Psychological Responses and Coping Strategies Among Patients With Malignant Melanoma: Title and subTitle BreakA Systematic Review of the LiteratureCoping Strategies and Patients With Melanoma FREE

Despite continued progress in the medical management of many malignant diseases, the diagnosis of cancer, including melanoma, remains a difficult event in the lives of many patients and their families. Clinical impressions and research findings suggest that a diagnosis of melanoma has the potential to change all aspects of an individual's daily living from self-identity, body image, and perceived well-being, to family roles and relationships, career opportunities, friendships, and finances.^{1 - 2} The distress evoked by such changes may have wide-ranging implications. Psychological distress has been associated with patient delay in seeking medical advice for melanoma, decreased adherence to treatment regimes, increased rates of melanoma recurrence and mortality, lower quality of life (QOL), increased medical costs, and reduced engagement in posttreatment skin cancer screening and preventive behaviors.^{3 - 5} Thus, understanding the prevalence and correlates of psychological distress and developing interventions to reduce distress remain critical research and clinical endeavors.

According to the Surveillance, Epidemiology, and End Results (SEER)⁶ data from 1995 to 2001, 83% of melanoma cases in the United States are diagnosed while the cancer is still confined to the primary site, yielding good prognoses.⁷ This, coupled with the often healthy outward appearance of patients with early-stage melanoma, may contribute to the prevailing belief that such patients have little or nothing to worry about.^{8 - 10} Despite a good prognosis, however, patients with early-stage melanoma deal with both the immediate stress of being diagnosed with a possibly life-threatening disease as well as the threat of recurrence or systemic spread, which is greatest during the first 2 years after diagnosis but may occur within 10 years of diagnosis. Several studies have also found evidence to suggest that some patients with melanoma experience an underlying fear of disfigurement caused by cancer surgery, and that the visibility of treatment-related scarring may form a constant reminder of the individual's cancer experience,⁸ irrespective of the body site affected.^{3 ,8 ,11} Disfiguration of bodily appearance may threaten patients' self-esteem and self-confidence,^{4 ,12} particularly in younger adult age groups, among whom melanoma is the most common malignant disease.⁵ Thus, seemingly high-functioning patients with early-stage melanoma may be overlooked by family, friends, and health care professionals in terms of social and psychological support, potentially exacerbating feelings of anxiety and/or depression.¹⁰

Synthesizing previous research findings, the aims of the present review were 4-fold: (1) to systematically review the body of literature on the prevalence of psychological distress among individuals affected by melanoma; (2) to compare these findings with the limited number of studies assessing psychological distress among individuals at increased risk of developing melanoma due to strong family history; (3) to identify the demographic, clinical, psychological, and/or social predictors of distress in these populations; and (4) to examine the various coping strategies commonly adopted by patients with melanoma. The findings of the review were then used to develop a series of evidence-based clinical recommendations for the supportive care of patients with malignant melanoma. Ways in which the empirical literature may be used to inform the development of a brief, tailored screening tool for the identification of patients with melanoma who are most susceptible to adverse psychological outcomes, as well as the cost-effective design and implementation of appropriate psychological interventions in this setting, are also discussed.

Three strategies were used to conduct the literature search. First, the electronic databases MEDLINE, MEDLINE In-Process, PsycINFO, and CINAHL were searched from January 1988 to March 2008 using the keyword “melanoma” in combination with each of the following terms: depression, anxiety, adjustment, psychological adjustment, distress, psychological distress, worry, cope, and coping. We agreed on the inclusion and exclusion criteria before commencement of the review (Table 1). Studies were considered eligible for inclusion in the review if they were published in a peer-reviewed journal or were otherwise in the public domain in a peer-acceptable format. Multiple articles that seemed to describe overlapping patient populations were grouped together and, where necessary, only the data from the largest study population or the most recent article in these groups were reviewed. Second, the resulting list of publications was then screened for nonresearch articles, duplicates, and irrelevant references such as single case reports, letters, commentaries, or conference abstracts. Third, the reference lists of all publications identified were examined for relevant articles not captured by the initial literature search.

This review is concerned with the psychological responses of patients with melanoma, and the term “melanoma-specific distress” will be used hereinafter to denote emotional distress specific to some aspect of an individual's melanoma diagnosis and/or treatment. This form of distress is typically assessed via administration of the Impact of Events Scale (IES), a validated 15-item measure of intrusion and avoidance responses in relation to a specific stressor, in this case melanoma. Where reference is not made to melanoma-specific distress, the emotional responses described should be considered generalized. A wide range of scales have been used to measure psychological distress, and in some instances clinical cutoff scores are provided for these scales (eg, the Hospital Anxiety and Depression Scale [HADS], Brief Symptom Inventory, Beck Depression Inventory). These cutoff scores allow clinicians and researchers to identify patients recently experiencing psychological symptoms of a severity that may warrant clinical intervention; for example, a potential diagnosis of clinical depression. Despite differences between scales in terms of item wording and response format, clinical cutoff scores are typically considered comparable across scales.

The initial search yielded 569 articles. After deletion of duplicates (n = 213), the exclusion of 313 articles according to our predefined criteria (Table 1), and the inclusion of 1 article identified by citation within the reference list of a selected publication, 44 articles were identified for review. These articles were examined and their results tabulated. In accordance with the National Health and Medical Research Council (NHMRC) of Australia evidence rating system,¹³ most relevant articles provided level IVa evidence; that is, evidence obtained from descriptive studies of patient behaviors, knowledge, and/or attitudes. The remaining articles provided level III evidence; that is, evidence obtained from well-designed controlled trials without randomization, well-designed cohort or case-control studies, or multiple time series with or without an intervention.

Although a small number of studies document general emotional well-being and resilience among persons diagnosed as having melanoma,^{10 ,14 - 17} a much larger number of studies have identified a considerable proportion of patients who experience elevated levels of psychological distress around the time of melanoma diagnosis and treatment. These studies indicate that, on average, approximately 30% of all patients with melanoma report levels of psychological distress indicative of the need for clinical intervention, as measured by a range of validated scales.^{1 ,18 - 19} In comparison with other cancers, the proportion of patients with melanoma who report clinically relevant levels of distress is equivalent to that identified in patients with breast and colon cancer and demonstrably higher than the prevalence of distress found among patients with gynecological and prostate cancer.¹

The prevalence of anxiety and depression in patients with melanoma is often reported in the literature concurrently because these internalizing states share similar features of negative affect, emotional distress, and significant interference in daily life. However, anxiety and depression may be differentiated by the presence of particular symptoms that are unique to each disorder. Anxiety is characterized by symptoms of excessive, pervasive, and uncontrollable worry, whereas depression is typified by symptoms of low mood and diminished interest or pleasure in most activities.²⁰ Gibertini et al¹⁹ reported that approximately 1 in 5 patients newly diagnosed as having nonmetastatic melanoma have some form of treatable depression, whereas Sigurdardóttir et al¹⁶ reported that approximately 1 in 4 patients with melanoma beginning chemotherapy report clinically relevant levels of anxiety. Anxiety seems to be more prevalent than depression, with studies reporting the percentage of participants within the clinical range on the HADS to be around 23% and 11% for anxiety and depression, respectively.^{17 ,21 - 24}

There is, however, substantial variability between studies in regard to the prevalence of reported anxiety and depression. Among patients with nonmetastatic melanoma, the proportion of participants scoring within the clinical range for anxiety on the HADS has been reported to range from 18% to 44%.^{18 ,24 - 25} Similarly, the pervasiveness of clinically relevant depressive symptoms among patients with early-stage melanoma is reported to be 6% to 28%.^{24 - 26} Only 3 studies^{16 - 17 ,24} have reported the prevalence of clinically relevant levels of anxiety and depression in patients with metastatic disease or more aggressive tumors (thickness >0.8 mm). These studies also report wide variation, with the prevalence of anxiety ranging from 13% to 28%, and the prevalence of depression ranging from 4% to 19%.^{16 - 17 ,24} Wide variation in the prevalence of clinically relevant distress among patients with melanoma may reflect important differences between study samples in terms of time since diagnosis and/or treatment, involvement in clinical trials, and/or cultural attitudes or beliefs. Limitations such as retrospective study design, lack of control or comparison groups, failure to adjust for disease severity, reliance on single assessments of psychosocial status, and small sample sizes also impede the generalization of findings.

Other researchers have assessed the psychological impact of melanoma from a posttraumatic stress (PTS) response framework. From this perspective, 2 key symptom clusters are considered critical to understanding psychological responses to melanoma diagnosis and/or treatment. These are (1) intrusion, defined as disturbing, persistent, and unwanted images, thoughts, and feelings, often accompanied by autonomic arousal, hypervigilance, and marked anxiety; and (2) avoidance, marked by ignoring the implications of threat, forgetting important problems, and experiencing emotional numbing.²⁷ Advocates of this perspective argue that the assessment of PTS provides valuable clinical information concerning psychological adjustment in patients with cancer, survivors, and their immediate family.²⁸

Kelly et al²¹ were one of the first groups to examine PTS responses in a cross-sectional study of 95 patients with stage I to stage IV melanoma. Using the IES to quantify levels of intrusive and avoidant symptoms related to melanoma diagnosis, this study identified patients with stage III disease (ie, nodal metastasis) as having significantly greater stress symptoms compared with patients with stage I disease, with a trend in the same direction compared with patients with stage II or stage IV disease (ie, distant metastasis).²¹ A similar result was also found when participants with nonmetastatic melanoma were classified according to tumor thickness, suggesting an association between PTS and prognostic indication.²¹ These findings were not replicated using the HADS, leading the authors of that study to suggest, similarly to Brandberg et al,²⁴ that IES symptoms may be more sensitive indicators of the differing psychological concerns emerging across the spectrum of melanoma progression.

As noted, anxiety symptoms also seem to be more frequently reported by individuals affected by melanoma compared to those with depressive symptoms.^{17 ,24} Furthermore, Baughan et al²⁹ found that 54% of patients with melanoma attending a routine follow-up appointment at a pigmented lesion clinic reported some degree of anxiety prior to their consultation, with 17% of these patients also reporting physical symptoms of anxiety such as diarrhea, nausea, and sleeplessness. These data lend additional support for the specific assessment of PTS, as linked to the spectrum of anxiety disorders, in analyses of the psychological impact of melanoma, and highlight the need for melanoma-related concerns to be examined as significant dimensions of psychological morbidity.

To our knowledge, since 1988, only 2 studies^{30 - 31} have specifically investigated psychological distress among families with an inherited pattern of melanoma (ie, multiple melanoma cases in the family and a family-specific mutation in the CDKN2A gene). Recently, Kasparian et al³⁰ examined psychological outcomes in this context and found that among individuals unaffected by melanoma but at high risk of developing the disease due to family history, only 1% of participants exhibited clinically relevant levels of melanoma-specific distress. Surprisingly, this study found no evidence of clinically relevant melanoma-specific distress among high-risk individuals with a previous diagnosis of melanoma. Similarly low levels of depressive symptoms were reported by those with, and those without, a personal history of melanoma, whereas levels of anxiety were comparable with population norms, with 5% of previously affected participants and 15% of unaffected participants reporting anxiety potentially warranting clinical intervention. Thus, overall the level of reported distress in this familial melanoma cohort was relatively low, even after notification of the presence of a family-specific mutation in the CDKN2A gene which, in Australia, confers an estimated lifetime melanoma risk of 91%.³¹

To date, and to our knowledge, the only other published study to shed light on the psychological experiences of individuals with a strong family history of melanoma was that conducted by Riedijk et al.³² This study examined psychological distress among high-risk individuals from p16-Leiden families who had chosen to decline genetic testing for melanoma risk, and, in agreement with the findings reported by Kasparian et al,³⁰ these researchers found that only a small proportion (7.6%) of participants reported elevated levels of anxiety. It is possible, however, that the factors associated with the decline of genetic testing may also be related to the low levels of reported anxiety.

Over the past 20 years, very few studies have used multivariate analysis to elucidate the factors contributing to higher levels of psychological distress in the population of patients with melanoma. In total, only 5 of the 44 articles included for review provided explanatory analysis of the variance in distress. As shown in Table 2 A and Table 2 B, this limited literature has identified a variety of measurable, and in some cases relatively stable, variables that may be predictive of psychological distress in individuals affected by melanoma.

Several studies have found that women,^{8 ,10 - 11 ,15 ,17 ,22 ,40 ,43 - 44} those younger in age,^{11 ,22} and those who are unmarried,^{38 - 39} with fewer children,^{38 - 39} or with lower levels of education¹⁴ are more likely to report symptoms of psychological distress. Furthermore, 2 studies have identified an association between unemployment and increased psychological distress.^{8 ,38}

Patients diagnosed as having advanced disease,^{8 ,21} a deterioration of physical condition,³⁹ or with tumors located on visible parts of the body, such as the face or hands,⁸ have been found to report higher levels of psychological distress. In several studies, stage of cancer at diagnosis and time since diagnosis were not found to be significant predictors of general distress,^{21 ,33 ,38} but there are some data to dispute this, particularly in terms of depression²⁴ and melanoma-specific distress.²¹ This finding is surprising given the substantial differences in treatment and prognosis between early- and late-stage melanoma; however, it does support the importance of subjective appraisal in psychological adjustment to disease. For example, compared with those who experience low levels of distress, individuals who report high distress levels have also been found to report significantly worse evaluations of current and future personal health, higher ratings of pain intensity, decreased energy ratings, and greater interference from physical and emotional problems on social activities.¹⁸

In terms of psychosocial predictors of distress, Hamama-Raz and Solomon³⁸ and Hamama-Raz et al³⁹ reported that a lower appraisal of melanoma as threatening and a confident appraisal of one's subjective ability to cope with the situation were predictive of reduced psychological distress. Religious beliefs were also predictive of lowered levels of anxiety and depression, as was the use of more active coping styles.³³ A recent study of high-risk individuals by Kasparian et al³⁰ found that believing that melanoma has important implications for one's family and a tendency to monitor or search for risk-relevant information were predictive of melanoma-specific distress. Of particular concern is the potential for a downward spiraling link between psychological symptoms and QOL. Lehto et al,⁴⁰ for example, reported the presence of psychological and depressive symptoms as key predictors of poor QOL. Furthermore, a substantial decrease in an individual's physical QOL has been shown to be another important correlate of psychological distress.^{10 ,18}

The ways in which patients cope with melanoma may have a profound influence on their immediate and long-term psychological, social, and physical health.⁴⁵ In a key article describing 10 strategies to promote psychological adjustment to melanoma, Kneier⁴ defined coping as the attitudes, beliefs, and behaviors that have an adaptive purpose when one is faced with a threatening situation. Viewed from this perspective, coping may be conceptualized as a primary mediator of the impact of stressful events on outcomes.⁴⁶ The aims of coping, according to Kneier,⁴ are to safeguard and protect the emotional state of the individual and to allow for psychological adjustment to aversive conditions. Kneier⁴ posited that facing the reality of one's illness, maintaining hope and optimism, expressing one's emotions, seeking support from others, adopting a participatory (as opposed to avoidant or passive) stance, and maintaining self-esteem are among the most useful strategies an individual affected by melanoma can implement to cope with the varied aspects of their diagnosis and/or treatment.

Three general theoretical coping styles, among those that have been identified in the psycho-oncology literature, are (1) active-behavioral coping, which refers to overt behavioral attempts to deal directly with cancer and its effects, such as relying on others for support; (2) active-cognitive coping, which includes one's attitudes, beliefs, and thoughts about cancer; and (3) avoidance coping, which refers to attempts to actively avoid the problem or indirectly reduce emotional tension through the use of distraction. Overall, studies suggest that patients who use active (problem-focused) coping strategies demonstrate better adjustment to melanoma than those who use passive or avoidant coping styles.^{9 - 10 ,15 ,18 ,40} By and large, patients who have used active-behavioral methods of coping have reported higher levels of self-esteem and vigor, fewer physical symptoms, and less anger and fatigue.^{9 ,45} In contrast, positive correlations have been demonstrated between avoidance coping methods and anxiety, depression, confusion, and total mood disturbance in patients with early-stage melanoma.⁹

In numerous studies of patients with cancer, social support (eg, sharing thoughts, emotions, and concerns with others) has been associated with enhanced QOL and better disease outcome^{47 - 48} and is generally thought to play a critical role in the psychological adjustment of patients, including those with melanoma.^{2 ,49} Söllner et al⁴² argue that social support and coping are strongly interdependent. Examining the combined effects of coping behaviors and perceived social support in a homogenous sample of patients with melanoma, Söllner et al⁴² found that different coping-support patterns correlated with adjustment to melanoma. A high level of social support combined with active coping or stoicism was associated with good adjustment, whereas low social support combined with depressive coping was associated with poor adjustment. Given the cross-sectional nature of this study, however, causality cannot be inferred from these results.

In a prospective study of 53 patients with metastatic melanoma and renal cell cancer, Devine et al⁵⁰ found that greater social support and fewer intrusive and avoidant thoughts before treatment predicted better psychological adjustment 1 month after treatment.⁵⁰ Moreover, the effect of social support on adjustment was mediated, at least in part, by fewer intrusive and avoidant thoughts before treatment. Devine et al⁵⁰ accounted for these findings by suggesting that social support may facilitate the cognitive processing of a traumatic event, allowing patients to ascribe meaning to the threat and assimilate the cancer experience into their views of the self and the world. In contrast, Baider et al¹⁵ did not find an association between melanoma-related distress and degree of perceived social support. In contrast again, Holland et al¹⁰ reported a significant negative association between social support and psychological distress.

Seeking to explore the extent to which personal spiritual and/or religious belief systems might be associated with levels of distress and ways of coping with malignant melanoma, Holland et al¹⁰ found that while scores on the Systems of Belief Inventory (SBI)⁵¹ did not correlate with distress, greater reliance on spiritual or religious beliefs was associated with active-cognitive coping. This association between religious beliefs and active-cognitive coping style was also reported by Baider et al,¹⁵ as well as significant negative correlations between spirituality and anxiety, depression, anger, and confusion. Fawzy et al⁹ defined this coping style as an individual's acceptance of his or her illness and the patient's attempt to view its effects in a positive, meaningful manner.⁹

In a longitudinal study on coping with metastatic melanoma during the last year of life, Brown et al³⁴ found that as terminally ill patients moved closer to death, the use of active coping strategies increased, even though the patients also experienced increasing levels of tiredness and deterioration in mood and daily functioning ability.³⁴ These patients were found to increasingly use strategies such as information seeking, meditation, and social support. Issues of enhanced self-care and family support are prominent concerns for patients with advanced melanoma. Holland et al¹⁰ also found that those with advanced disease used more active coping styles as well as more social support than patients with early-stage disease.

This suggests that patients' coping styles vary over the course of their illness, possibly in response to changing psychosocial and physical demands.³⁴ A summary of the reviewed literature and a series of evidence-based clinical recommendations for the supportive care of patients with malignant melanoma are presented in Table 3.

Conducting a systematic search of the literature on psychological morbidity among individuals affected by malignant melanoma, we identified 44 original studies published in English from January 1988 through March 2008. This review demonstrated that not all patients with melanoma exhibit clinically relevant levels of psychological distress or need intensive psychological support. Indeed, many patients with melanoma adjust and cope well. Yet, approximately one-third of individuals experience substantial difficulty adjusting to, or coping with, the diagnosis and/or treatment of malignant melanoma, and the symptoms of psychological distress may have wide-reaching implications for these patients and their families. A number of empirically demonstrated risk factors for psychological distress were identified from the available literature, including demographic factors such as female sex, younger age, absence of a spouse or partner, and lower levels of education; clinical factors such as greater physical deterioration or visibility of affected body site; and psychosocial factors, such as negative cognitive appraisals of melanoma and lack of social support. In addition, this review found evidence for a positive association between active-cognitive coping styles and healthy emotional adjustment to melanoma. Furthermore, patients who report depressive symptoms also show greater interest in receiving mental health support in addition to standard medical care.⁸ The review did, however, reveal a lack of prospective studies in this area of research. It is also clear from this review that most studies assessing psychological responses to malignant melanoma are purely descriptive in nature. Clearly, there is a need for more rigorously designed studies that are adequately equipped to reliably elucidate the factors contributing to psychological morbidity among patients with melanoma.

A recent, landmark Institute of Medicine report commissioned by the National Institutes of Health⁵⁸ has suggested that some of the most basic psychological and social issues affecting patients with cancer are not being adequately addressed in the clinical setting. In response to this, it is argued that psychosocial care is essential as the standard of care for all patients with cancer.⁵⁸ Routine psychological screening of patients with melanoma is widely recommended as standard practice in many countries, including Australia, the United States, and the United Kingdom⁵⁹ ; however, standard psychological screening measures may have limited sensitivity and specificity as demonstrated by the wide range of results reported herein. The development of a brief screening tool that incorporates empirically supported risk factors as identified by the literature is recommended to improve the timely identification and support of those patients with melanoma who are most susceptible to adverse psychological outcomes. There is also some evidence to support the clinical evaluation of PTS responses among patients with melanoma, and this may be achieved in a timely, reliable, and cost-effective manner via the administration of validated and situation-specific assessment tools, such as the revised IES.⁶⁰ Patients identified as vulnerable should be referred to psychosocial health professionals who can gauge the patients' cognitive appraisals of melanoma, as well as their capacity to cope emotionally with this disease and its treatment. Future studies focusing on the routine assessment of psychological distress responses among patients with melanoma in the clinical setting, and the implications such assessments have on appropriately targeting the provision of psychological services, are needed.

In terms of appropriate and effective psychological interventions, clinical practice guidelines for the management of melanoma consistently recommend that structured psychosocial interventions and psycho-education be made available to all patients.⁵⁹ Fawzy⁴⁵ and Fawzy et al^{9 ,54 ,61 - 62} and Boesen et al⁶³ have demonstrated that structured interventions offering psycho-educational support can reduce distress and mood disturbances and lead to greater use of active coping strategies among individuals affected by melanoma. In a series of seminal articles evaluating the short- and long-term outcomes of a 6-week structured psycho-educational group intervention, Fawzy et al^{9 ,62} reported that, despite moderate to high levels of distress at baseline, participants reported significantly lower levels of distress compared with controls at intervention completion. The intervention implemented by Fawzy et al⁹ consisted of 4 key components: (1) health education specific to melanoma, its treatment, recurrence reduction, and nutrition; (2) stress management; (3) coping and problem-solving techniques; and (4) psychological support. Six months after intervention, group differences were even more pronounced, with the intervention group, on average, demonstrating lower levels of depression, confusion, fatigue, and total mood disturbance, as well as higher levels of vigor.⁹ Beneficial effects of the intervention on immune function were also demonstrated, including an increase in certain types of natural killer (NK) cells and an increase in the tumor-fighting potential of NK cells.⁶¹ At the 5-year follow-up, these researchers were able to show that these psychological and biological changes were, in turn, associated with superior recurrence and survival rates.⁶²

As evidence for the clinical effectiveness of such psychological programs continues to grow, studies evaluating the fiscal cost associated with provision of supportive care interventions are also necessary to allow for adequate allocation of limited resources. For example, Bares et al⁶⁴ have recently provided evidence for the cost-effectiveness of cognitive behavioral therapy for patients with heterogeneous melanomas compared with standard care. Also, although this review did not yield any studies on the effectiveness of pharmacotherapy with patients with melanoma, numerous studies with other patients with cancer have demonstrated the efficacy of a combination of supportive psychotherapy, cognitive behavioral techniques, and pharmacotherapy in the treatment of anxiety and depression.^{65 - 66} Published data of this sort are needed for melanoma. Furthermore, as our knowledge of the genetics of melanoma continues to evolve, research efforts aimed at understanding the experiences and needs of individuals with an inherited pattern of melanoma are required.

From his extensive work on the psychological experiences of patients with cancer, Spiegel⁶⁷ has argued that all patients who show emotional distress, receive low levels of social support, and/or experience tumor-related difficulties in various aspects of daily life should be offered psychological support, irrespective of whether they meet the criteria for psychiatric disorder. Accurate detection of distress, or identification of those most vulnerable to developing negative psychological symptoms, can enable health professionals to initiate early intervention, tailor assistance to meet individual needs, and effectively target limited health care resources to reduce patient suffering.^{10 - 11 ,45} The clinical care of patients with severe or life-threatening conditions such as melanoma also poses special burdens for clinicians. Recognition and understanding of the emotional issues for health professionals will allow strategies to be developed to address these concerns; a process likely to lead to improved therapeutic relationships and enhanced professional satisfaction.¹³

Correspondence: Nadine A. Kasparian, BA (Psych, Hons I), PhD, Psychosocial Research Group, Dickinson Building Level 3, Prince of Wales Hospital, High Street, Randwick, NSW 2031 Australia (N.Kasparian@unsw.edu.au).

Accepted for Publication: June 15, 2009.

Author Contributions: Dr Kasparian had full access to all of the reviewed articles and takes responsibility for the integrity and accuracy of the reported findings. Drs Kasparian and McLoone share first authorship on this article. All authors were involved in the formulation of the research question and the identification of specific inclusion and exclusion criteria for this review. Drs Kasparian and McLoone conducted the literature search, reviewed all articles, tabulated all relevant articles, and assessed each article to determine evidence rating level. Dr Kasparian produced the first draft of the manuscript and incorporated the contributions of Dr McLoone and Dr Butow in subsequent drafts. Study concept and design: Kasparian and Butow. Acquisition of data: Kasparian and McLoone. Analysis and interpretation of data: Kasparian, McLoone, and Butow. Drafting of the manuscript: Kasparian, McLoone, and Butow. Critical revision of the manuscript for important intellectual content: Kasparian, McLoone, and Butow. Obtained funding: Kasparian. Administrative, technical, and material support: McLoone. Study supervision: Kasparian and Butow.

Financial Disclosure: None reported.

Funding/Support: Dr Kasparian is supported by a Postdoctoral Clinical Research Fellowship from the National Health and Medical Research Council of Australia (NHMRC ID 510399). Dr Butow is supported by a Research Fellowship from the NHMRC (ID 211199). This project was also supported by The Cancer Council NSW Strategic Research Partnership Grant (ID SRP06-X5) and a Cancer Institute NSW Program Grant for Excellence in Translational Research.