Integrative Oncology, Quality of Life, and Supportive Care

Diljeet K. Singh and Vivian E. von Gruenigen

The World Health Organization (WHO) defines health broadly as “a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.”¹ This far-reaching definition reminds us of the powerful influence we can have as practitioners not only on the number of days our patients live but also on the quality and depth of their lives. For many patients, a cancer diagnosis provides an opportunity to examine their mortality and their lives. For some, this may enable them to make considerable health-supporting changes in their lifestyle including discontinuing tobacco use, improving their diet, and adding physical activity and stress management techniques to their health regimens. Others may find themselves exploring their spiritual beliefs and examining other aspects of their life. As health care providers, we can support our patients in their efforts to achieve their optimal health throughout the life cycle.

An understanding of integrative oncology, quality of life (QOL), supportive and palliative care, symptom management, and end-of-life (EOL) care can inform our ability to address our patients’ global health needs (Figure 22-1).

FIGURE 22-1. Holistic care for the gynecologic oncology patient.

INTEGRATIVE ONCOLOGY

Definitions

The National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health defines complementary, alternative, and integrative medicine (CAM) as follows: Complementary medicine refers to use of CAM together with conventional medicine. Alternative medicine refers to use of CAM in place of conventional medicine. Integrative medicine refers to a practice that combines both conventional and CAM treatments for which there is evidence of safety and effectiveness. Practitioners describe integrative oncology as both a science and a philosophy that focuses on the complexity of the well-being of cancer patients and proposes a multitude of approaches to accompany conventional therapies to facilitate health.² In addition, integrative oncologists strive to support the innate healing abilities of the individual, using techniques for self-empowerment, individual responsibility, and lifestyle changes that could potentially reduce both cancer recurrence and second primary tumors. Integrative medicine includes biologically based practices (eg, diet, dietary supplements, herbs), mind-body medicine (eg, guided imagery, hypnosis, meditation, stress management), manipulative or body-based practices (eg, massage therapy, chiropractic, reflexology), energy medicine (eg, acupuncture, qigong, Reiki, yoga), and whole system approaches (eg, Ayurveda, traditional Chinese medicine [TCM], homeopathy) (Table 22-1).

Table 22-1 Integrative Modalities

For a number of reasons, ongoing tension exists between some aspects of integrative medicine and conventional medicine. Although the impact of diet, exercise, and stress management techniques on health is relatively well accepted, limited research and differing philosophical underpinnings have fostered distrust and knowledge gaps among conventional providers, which contribute to reluctance on the part of patients to discuss their usage with their providers. Data from well-conducted trials on the risks and benefits of complementary modalities are limited for several reasons. First, the NCCAM was only relatively recently established in 1999 as a consistent source of guidance and funding for research and training. Researchers have also identified lack of quality and substantial variability of dietary supplements as significant challenges to conducting research. The US Food and Drug Administration regulates dietary supplements as foods, not drugs, and thus does not analyze the content of dietary supplements. Whereas synthetic, single-entity drugs are relatively easy to characterize, the complexities of herbal preparations and our incomplete knowledge regarding the active components hinder research efforts. Traditional evidence-based medical research focuses on 1 variable and its impact on 1 outcome. By definition, integrative approaches imply a whole system with multiple component parts that work together toward the maximum benefit of the patient. Thus, the best-suited research programs would evaluate a whole systems approach to patients. Studies and their analysis might include psychological interventions, physical exercises, nutritional variations, and combinations of botanicals. For example, in a series of work with prostate cancer patients, Ornish et al³ used a mixed-interventions approach described as comprehensive lifestyle changes including nutritional changes, physical activity, and meditation and found decreases in prostate-specific antigen and cell and serum level changes thought to inhibit cancer progression.

Usage

The widespread use of CAM represents a challenge and an opportunity to our field; we must balance safety with our commitment to allow our patients to avail themselves of all potentially beneficial modalities. In 2008, the National Center for Health Statistics indicated that 38% of all Americans use some form of CAM.⁴ A 2005 Institute of Medicine report detailed this trend and reported that Americans were spending at least $27 billion out of pocket for CAM products and services.⁵ Use of CAM is particularly common among people with cancer. Studies indicate that up to 80% of all cancer patients use some form of CAM most commonly including acupuncture, massage, yoga, energy healing, TCM, Ayurveda, mind-body interventions, and a wide variety of vitamins, mineral supplements, antioxidants, and herbs.⁶ Studies reveal that 40% to 70% of patients do not report CAM use to their physicians for a wide variety of reasons and that most patients are willing to discuss CAM use with their physicians, but they are concerned that their physician will not understand, approve of, or have interest in these modalities. Furthermore, although increasing numbers of physicians express open attitudes toward CAM therapies, they may be hesitant to discuss this with patients because of their lack of knowledge and a desire not to appear uninformed. A survey of ovarian cancer patients revealed significant use of herbs and a perceived need among patients for guidance from their physicians.⁷

Several concerns regarding the use of herbs and antioxidants are relevant to providers of women with a gynecologic malignancy. Quality of herbal preparations has not been well governed, and contamination of preparations has been reported. However, reported cases of complications with herb use are quite rare, and with trained guidance, safe, effective products can be identified. Antiplatelet effects and prolongation of coagulation parameters can theoretically occur with ginkgo biloba, garlic, ginseng, fish oils, vitamin E, dong quai, and feverfew. Holding these herbs before surgery is reasonable; it is unclear whether their potential bleeding effects warrant prohibiting their use during chemotherapy. Neuroprotective effects of vitamin E may outweigh the theoretical risks (see Symptom Management section). Cardiovascular effects of ephedra include tachycardia, hypertension, and palpitations, and pharmacologic doses of garlic may cause hypotension. Hypoglycemia has been reported with ginseng. Pharmacodynamic herb–drug interactions include potentiating the sedative effect of anesthetics by kava and valerian, and these may be held perioperatively as well. St. John’s wort induces cytochrome P450, leading to increased metabolism of many drugs including warfarin, irinotecan, cyclosporine, oral contraceptives, digitalis, midazolam, lidocaine, and calcium channel blockers. Echinacea, goldenseal, and licroice may inhibit cytochrome P450, thus increasing circulating concenetrations of these same medications. Herbs that induce or inhibit drug metabolism should be used with caution during chemotherapy, as should other drugs known to alter metabolism.

Substantial controversy exists regarding the safety of supplemental antioxidant administration during chemotherapy and radiation.⁸ Some practitioners have raised the concern that antioxidants may decrease the efficacy of chemotherapy by interfering with its mechanism of action. Others site data that antioxidant supplements are useful in conjunction with chemotherapy because they enhance the efficacy of the chemotherapy and alleviate toxic side effects, allowing patients to tolerate chemotherapy for the full course of treatment and possibly at higher doses. From the 19 randomized controlled trials of antioxidant use during chemotherapy reviewed by Block et al, no evidence was found that supported concerns that antioxidant supplementation given with chemotherapy diminished the efficacy of the chemotherapy in study populations comprising mostly advanced or relapsed patients.⁹ In contrast, 17 of the 19 trials included in this review showed a statistically significant advantage or nonsignificantly higher survival and/or treatment response in patients given antioxidants. General and neurologic toxicities were also improved by antioxidant supplementation.

IMPACT OF LIFESTYLE ON GYNECOLOGIC CANCER

Multiple aspects of lifestyle impact on cancer risk and prognosis, including stress, social support, physical activity, and nutrition. Researchers postulate that stress-induced immunosuppression or dysregulation may contribute to the development and progression of malignancy. For example, in ovarian cancer patients, depressed and anxious mood is associated with a greater impairment of the cellular immune response and an increase in tumor progression.¹⁰ Stress can be a cofactor for the initiation and progression of cancer. The catecholamine stress hormone norepinephrine may influence tumor progression by modulating the expression of factors implicated in angiogenesis and metastasis.¹¹ Strategies to address stress in cancer patients include relaxation training, meditation, graded exercise, yoga, tai chi, and other mind-body interventions that induce the relaxation response. Social isolation is associated with an increased risk of death from cancer; thus, support groups and social connection can benefit cancer patients.

Weight, diet, and exercise are interrelated and modifiable risk factors for many diseases including cancer. Risk factors for endometrial cancer include obesity and sedentary lifestyle. Half of all endometrial cancers in postmenopausal women are attributable to being overweight (body mass index or obese . In a study of 1.2 million women enrolled in the Million Women Study in the United Kingdom, risk of endometrial cancer in obese women was almost triple that of normal-weight women.¹² Data from more than 32,000 women participating in the Women’s Health Study confirmed the relationship between BMI and risk of endometrial cancer.¹³ Women reporting any vigorous activity had lower risk than those reporting none. A large, prospective cohort study of more than 250,000 women from 9 European countries found little association between physical activity and endometrial cancer risk, although a potential risk reduction in premenopausal women was identified.¹⁴ Data from the National Institutes of Health–American Association of Retired Persons Diet and Health Study of more than 100,000 women found a dose-response relationship between vigorous activity and endometrial cancer risk but no association with light/moderate, daily, routine or occupational physical activities. The relationship between physical activity and endometrial cancer risk was also examined in the American Cancer Society Cancer Prevention Study II Nutrition Cohort of more than 40,000 postmenopausal women.¹⁵ They found that light and moderate physical activity were associated with lower endometrial cancer risk, although BMI attenuated the association. Physical activity was strongly associated with reduced risk in overweight and obese women in this study. The extent to which differences in level of physical activity contribute to endometrial cancer risk is not clear. In contrast, the relationship with BMI is unambiguous. Regardless of the direct effect of physical activity on endometrial cancer risk, women should be encouraged to maintain appropriate levels of physical activity to help maintain body weight.

BMI may influence patient outcomes and survival. In an analysis of nearly 400 early-stage endometrial cancer patients from a randomized trial of surgery with or without adjuvant radiation therapy, mortality was increased in obese patients and in morbidly obese patients, compared with lighter-weight women.¹⁶ In an analysis of patients with advanced or recurrent endometrial cancer from 5 Gynecology Oncology Group (GOG) trials who had been treated with adjuvant chemotherapy, no overall significant associations between progression-free survival (PFS) and BMI were detected. However, increased BMI was significantly associated with an increased risk of death in women with stage III/IV endometrial cancer, but not in patients with recurrent disease. Although some endometrial cancer patients gain weight after diagnosis, the effect of this weight gain on recurrence or mortality is unknown.

A recent review and meta-analysis examined the relationship between consumption of a high glycemic index or glycemic load (GL) diet and endometrial and ovarian cancer.¹⁷ The estimates for endometrial cancer showed an increased risk for high GL consumers, which was further elevated in obese women. Only 2 studies examined ovarian cancer, and results also indicate positive associations for GL.

Data evaluating obesity as a risk factor for epithelial ovarian cancer have been mixed. In a recent meta-analysis of 28 eligible studies, 24 studies reported a positive association between obesity and ovarian cancer, and in 10 studies, this reached statistical significance.¹⁸ In the European Prospective Investigation Into Cancer and Nutrition cohort of more than 200,000 women, the associations of measured anthropometric factors, including general and central adiposity and height, with ovarian cancer risk were evaluated with attention to menopausal status and specific histologic subtypes. There were approximately 600 incident cases of primary, malignant, epithelial ovarian cancer diagnosed during a mean follow-up of 9 years. Compared to normal-weight women, obesity was associated with an excess ovarian cancer risk for all women combined and for postmenopausal women, although the association was weaker for premenopausal women.¹⁹ Other studies have analyzed the relationship between obesity and ovarian cancer in regard to the duration of obesity. A study of Danish women diagnosed with ovarian cancer found that women who had been overweight during the previous 5 years had an increased risk of death compared with normal-weight women. A prospective study in China of women diagnosed with ovarian cancer also found that increased BMI 5 years prior to diagnosis was associated with reduced survival. A retrospective US study of advanced-stage ovarian cancer patients noted that obesity (BMI > 25 kg/m²) was independently associated with shorter disease-free survival and overall survival (OS).²⁰ These studies suggest that overweight/obesity is associated with reduced survival from ovarian cancer; however, the role of physical activity and benefits of modifying weight after diagnosis are not addressed in these studies.

If weight is a poor prognostic indicator, it may be postulated that these patients perhaps are receiving subtherapeutic treatment. Inconsistencies in dosing chemotherapy for obese patients have included use of body surface area, dosing at ideal body weight, dose capping, and differing measurements of renal function, all of which can underestimate dose and consequently negatively influence survival. However, in the Scottish Randomized Trial in Ovarian Cancer I study, in which more than 1000 patients received front-line chemotherapy, BMI was not associated with PFS, OS, or completeness of debulking surgery.²¹ In a separate study of nearly 800 advanced ovarian cancer patients, no association between prechemotherapy BMI and survival was observed. Weight gain was associated with improved survival; however, 50% of the patients had a BMI of < 25 kg/m², which would include women who were underweight and likely to benefit from weight gain.

Diet and Cancer Prevention

Studies of diet, nutrition, and cancer risk are restricted by retrospective collection of data, difficulty in correlating specific nutrients in food diaries, and the limitations of epidemiologic studies. In addition, advocates of integrative health approaches have objected to the reductionism of studying specific nutrients (vitamin A and β-carotene) instead of whole foods (yellow and orange fruits and vegetables), where the interactions of food components may be important. A holistic option is to study regional diets such as the Mediterranean diet.

Mediterranean Diet

The concept of the Mediterranean diet as a healthy diet was developed in the 1950s and referred to dietary patterns found in olive-growing areas of the Mediterranean region (Table 22-2). Although countries around the Mediterranean basin have different diets, religions, and cultures, common dietary characteristics have been identified and studied. The following scale was developed to determine adherence: (1) high monounsaturated-to-saturated lipid ratio, (2) high consumption of fruits, (3) high consumption of vegetables, (4) high consumption of legumes, (5) high consumption of cereals, (6) moderate to high consumption of fish, (7) low consumption of meat and meat products, (8) low to moderate consumption of milk and dairy products, and (9) moderate consumption of ethanol, mostly in the form of wine at meals. Many epidemiologic studies have demonstrated reduced risks of overall mortality, cardiovascular diseases, and several common neoplasms in adherents of the Mediterranean diet. A recent meta-analysis showed that increased adherence to the Mediterranean diet was associated with a significant reduction of overall mortality, cardiovascular incidence or mortality, cancer incidence or mortality, and neurodegenerative diseases.²² Mechanistically, researchers have proposed that the health benefits of this diet are based on bioactive compounds and their interactions, specifically monounsaturated-to-saturated fatty acid ratio, dietary fiber, antioxidant capacity of the whole diet, and phytosterol intake.

Table 22-2 Components of Mediterranean Diet

La Vecchia examined the relationship between the gynecologic cancers and specific components of the Mediterranean diet.²³ He found a significant decreased risk for endometrial and ovarian cancer when comparing lowest vegetable intake to highest. The risk for ovarian cancer was statistically decreased for women with an increase of 1 g/wk of omega-3 fatty acids (found in fish and olive oil). Highest consumption level of whole grain foods was associated with decreased risk of endometrial and ovarian cancer. Previous work by this group also showed an increase in risk of both endometrial and ovarian cancer associated with ≥ 7 servings of red meat compared with consumption of ≤ 3 servings per week.

Individual Dietary Components

Additional work has evaluated the relationship between specific dietary components and gynecologic malignancies. A review of the literature on variation in meat and fish intake found that low consumption of processed meat and higher consumption of poultry and fish may reduce the risk of ovarian cancer.²⁴ In contrast, high fish intake was associated with a reduced risk of ovarian cancer, and a frequent intake of poultry was associated with borderline significant reductions in risk of ovarian cancer. A systematic review of the role of diet on the risk of human papillomavirus (HPV) persistence and cervical neoplasia was conducted and included 23 observational studies and 10 randomized clinical trials.²⁵ The studies on HPV persistence showed a possible protective effect of fruits, vegetables, vitamins C and E, β- and α-carotene, lycopene, lutein/zeaxanthin, and cryptoxanthin.

An association between decreased vitamin D levels and increased rates of cancer has been described. Researchers have postulated that the known north-south gradient in age-adjusted mortality rates of ovarian cancer in the United States are attributable to lower solar irradiance and thus lower serum vitamin D levels. In support of this, laboratory findings have suggested that low levels of vitamin D metabolites could play a role in the etiology of ovarian cancer. The association of solar ultraviolet B irradiance, stratospheric column ozone, and fertility rates at age 15 to 19 years with incidence rates of ovarian cancer in 175 countries was examined. Age-adjusted ovarian cancer incidence rates were highest in countries located at higher latitudes. A review of the literature found that approximately half of the ecologic and case-control studies reported reductions in incidence or mortality of ovarian cancer with increasing geographic latitude, solar radiation levels, or dietary/supplement consumption of vitamin D, whereas the other half reported null associations with ovarian cancer risk.²⁶ In addition, no overall risk reduction was seen with increasing dietary/supplement consumption of vitamin D or with plasma levels of vitamin D prior to diagnosis; however, vitamin D intakes were relatively low in all studies. A serum study was performed to clarify the mixed data from ecologic studies. A case-control study of more than 7000 subjects from the National Health and Nutrition Examination Surveys demonstrated that ovarian cancer patients were 3 times more likely to have low serum vitamin D. These authors concluded that deficiency in vitamin D provides an etiologic link between the long-known ecologic findings regarding latitude.²⁷

Botanicals

Several botanicals are being investigated as agents to inhibit cancer development; they include green tea, curcumin, Astragalus, and resveratrol. A systematic review of publications on green tea research concludes that green tea may have beneficial effects on cancer prevention and that further studies, such as large and long-term cohort studies and clinical trials, are warranted. Curcumin, a component of turmeric or curry powder, has been shown to downregulate several pathways of cancer initiation and promotion. Oral curcumin is well tolerated and has biological activity in some patients with pancreatic cancer. The dried root of Astragalus membranaceus (huang qi), a traditional Chinese herbal medicine, demonstrated improvements in survival, tumor response, and performance status in a meta-analysis of randomized trials of almost 3000 lung cancer patients on platinum-based chemotherapy.²⁸ Resveratrol is a polyphenol found in numerous plant species, including grapes, that has been shown to possess chemopreventive properties against several cancers through inducing apoptosis. Additional studies of these agents in gynecologic cancer are warranted.

Researchers analyzed the association between intake of 5 common dietary flavonoids and the incidence of epithelial ovarian cancer in more than 60,000 women in the Nurses’ Health Study.²⁹ Although no clear association was found between total intake of the 5 flavonoids and ovarian cancer, there was a significant 40% decrease in ovarian cancer incidence for the highest versus lowest quintile of kaempferol intake and a significant 34% decrease in incidence for the highest versus lowest quintile of luteolin intake. An inverse association with consumption of nonherbal tea and broccoli, the primary contributors to kaempferol intake in our population, further supported this association. A study of epithelial ovarian cancer patients in China showed that habitual green tea intake was protective, and the benefit was dose- and duration-dependent. A recent prospective cohort study in more than 60,000 Swedish women followed for more than 15 years provided evidence that green tea intake reduced the risk for the development of epithelial ovarian cancer in a dose-dependent manner. A case-control study of diet and ovarian cancer in western New York involving ovarian cancer cases and controls found that compared with women in the lowest quintile of intake, reduced risks were observed for women in the highest quintile of intake of dietary fiber (57% decrease), carotenoids (67% decrease), stigmasterol (58% decrease), total lignans (57% decrease), vegetables (53% decrease), and poultry (55% decrease).

Epidemiology studies have reported associations between increased soy intake and decreased risk of endocrine-related gynecologic cancers. Myung et al³⁰ performed a meta-analysis examining the relationship between soy food intake and the risk of endometrial cancer and ovarian cancer. Compared with the lowest soy intake, the highest soy intake group had a 39% decrease in risk of all endocrine-related cancers, a 30% decrease in the risk of endometrial cancer, and a 48% decrease in risk of ovarian cancer. A case-control study of 500 women with endometrial cancer evaluated the associations between dietary intake of 7 specific compounds representing 3 classes of phytoestrogens (isoflavones, coumestans, and lignans) and risk. When comparing highest to lowest intake groups, isoflavone intake was associated with a 41% decrease in risk. In postmenopausal women, protection from isoflavones was even stronger, and a 43% reduction in endometrial cancer risk was also seen for lignan intake. Obese postmenopausal women consuming relatively low amounts of phytoestrogens had a 7-fold increase in the risk of endometrial cancer.

Diet and Cancer Prognosis

There is a paucity of research regarding nutrition and prognosis in ovarian cancer patients. In a longitudinal study of more than 300 women with ovarian cancer, longer survival was associated with total fruits and vegetables and vegetables separately. Subgroup analyses showed only yellow and cruciferous vegetables to significantly favor survival. In a population-based cohort of more than 600 women with epithelial ovarian cancer followed for up to 5 years, death was reduced in women who reported higher intake of vegetables and cruciferous vegetables. Inverse associations were seen between protein, red meat, and white meat and survival. There are no published studies of diet and endometrial cancer survival.

Regarding the relationship between individual dietary components and cancer prognosis, research has been done on vitamin D, green tea, and selenium. Studies in Norway and England found that individuals diagnosed with any cancer in summer or fall, when serum 25-hydroxyvitamin D levels are highest, had a milder clinical course and longer survival than those diagnosed in winter or spring. However, there are no vitamin D studies focused on gynecologic cancer survival after diagnosis. A small cohort study following more than 200 women with epithelial ovarian cancer demonstrated that habitual green tea consumption caused a significant dose-dependent increase in survival rate. Researchers evaluated the impact of randomized selenium supplementation in more than 30 patients with ovarian cancer undergoing chemotherapy. At 3 months, patients had significant increases in their white blood cells. After 2 to 3 months of selenium, significant decreases in hair loss, abdominal pain, weakness, and loss of appetite were noted among selenium-supplemented patients. Thus, promising data demonstrate the need for additional research to evaluate the potential for dietary modification and supplementation to improve survival and side effects in women with gynecologic malignancies.

Lifestyle and Quality of Life

Lifestyle decisions regarding nutrition, physical activity, tobacco use, and stress management not only affect cancer prevention and prognosis, but may also enhance QOL and improve patient outcomes. Physical activity may improve QOL, morbidity, and mortality in ovarian cancer patients.³¹ A study examining ovarian cancer survivors who were on and off active treatment found that those meeting public health guidelines for physical activity had lower self-reported levels of fatigue and better scores for peripheral neuropathy, depression, anxiety, and sleep quality than women not meeting guidelines. An additional study of women undergoing gynecologic surgery found that baseline characteristics such as physical and mental health, age, and body weight affect QOL scores. Therefore, regular physical activity may enhance survival by increasing QOL and improving ability to tolerate surgery and chemotherapy.

A recent study enrolled newly diagnosed ovarian cancer patients receiving adjuvant intraperitoneal (IP) or intravenous (IV) chemotherapy to a QOL lifestyle intervention trial.³² Patients were counseled in physical activity and nutrition quality. Assessments were obtained at entry to the study, during therapy (cycle 3), and after chemotherapy. Walking is the preferred mode of exercise for ovarian cancer patients. The median number of steps during the week of chemotherapy administration was less than 5000; 1 week after chemotherapy, steps increased to nearly 6000; and 2 weeks after chemotherapy, steps increased by nearly 5300. Steps were lowest after the first cycle of chemotherapy. QOL and emotional and functional well-being scores increased linearly during each cycle of chemotherapy. Therefore, it is feasible for ovarian cancer patients on adjuvant chemotherapy to increase physical activity that may improve QOL.

Lack of exercise and obesity are associated with lower QOL in endometrial cancer survivors. A survey of nearly 400 endometrial cancer survivors found that lack of exercise and excess body weight were associated with lower QOL. Approximately 70% of the women surveyed were obese and were not meeting public health exercise guidelines. Analyses showed that both exercise and BMI were independently associated with QOL. Another survey of 120 endometrial cancer survivors demonstrated that pain and fatigue decreased while physical functioning increased with physical activity. von Gruenigen et al³³ conducted a prospective observational trial in newly diagnosed endometrial patients preoperatively and 6 months postoperatively. Again, there was a correlation between weight and QOL. Weight, exercise, and fruit and vegetable intake did not change over time; however, CAM use increased significantly at 6 months. Although small, this study highlighted an important observation that may apply to endometrial cancer patients: Without intervention, survivors of endometrial cancer who are sedentary and/or obese are unlikely to spontaneously modify their exercise and nutrition behaviors after diagnosis and treatment.

It is important to implement lifestyle interventions to improve survivorship of endometrial cancer patients who are at increased risk for poor QOL and premature death secondary to obesity-driven comorbidities. A randomized controlled study of an interventional lifestyle program in 45 endometrial cancer survivors demonstrated that patients can lose weight and improve their exercise after the intervention.³¹ At 12 months, the intervention group lost 3.5 kg, compared to a 1.4-kg gain in the control group, and significantly increased physical activity. Therefore, a lifestyle intervention program in obese endometrial cancer patients is feasible and can result in sustained behavior change and weight loss over a 1-year period. This same research group is presently enrolling more than 100 endometrial cancer survivors to an intervention trial that includes both aerobic exercise and strength training.

QUALITY OF LIFE

QOL is a multidimensional concept that continues to be defined over time. QOL has been defined as an individual’s physical, functional, emotional, and social well-being and how it is impacted by a medical condition and its treatment. QOL measures are reported directly by patients and hence are termed “patient-reported outcomes.” They are not subject to interpretation by either health care providers or research professionals. QOL measurements can provide information about the impact of the disease and its treatment in cancer patients to aid physicians in selecting both antineoplastic and supportive care therapy. A recent meta-analysis of 30 randomized controlled trials from the European Organization for Research and Treatment of Cancer that included survival data for more than 10,000 patients with 11 different cancer sites found that QOL could help to predict survival in patients with cancer.³⁴

There is a paucity of data regarding QOL in early-stage ovarian cancer patients because it is not as common as advanced-stage disease. Traditionally, treatment of ovarian cancer involves removal of both ovaries and the uterus, which puts younger women into menopause and ends their chance of bearing a child. Although women with early-stage ovarian cancer often have an excellent prognosis (5-year survival > 90%), the loss of reproductive potential and lingering psychological survivorship sequelae may result in serious disruptions in QOL. A recent study by Wright et al³⁵ demonstrated that 5-year survival rates for stage I ovarian cancer patients were the same for women who had both ovaries removed and women who had just the cancerous ovary removed, suggesting that ovarian conservation may be considered in select patients.³³ This more conservative approach may result in improvements in QOL for women with early-stage disease. Matulonis et al³⁶ studied the QOL of early-stage ovarian cancer patients and observed that even though patients reported good physical QOL scores, one-third of the patients received treatment for family or personal problems, and nearly 60% reported anxiety associated with testing of CA-125.³⁴ Therefore, women with early ovarian cancer clearly benefit from support and interventions for their QOL needs.

Treatment advances for ovarian cancer patients have led to improvements in survival, allowing a broadening of care goals to include maximizing QOL. A single-institution study, in which the majority of ovarian cancer patients had advanced-stage disease, revealed that surgery significantly impacts QOL. QOL markedly decreased after surgery, with a slow improvement during adjuvant chemotherapy, specifically in the physical, functional, and fatigue domains.

Over the past 10 years, several international and GOG randomized trials have included QOL end points for evaluation. The National Cancer Institute of Canada OV10 randomized trial of nearly 700 patients identified that baseline performance status and global QOL were independent predictors of PFS and OS.³⁷ Two large-scale GOG studies (152 and 172) included QOL assessments at several time points in ovarian cancer patients with advanced disease. Wenzel et al compared QOL in patients enrolled in a randomized trial of interval secondary cytoreduction in advanced ovarian carcinoma (GOG 152). The baseline QOL score was positively associated with OS. GOG 172 randomized optimal stage III epithelial ovarian cancer patients to IV paclitaxel plus IP cisplatin and paclitaxel versus IV cisplatin and paclitaxel and found an improved OS in the IP arm.³⁸ Physical and functional well-being and ovarian cancer symptoms were significantly worse in the IP arm during and after treatment. In addition, during treatment, patients on the IP arm experienced more QOL disruption, abdominal discomfort, and neurotoxicity. However, 12 months after treatment, only neurotoxicity remained significantly greater for IP patients. In an ancillary analysis of GOG 152 and GOG 172, patients with lower QOL scores had declines in physical, functional, and emotional well-being. In the physical domain, significant differences were observed in physical symptoms (nausea, pain, feeling ill, and being bothered by the side effects of treatment), as well as more general effects (lack of energy, meeting needs of family, and forced to spend time in bed). These patients were least likely to sleep well. Regarding emotional well-being, there were significant differences in feeling nervous and worrying about dying.

Limited studies have been performed specifically assessing QOL in women with endometrial cancer. Limitations of prior research have included heterogeneous gynecologic populations and different adjuvant therapies, and the studies have not been well controlled. A recent, large study compared QOL among 5- to 10-year survivors of stage I to II endometrial cancer treated with surgery alone or surgery with external beam adjuvant therapy.³⁹ Comorbidity appeared to be the only variable that was negatively associated with all QOL subscales. On multivariate analyses, adjuvant radiation was negatively associated with vitality and physical and social well-being scale scores. Unfortunately, BMI was not a controlled variable. In addition, the current adjuvant treatment for endometrial cancer patients at intermediate risk for recurrence is vaginal radiation not pelvic radiation. In addition, no studies have assessed obesity as the key variable of QOL in endometrial cancer.

QOL is compromised in endometrial cancer survivors, but not for the same reasons as in ovarian cancer patients. A recent ancillary analysis of 2 prospective endometrial cancer QOL trials revealed that scores were similar to normative data in age-matched women without cancer. BMI was inversely correlated with functional, physical, and social well-being and with several decreases in line items within the functional domain, including ability at work and being content. BMI also had an inverse relationship with the “lack of energy” item in the physical domain. Fatigue was present in nearly 30% of survivors, which increased as weight increased.

SUPPORTIVE CARE

Stay updated, free articles. Join our Telegram channel

Join