite the fact that all subjects had an elapsed time of more than 3 years from diagnosis without recurrence. Moreover, it is concerning that 6.9% of early staged survivors had a diagnosable PTSD score. This may be indicative of early stage survivors being less prepared for poor outcomes (physical side effects or sexual dysfunction) than their advanced stage peers. Additionally, sexual problems were consistently a concern for all OCS. Decreased sexual interest and activity attributed to cancer affected 31–54% of survivors responding to those questions. Sexual function may be impeded by the physical rigors of surgery, decreased hormone levels, potential chemotherapy-related autonomic neuropathy as well as psychological factors (fear of recurrence and body image). Sexual problems were significantly correlated to worse body image in OCS (early: r = 0.5360, P b 0.0001, n = 46; advanced: r = 0.48923; P b 0.01; n = 31). That early staged OCS also demonstrated a correlation between sexual problems and global QOL, FOR and emotional status not seen with advanced OCS may be secondary to greater expectations of early stage OCS due to their younger age at

K.L. Mirabeau-Beale et al. / Gynecologic Oncology 114 (2009) 353–359

diagnosis and assumed better prognosis. However, given the frequency of reported dysfunction, all OCS may benefit from resources and counseling focusing on sexual functioning. Even though the majority of subjects in this comparison were not currently reporting symptoms, physical side effects (such as pain and abdominal symptoms) correlated with more QOL measures for early stage survivors than for advanced stage OCS. Early stage OCS may be more affected by their side effects because they were younger at the time of their diagnosis and had higher expectations for full recovery. This may make the presence of any physical symptoms a greater disappointment. There may also be shortcomings in the explanations we offer to these patients about what to expect in terms of functional deficits following chemotherapy even in treatment of early staged disease. There was no significant difference among OCS for use of complementary and alternative medicines (CAM), indicating that CAM use was meeting similar needs in both early and advanced OCS. Exercise, vitamins, prayer and massage remained the most common used, mostly to improve quality of life. Other studies with OCS have shown a high prevalence of fear of recurrence and sexual problems [3,4,33,34]. While the body of literature about OCS is growing, it is challenging to compare these studies since each utilizes different questionnaires and criteria for survivorship. For example, Wenzel et al. focused on women N5 years since diagnosis, while Stewart et al.'s 2001 analysis of 200 survivors who were diseasefree was for 2 years or more. Our study directly compared early and advanced OCS all of whom had no evidence of recurrence, while using identical surveys for both cohorts. Moreover, the groups of survivors compared in this study were demographically similar. Nonetheless, there are some important limitations to our study. First, the proportion of patients with early disease who refused to participate was higher than that of advanced OCS. Given that all patients were presumed to be without evidence of disease, it may be that those patients who declined participation were less distressed and so did not perceive a benefit from study participation. This could lead to an unforeseen selection bias, whereby those early staged survivors who did participate had a worse QOL, which may explain why in this sample more early staged OCS were in counseling and taking anxiety medications. Our study was not powered to assess this variable, nor was it powered to compare individually reported items (like psychological factors in Table 5) between early and advanced OCS. Early staged OCS were, on average, 6 years younger than advanced OCS, and age could also be a complicating factor limiting our ability to compare these two groups of OCS. Moreover, this mostly white, educated, married sample of survivors may not be fully generalized to a broader population, especially since they were interviewed at only one time point. The impact of treatment modality on QOL was not the focus of this study. Our study looking at the QOL of survivors of both early and late stages ovarian cancer demonstrated that better interventions are needed to alleviate psychological distress, fear of recurrence and sexual dysfunction in a subset of ovarian cancer survivors, irrespective of staging at diagnosis. Conflict of interest statement The authors declare that there are no conflicts of interest.

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