INTRODUCTION
Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. There has been increasing clinical interest in HCC over the past decades because of its increasing incidence in low-risk areas as well as a persistent high fatality rate worldwide (Ferlay et al., Reference Ferlay, Shin and Bray2010). Despite advancement in screening techniques, HCC is frequently diagnosed at an advanced stage with limited treatment options and a dismal prognosis (Teo & Fock, Reference Teo and &2001; Sun et al., Reference Sun, Ferrell and Juarez2008; Fielding, Reference Fielding, Holland, Breitbart and Jacobsen2010; Forner et al., Reference Forner, Reig and de Lope2010). The purpose of this review was to address problems of people diagnosed with advanced HCC in mainland China and to identify promising clinical interventions to improve their quality of life (QOL).
EPIDEMIOLOGY
HCC, the major type of primary liver cancer (PLC) (Wu et al., Reference Wu, Tang and Sun2011), represents the fifth most common tumor worldwide and the third most frequent cause of cancer-related death (Sun et al., Reference Sun, Ferrell and Juarez2008). The incidence of HCC differs in different geographical regions as well as in geo-economic zones within countries (Yuen et al., Reference Yuen, Hou and Chutaputti2009). Almost 85% of cases of liver cancer occur in Asia, and China alone accounts for 55%, the highest HCC burden worldwide (Parkin et al., Reference Parkin, Bray and Ferly2005; Ferlay et al., Reference Ferlay, Shin and Bray2010). The prognosis of patients with unresectable HCC remains poor, with a median survival of <1 year (Llovet et al., Reference Llovet, Di-Bisceglie and Bruix2008a). According to the recent consensus report of China, HCC is the second most common cause of cancer-related death in this country, exceeded only by lung cancer (Wu et al., Reference Wu, Tang and Sun2011).
The major risk factor of HCC in China is hepatitis B virus (HBV) infection followed by hepatitis C virus (HCV) infection, with odds ratios reported to be 12.45 and 4.28, respectively (Yuen et al., Reference Yuen, Hou and Chutaputti2009). The incidence rate of HCC in China starts to increase from the age of 35–40 years, peaking in the sixth and seventh decades of life for men, possibly later for women. Although it may occur in every adult age stratum, Chinese males have a higher HCC incidence risk than do females (Yuen et al., Reference Yuen, Hou and Chutaputti2009).
Over the past several decades, the global patterns of HCC have undergone substantial changes, with declining trends reported in Asia and a consistent incidence increase detected in Europe and North America (McGlynn et al., Reference McGlynn, Tsao and Hsing2001; Allen & Venook, Reference Allen and Venook2004; Yuen et al., Reference Yuen, Hou and Chutaputti2009). Reasons for both the decreased incidence in high-rate areas and increased incidence in low-rate areas are not fully understood (McGlynn et al., Reference McGlynn, Tsao and Hsing2001). Some suggest that the increase in low-rate areas may be related to the increased prevalence of HCV infection (McGlynn & London, Reference McGlynn and London2005; Rampone et al., Reference Rampone, Schiavone and Martino2009), whereas introduction of universal vaccination for HVB appears to have contributed to the decline in the incidence of Asian countries (Teo & Fock, Reference Teo and &2001).
There is no consensus on a given HCC staging system to guide clinical treatment decisions. Because of the complexity of the prognosis of HCC, it is recommended that tumor stage, liver function, and other factors be taken into consideration in clinical treatment decisions, as seen in Barcelona Clinic Liver Cancer (BCLC) staging system (Bruix & Sherman, Reference Bruix and Sherman2005; Rampone et al., Reference Rampone, Schiavone and Martino2009; Forner et al., Reference Forner, Reig and de Lope2010). This system links five stages with treatment modalities based on published response rates (Forner et al., Reference Forner, Reig and de Lope2010). For example, patients with very early HCC (stage 0) are optimal candidates for resection, and patients with intermediate HCC (stage B) have been found to benefit from transarterial chemoembolization (TACE). Sorafenib, a multitarget tyrosine kinase inhibitor, was recently confirmed to be a standard of care for people with advanced stage (stage C) disease (Llovet et al., Reference Llovet, Ricci and Mazzaferro2008b; Forner et al., Reference Forner, Reig and de Lope2010, Reference Forner, Llovet and Bruix2012), whereas end-stage (stage D) disease will receive symptomatic treatment. It is important that a specific profile of the patient be examined for personalizing each individual treatment decision, which becomes paramount in complex situations such as unresectable HCC (Llovet et al., Reference Llovet, Real and Montaña2002; Bruix et al., Reference Bruix, Sala and Llovet2004; Forner et al., Reference Forner, Reig and de Lope2010).
CONTROVERSIAL TREATMENT OF ADVANCED HCC
TACE was introduced in the 1980s, aiming for tumor necrosis while preserving as much functional liver tissue as possible; it remains one of the most widely used methods of treating unresectable HCC. TACE may improve median survival for 3–4 months (Llovet & Bruix, Reference Llovet and Bruix2003); this benefit seldom happens in advanced stages because of limited opportunity of complete response and almost unanimous recurrence during this time (Bruix & Llovet, Reference Bruix and Llovet2002; Bruix & Sherman, Reference Bruix and Sherman2005; Forner et al., Reference Forner, Reig and de Lope2010). Repeated embolization in short periods of time may bring serious side effects, known as postembolization syndrome (PES). This syndrome consists of abdominal pain, fever, nausea, vomiting, fatigue, and ileus, accompanied by changes in liver biological indexes. Symptoms are highly heterogeneous in patients, depending upon the disease stage and dose of chemotherapy, as well as the patient's overall health condition. The etiology of PES is not entirely known, but it is thought to be caused by a combination of tissue ischemia and an inflammatory response to chemoembolization (Vogl et al., Reference Vogl, Naguib and Nour-Eldin2009). It is experienced by 60–90% of patients, lasting from hours to days (Ramsey & Geschwind, Reference Ramsey and Geschwind2002; Bruix et al., Reference Bruix, Sala and Llovet2004; Yan & Sellick, Reference Yan and Sellick2004; Bruix & Sherman, Reference Bruix and Sherman2005; Guo, Reference Guo2005; Llovet et al., Reference Llovet, Di-Bisceglie and Bruix2008a; Sun et al., Reference Sun, Ferrell and Juarez2008; Wu et al., Reference Wu, Dugoua and Eyawo2009; Forner et al., Reference Forner, Reig and de Lope2010; Oliveri et al., Reference Oliveri, Wetterslev and Gluud2011), often resulting in a prolonged postprocedural hospitalization (Vogl et al., Reference Vogl, Naguib and Nour-Eldin2009).
Increasing clinical as well as research attention has been put on the impact of TACE on QOL. Whereas an overall QOL of patients undergoing TACE did not decline during the first 12 months after treatment (Eltawil et al., Reference Eltawil, Berry and Abdolell2012), a progressive deterioration of conditions during 24 months of observation was reported for patients after TACE (Toro et al., Reference Toro, Pulvirenti and Palermo2012). Steel and colleagues found that QOL of those who received transcatheter arterial embolization (TAE) or combined with intra-arterial chemotherapy (i.e., TACE) was lower at 3 months than pretreatment, and failed to return to baseline despite transient improvements afterwards (Steel et al., Reference Steel, Eton and Cella2006). In addition, patients who lived longer (than median survival) in this study were found to have significantly lower QOL than those who had lived less, likely resulting from greater treatment side effects (Steel et al., Reference Steel, Eton and Cella2006).
Although current evidence cannot refute TACE, there is an absence of evidence in support of its benefit to either survival or QOL for patients with unresectable HCC (Lopez et al., Reference Lopez, Villanueva and Llovet2006; Oliveri et al., Reference Oliveri, Wetterslev and Gluud2011). TACE has been suggested to be cautiously used for intermediate-stage HCC in selected candidates only (Bruix & Llovet, Reference Bruix and Llovet2002; Poon et al., Reference Poon, Fan and Tsang2002; Ramsey & Geschwind, Reference Ramsey and Geschwind2002; Llovet & Bruix, Reference Llovet and Bruix2003; Bruix et al., Reference Bruix, Sala and Llovet2004; Bruix & Sherman, Reference Bruix and Sherman2005; Reference Bruix and Sherman2011; Llovet et al., Reference Llovet, Di-Bisceglie and Bruix2008a; Raoul et al., Reference Raoul, Sangro and Forner2011; Forner et al., Reference Forner, Llovet and Bruix2012). Noticeably in China, however, TACE is recognized as the standard therapy for people with advanced HCC without correspondingly more rigorous guidelines for selection of patients or an enhanced postoperative care plan (Teo & Fock, Reference Teo and &2001; Wu et al., Reference Wu, Tang and Sun2011). Transition from initial treatment to the end of life for these patients often goes unattended and unrecognized.
NEGLECTED TRANSITION TO END-OF-LIFE
A diagnosis of advanced cancer and subsequent treatments overtaxes patient's capacities of dealing with a crisis and usually leads to increased dependence and distressing symptoms (McCorkle et al., Reference McCorkle, Benoliel and Donaldson1989; Reference McCorkle, Hughes and Robinson1998). In mainland China, discussion of palliative treatment decisions between physicians and patients usually happens only once, and on a superficial level, associated with fallacious assumptions of both healthcare providers and patients. Physicians generally assume patients want to prolong life at any cost or pain, believing that they desire a minimum positive treatment effect or tumor response at the expense of all the side-effects (Cella et al., Reference Cella, Hahn and Dineen2002; Ahmed et al., Reference Ahmed, Ahmedzai and Vora2004; Hall et al., Reference Hall, Kolliakou and Petkova2011); patients, on the other hand, trust their physicians to make the right decision, and, therefore, are willing to accept what physicians recommend (Yan & Sellick, Reference Yan and Sellick2004; Fu & Zhang, Reference Fu and Zhang2007). Consequently, emphasis has been unduly placed on patients' compliance to aggressive treatments (Dong et al., Reference Dong, Shen and Shen2009), and palliative care becomes real only at the very end of life.
Research with HCC patients has demonstrated worse QOL in terms of physical function, emotional status, and spiritual well-being despite good social and family relationships, in those patients than in people with other cancer sites (Steel et al., Reference Steel, Baum and Carr2004; Reference Steel, Eton and Cella2006; Yan & Sellick, Reference Yan and Sellick2004; Fan et al., Reference Fan, Elser and Ho2010). A longitudinal study comparing QOL in two types of hepatobiliary cancers showed that the declining trend of overall spiritual well-being in HCC patients was significantly worse than in patients with pancreatic cancer (Sun et al., Reference Sun, Ferrell and Juarez2008). This finding was supported by Yan, who compared liver and other gastrointestinal cancer patients in mainland China, and concluded that QOL of liver cancer patients was significantly the worst (Yan & Sellick, Reference Yan and Sellick2004).
There is an absence of evidence of adequate follow-up after TACE treatment in detecting recurrence or QOL maintenance for people with advanced HCC in mainland China. Regardless of higher rates of severe complications after TACE and fast progression of advanced HCC, patients are advised to make a routine follow-up clinical visit 3 months later, which is the next contact with their physicians that patients can expect after discharge. During this period of discontinuous care, distressing symptoms and rapidly deteriorating conditions usually make this disease more and more unmanageable.
LITERATURE IDENTIFICATION
A comprehensive literature review was conducted to identify and analyze promising interventions to enhance the QOL of people with advanced HCC in mainland China throughout the illness trajectory (Corbin & Strauss, Reference Corbin and Strauss1991; Robinson et al., Reference Robinson, Nuamah and Cooley1997). Outcomes were chosen to reflect overall QOL, physical, emotional, social, and functional well-being as well as psychological symptoms (such as anxiety and depression), (physical) symptom distress, and enforced social dependency. Spiritual well-being, uncertainty, and posttraumatic growth (Tedeschi & Calhoun, Reference Tedeschi and Calhoun1996), which are suggested as important for advanced cancer patients but not included in current measures for assessing QOL, were also included as outcomes for this review.
Publications were searched from 1980 to 2012 in the China Academic Journal (CAJ) database using keywords of liver cancer and quality of life in combination with randomization in abstracts. Among the 70 publications identified, 69 studies were excluded because of the pharmaceutical nature of the interventions, the focus on early stage patients, or because they were unacceptable for methodological reasons. Only one study was considered eligible (Guo, Reference Guo2005).
An extended search in CAJ was then conducted using keywords quality of life and neoplasms combined with randomization in abstracts. Of 676 identified studies, 496 focused on the effect of a drug or clinical technique; 64 targeted patients in the early stage, and 36 were not RCT. In the remaining 80 research articles, methodological issues included a lack of a control group, insufficient details about randomization, and intervention procedures. Three studies (Guo, Reference Guo2005; Li et al., Reference Li, Zhang and Fu2006; Wang et al., Reference Wang, Zhou and Ma2010) were included for the final review; however, inadequate research design and reporting prevented an accurate evaluation of these interventions (Table 1, Fig. 1).
Fig. 1. Flow diagram of the process of data extraction from the China Academic Journals database.
Table 1. Search strategy and results
aLimited in randomized controlled trial, adults (≥ 19y), year 1980–2012.
AB, in Abstract; CAJ, China Academic Journals database; TI, in Title; MeSH, Medical Subject Headings.
In order to draw upon evidence of studies from Western countries in addressing QOL for advanced cancer patients potentially generalizable to people with advanced HCC in mainland China, the search was extended to studies conducted outside mainland China. Systematic reviews were searched in the Cochrane database before searching single studies in the PubMed database using the following MeSH terms: liver neoplasms and quality of life; neoplasms and nursing (subheading); palliative care or terminal care and psychology (subheading); neoplasms and spirituality. Limitations were set at RCTs for adults, published between 1980 and 2012 (Table 1). We also hand searched the references of the retrieved articles for further relevant trials.
Initial searching found a total of 391 citations; 145 citations were excluded based on design and stage of disease. An additional 160 pharmaceutical interventions targeting survival were discarded. The remaining 86 articles were scrutinized for methodological quality as well as generalizability to HCC patients in mainland China. Fourteen articles were kept for further review. One study (Linn et al., Reference Linn, Linn and Harris1982) was identified by hand searching references. Finally, 18 studies (marked by an asterisk) in the reference list were included in the present review, including 3 RCTs conducted in mainland China (Guo, Reference Guo2005; Li et al., Reference Li, Zhang and Fu2006; Wang et al., Reference Wang, Zhou and Ma2010), 9 in the United States (Linn et al., Reference Linn, Linn and Harris1982; McCorkle et al., Reference McCorkle, Benoliel and Donaldson1989; Rummans et al., Reference Rummans, Clark and Sloan2006; Steel et al,, Reference Steel, Nadeau and Olek2007; Reference Steel, Geller and Tsung2011; Bakitas et al., Reference Bakitas, Lyons and Hegel2009; McCorkle et al., Reference McCorkle, Dowd and Ercolano2009; Breitbart et al., Reference Breitbart, Rosenfeld and Gibson2010; Reference Breitbart, Poppito and Rosenfeld2012), 1 each from the United Kingdom (Moore et al., Reference Moore, Coner and Haviland2002), Norway (Jordhøy et al., Reference Jordhøy, Fayers and Loge2001), Australia (Hudson et al., Reference Hudson, Aranda and Hayman–White2005), Japan (Ando et al., Reference Ando, Morita and Akechi2010), and Hong Kong (Lee et al., Reference Lee, Ho and Chan2010), respectively. There is also a multisite study across the United States, Canada, and Australia (Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011) (Fig. 2).
Fig. 2. Flow diagram of the process of data extraction from the PubMed database.
Overall, outcomes included physiological outcomes (e.g., survival [Linn et al., Reference Linn, Linn and Harris1982; Moore et al., Reference Moore, Coner and Haviland2002; Steel, Reference Steel, Nadeau and Olek2007; Bakitas et al., Reference Bakitas, Lyons and Hegel2009] or biological indexes [Guo, Reference Guo2005; Steel et al., Reference Steel, Nadeau and Olek2007; Reference Steel, Geller and Tsung2011]), healthcare service use and cost effectiveness (McCorkle et al., Reference McCorkle, Benoliel and Donaldson1989; Moore et al., Reference Moore, Coner and Haviland2002; Bakitas et al., Reference Bakitas, Lyons and Hegel2009), as well as psychosocial outcomes including QOL (Jordhøy et al., Reference Jordhøy, Fayers and Loge2001; Moore et al., Reference Moore, Coner and Haviland2002; Guo, Reference Guo2005; Li et al., Reference Li, Zhang and Fu2006; Rummans et al., Reference Rummans, Clark and Sloan2006; Steel et al., Reference Steel, Nadeau and Olek2007; Bakitas et al., Reference Bakitas, Lyons and Hegel2009; McCorkle et al., Reference McCorkle, Dowd and Ercolano2009; Lee et al., Reference Lee, Ho and Chan2010; Wang et al., Reference Wang, Zhou and Ma2010; Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011; Breitbart et al., Reference Breitbart, Poppito and Rosenfeld2012), life satisfaction (Linn et al., Reference Linn, Linn and Harris1982), emotional distress (Linn et al., Reference Linn, Linn and Harris1982; Hudson et al., Reference Hudson, Aranda and Hayman–White2005; Rummans et al., Reference Rummans, Clark and Sloan2006; Li et al., Reference Li, Zhang and Fu2006; Steel et al., Reference Steel, Nadeau and Olek2007; Bakitas et al., Reference Bakitas, Lyons and Hegel2009; McCorkle et al., Reference McCorkle, Dowd and Ercolano2009; Ando et al., Reference Ando, Morita and Akechi2010; Breitbart et al., Reference Breitbart, Rosenfeld and Gibson2010; Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011; Breitbart et al., Reference Breitbart, Poppito and Rosenfeld2012), symptom distress (McCorkle et al., Reference McCorkle, Benoliel and Donaldson1989; Rummans et al., Reference Rummans, Clark and Sloan2006; Bakitas et al., Reference Bakitas, Lyons and Hegel2009; McCorkle et al., Reference McCorkle, Dowd and Ercolano2009; Ando et al., Reference Ando, Morita and Akechi2010; Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011; Breitbart et al., Reference Breitbart, Poppito and Rosenfeld2012), enforced social dependency (McCorkle et al., Reference McCorkle, Benoliel and Donaldson1989; Reference McCorkle, Dowd and Ercolano2009) and disability (Linn et al., Reference Linn, Linn and Harris1982), as well as spiritual well-being (Rummans et al., Reference Rummans, Clark and Sloan2006; Ando et al., Reference Ando, Morita and Akechi2010; Breitbart et al., Reference Breitbart, Rosenfeld and Gibson2010; Reference Breitbart, Poppito and Rosenfeld2012; Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011), uncertainty (McCorkle et al., Reference McCorkle, Dowd and Ercolano2009), posttraumatic growth (Lee et al., Reference Lee, Ho and Chan2010), and dignity (Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011). Although the majority of studies focused on patients, two studies included family caregiver outcomes (Hudson et al., Reference Hudson, Aranda and Hayman–White2005; Wang et al., Reference Wang, Zhou and Ma2010).
RESULTS
The outcomes of RCTs in the oncology literature depend upon the quality of the study design and the timing of the cancer trajectory, as well as a number of moderating factors (Rehse & Pukrop, Reference Rehse and Pukrop2003). To fully understand the intervention effects and extract evidence imbedded, studies are reported with an emphasis on critical evaluation and synthesis of the current empirical evidence of promising clinical interventions on QOL and other psychosocial variables taking into account various influencing factors (Tables 2 and 3).
Table 2. Summary of studies
aStetler's level and quality of evidence. Level conveys rating per type of research, level I= Meta analysis of multiple controlled studies; level II= individual experimental study. Quality for any level ranges from A to D, and reflects basic scientific credibility of the overall study. Quality evaluation details please refer to Table 3.
bDeveloped in China.
APN, advanced practice nurse; BDI, Beck Depression Inventory; CBT, cognitive behavioral therapy; CECS, the Courtauld Emotional Control Scale; CES-D, Center for Epidemiological Studies Depression Scale; EDT, Emotional Distress Thermometer; EORTC, the European Organization for Research and Treatment of Cancers; effect size (ES), the Enforced Social Dependency Scale (ESDS), Edmonton Symptom Assessment Scale; ESDS, FACT-Hep, the Functional Assessment of Cancer Therapy—Hepatobiliary; FACIT-Pal, Functional Assessment of Chronic Illness Therapy for Palliative Care; FACIT-Sp-12, the 12 item Functional Assessment of Chronic Illness Therapy–Spiritual Well-Being; HADS, the Hospital Anxiety and Depression Scale; HCC, hepatocellular carcinoma; IES, Impact of Event Scale; LASAs, Linear Analog Scales of Assessment; McGill Quality of Life Questionnaire (MQOL), Memorial Symptom Assessment Scale (MSAS), MUIS, the Mishel Uncertainty in Illness Scale; PCLN, psychiatric consultation–liaison nurse; POMS, Profile of Mood States; POMS (SF), Profile of Mood States (Short Form); PTGI, the posttraumatic Growth Inventory; QLQ-30 RCT, randomized controlled trial; SF-36, 36-item short form health survey; SDS, Symptom Distress Scale; STAI, the State Trait Anxiety Index; TACE, transarterial chemoembolization.
Table 3. Study quality evaluation
Studies were rated on randomization, equivalence at baseline, intervention details, control details, and statistics.
0 = not done, 0.5 = not clear, 1 = clearly explained.
aAttrition here refers to measurement attrition and was calculated based on the people who were lost to follow-up regardless of treatment.
HCC, hepatocellular carcinoma; KPS, Karnofsky Performance Status; TACE, transarterial chemoembolization.
OUTCOMES REPORTED IN REVIEWED STUDIES
QOL
QOL is examined in 10 of the 18 RCTs, using either generic (McCorkle et al., Reference McCorkle, Dowd and Ercolano2009; Lee et al., Reference Lee, Ho and Chan2010; Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011), cancer-specific (Jordhøy et al., Reference Jordhøy, Fayers and Loge2001; Moore et al., Reference Moore, Coner and Haviland2002; Guo, Reference Guo2005; Li et al., Reference Li, Zhang and Fu2006; Rummans et al., Reference Rummans, Clark and Sloan2006; Wang et al., Reference Wang, Zhou and Ma2010), or site-specific QOL instruments (Steel et al., Reference Steel, Nadeau and Olek2007) or palliative care specific instruments (Bakitas et al., Reference Bakitas, Lyons and Hegel2009; Breitbart et al., Reference Breitbart, Poppito and Rosenfeld2012). All but one (Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011) of these studies used multidimensional QOL measures. Among these studies, five focused on specific cancer sites of liver (Guo, Reference Guo2005; Steel et al., Reference Steel, Nadeau and Olek2007), lung (Moore et al., Reference Moore, Coner and Haviland2002), gynecological system (McCorkle et al., Reference McCorkle, Dowd and Ercolano2009), and colorectal system (Lee et al., Reference Lee, Ho and Chan2010). Three of these interventions were psychotherapy based using meaning-centered therapy (Breitbart et al., Reference Breitbart, Poppito and Rosenfeld2012), the Eastern body–mind–spirit model (Lee et al., Reference Lee, Ho and Chan2010) or dignity therapy (Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011), whereas the others used a comprehensive approach integrating multiple self and family management components addressing QOL.
Intervention effects on QOL among groups were demonstrated in four studies (Rummans et al., Reference Rummans, Clark and Sloan2006; Bakitas et al., Reference Bakitas, Lyons and Hegel2009; McCorkle et al., Reference McCorkle, Dowd and Ercolano2009; Breitbart et al., Reference Breitbart, Poppito and Rosenfeld2012). Among them, one study on a sample of predominantly ovarian cancer patients revealed impact for the subgroup who received additional psychological intervention but not for the full sample (McCorkle et al., Reference McCorkle, Dowd and Ercolano2009); two trials showed impact for post-intervention but not for the follow-up time (Rummans et al., Reference Rummans, Clark and Sloan2006; Breitbart et al., Reference Breitbart, Poppito and Rosenfeld2012). The tailored psychosocial pilot intervention for the United States HCC patients suggested feasibility and possible clinical significance (Steel et al., Reference Steel, Nadeau and Olek2007), whereas the experiment conducted with HCC patients after TACE in mainland China showed impact on general health status only (Guo, Reference Guo2005). One study with advanced lung cancer patients in the United Kingdom showed significant results for specific symptoms and emotional well-being but not overall QOL (Moore et al., Reference Moore, Coner and Haviland2002). Three studies failed to show any benefits on QOL in comparison with controls (Jordhøy et al., Reference Jordhøy, Fayers and Loge2001; Lee et al., Reference Lee, Ho and Chan2010; Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011).
Emotional Distress
Eleven of the 18 RCTs specifically examined emotional distress (Linn et al., Reference Linn, Linn and Harris1982; Hudson et al., Reference Hudson, Aranda and Hayman–White2005; Li et al., Reference Li, Zhang and Fu2006; Rummans et al., Reference Rummans, Clark and Sloan2006; Steel et al., Reference Steel, Nadeau and Olek2007; Bakitas et al., Reference Bakitas, Lyons and Hegel2009; McCorkle et al., Reference McCorkle, Dowd and Ercolano2009; Ando et al., Reference Ando, Morita and Akechi2010; Breitbart et al., Reference Breitbart, Rosenfeld and Gibson2010; Reference Breitbart, Poppito and Rosenfeld2012; Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011) and 4 revealed intervention effects on either anxiety or depressed mood (Linn et al., Reference Linn, Linn and Harris1982; Li et al., Reference Li, Zhang and Fu2006; Bakitas et al., Reference Bakitas, Lyons and Hegel2009; Ando et al., Reference Ando, Morita and Akechi2010), observation time ranging from 2 weeks (Ando et al., Reference Ando, Morita and Akechi2010) to 3 years (Bakitas et al., Reference Bakitas, Lyons and Hegel2009). It is noted in one multidisciplinary intervention (Rummans et al., Reference Rummans, Clark and Sloan2006) for advanced cancer patients undergoing radiation treatment that whereas intervention showed benefit on emotional well-being with the Linear Analog Scales of Assessment Scale (LASAs) (Locke et al., Reference Locke, Decker and Sloan2007), emotional distress on the Profile of Mood States Scale (POMS) (Baker et al., Reference Baker, Denniston and Zabora2002) did not reveal significant difference among randomized groups.
Symptom Distress
Seven studies specifically assessed physical symptoms, using the symptom distress scale (SDS) (McCorkle & Young, Reference McCorkle and Young1978; McCorkle et al., Reference McCorkle, Benoliel and Donaldson1989; Reference McCorkle, Dowd and Ercolano2009; Rummans et al., Reference Rummans, Clark and Sloan2006) or symptom severity measures (Bakitas et al., Reference Bakitas, Lyons and Hegel2009; Ando et al., Reference Ando, Morita and Akechi2010; Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011; Breitbart et al., Reference Breitbart, Poppito and Rosenfeld2012) with varied findings. In one study with advanced stage lung cancer patients, McCorkle and colleagues (Reference McCorkle, Benoliel and Donaldson1989) demonstrated the impact of nurse-led home care intervention on symptom distress (p = 0.03) over the 6 month study period. In this study, general health and functioning also showed statistically significant difference among groups. In another longitudinal study testing nurse-administered telephone-based intervention for advanced cancer patients in rural areas, the intervention showed impact of higher QOL (p = 0.02) and lower depressed mood (p = 0.02) but not diminished symptom intensity (Bakitas et al., Reference Bakitas, Lyons and Hegel2009). One psychologist-led 7 week individual meaning-centered psychotherapy (IMCP) revealed an effect post-intervention in comparison with 7 week licensed massage (p < 0.001), which did not hold at 2 month follow-up (Breitbart et al., Reference Breitbart, Poppito and Rosenfeld2012). Rummans and colleagues in their structured comprehensive intervention for advanced cancer patients, demonstrated intervention effect on symptom reduction with the LASAs, but not the SDS (Rummans et al., Reference Rummans, Clark and Sloan2006).
Spiritual Well-Being
It has been criticized that spiritual well-being is not routinely assessed in QOL, although it takes on an important role for people with advanced cancer. Among the 18 trials, 5 examined spiritual well-being on the 12 item Functional Assessment of Chronic Illness Therapy–Spiritual Well-Being (FACIT-Sp-12) (Peterman et al., Reference Peterman, Fitchett and Brady2002) as primary outcomes. Among them, one multisite study using dignity therapy for terminally ill patients, of whom the majority were diagnosed with late stage cancer, failed to reveal significant difference between groups (Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011), whereas the majority of studies showed only short-term impact (Rummans et al., Reference Rummans, Clark and Sloan2006; Ando et al., Reference Ando, Morita and Akechi2010; Breitbart et al., Reference Breitbart, Rosenfeld and Gibson2010; Reference Breitbart, Poppito and Rosenfeld2012). For example, in two psychologist-led meaning-centered therapies for advanced cancer patients at the group and individual levels, respectively, immediate impact on patients' spiritual well-being (p = 0.009, Breitbart et al., Reference Breitbart, Rosenfeld and Gibson2010; p < 0.001, Breitbart et al., Reference Breitbart, Poppito and Rosenfeld2012) as well as the Meaning/Peace subscale (p = 0.03, Breitbart et al., Reference Breitbart, Rosenfeld and Gibson2010; p = 0.003, Breitbart et al., Reference Breitbart, Poppito and Rosenfeld2012) was shown at post-intervention; however, intervention effect ceased to be significant during the 2 month follow-up. Noticeably, despite control condition variance as well as slight difference in the duration of the intervention and sample size in these two studies, significant difference was reported among randomized groups in patients' spiritual well-being but not emotional distress.
In the structured multidisciplinary study for advanced cancer patients undergoing radiotherapy, spiritual well-being as well as overall QOL revealed significant difference only at week 4, which was the end of treatment (Rummans et al., Reference Rummans, Clark and Sloan2006). During the subsequent 5 months, whereas the intervention group maintained this level, spiritual well-being as well as QOL in the control group gradually returned to baseline. It is important to note that in this trial, the beneficial effect on the spiritual well-being from baseline to week 4 using repeated measures analysis of variance failed to reveal difference on either the LASAs or the FACIT-Sp-12.
Uncertainty and posttraumatic growth (PTG) were also extensively studied variables for people with advanced cancer. In one 6 month nurse-led home intervention for improving post-surgery outcomes of predominantly ovarian cancer patients, uncertainty showed unequivocal intervention impact between the intervention and the enhanced control groups (McCorkle et al., Reference McCorkle, Dowd and Ercolano2009). One 5 week psychotherapy intervention conducted in Hong Kong with advanced colorectal cancer patients demonstrated maintained intervention effect on posttraumatic growth (PTG) for 4 months (Lee et al., Reference Lee, Ho and Chan2010).
Family Caregivers
Cancer is a disease affecting not only the person diagnosed but also the families, who are often not adequately prepared to handle the physical and emotional needs that are inherent in cancer management (Stehlin & Beach, Reference Stehlin and Beach1966; McCorkle & Pasacreta, Reference McCorkle and Pasacreta2001). In this review, one study examined the impact of interventions on family caregivers (Wang et al., Reference Wang, Zhou and Ma2010), and one specifically designed the intervention for family caregivers (Hudson et al., Reference Hudson, Aranda and Hayman–White2005). Hudson and colleagues examined a psycho-educational intervention for family caregivers of patients dying of cancer at home in Australia. Although caregivers who received the intervention reported a significantly more positive experience than those who received standard care, indicating that it is possible to increase caregiver rewards in the midst of negative circumstances, no intervention effects were identified with respect to psychosocial variables. This might be associated with potential selection bias during recruitment resulting in unexpectedly highly functioning caregivers, disclosed by the researchers.
FACTORS POTENTIALLY INFLUENCING OUTCOMES
Intervention Delivery Mode
The majority of the interventions in this review were led by psychologists or psychiatrists (Linn et al., Reference Linn, Linn and Harris1982; Rummans et al., Reference Rummans, Clark and Sloan2006; Steel et al., Reference Steel, Nadeau and Olek2007; Reference Steel, Geller and Tsung2011; Ando et al., Reference Ando, Morita and Akechi2010; Breitbart et al., Reference Breitbart, Rosenfeld and Gibson2010; Reference Breitbart, Poppito and Rosenfeld2012; Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011), whereas eight interventions were led by nurses (McCorkle et al., Reference McCorkle, Benoliel and Donaldson1989; Reference McCorkle, Dowd and Ercolano2009; Moore et al., Reference Moore, Coner and Haviland2002; Hudson et al., Reference Hudson, Aranda and Hayman–White2005; Bakitas et al., Reference Bakitas, Lyons and Hegel2009), physicians and nurses (Jordhøy et al., Reference Jordhøy, Fayers and Loge2001; Wang et al., Reference Wang, Zhou and Ma2010), or a physician alone (Guo, Reference Guo2005). Interventions were delivered on an individual basis (Linn et al., Reference Linn, Linn and Harris1982; McCorkle et al., Reference McCorkle, Benoliel and Donaldson1989; Reference McCorkle, Dowd and Ercolano2009; Moore et al., Reference Moore, Coner and Haviland2002; Steel et al., Reference Steel, Nadeau and Olek2007; Reference Steel, Geller and Tsung2011; Bakitas et al., Reference Bakitas, Lyons and Hegel2009; Ando et al., Reference Ando, Morita and Akechi2010; Wang et al., Reference Wang, Zhou and Ma2010; Breitbart et al., Reference Breitbart, Poppito and Rosenfeld2012), in group settings (Guo, Reference Guo2005; Rummans et al., Reference Rummans, Clark and Sloan2006; Breitbart et al., Reference Breitbart, Rosenfeld and Gibson2010; Lee et al., Reference Lee, Ho and Chan2010; Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011), or cluster levels (Jordhøy et al., Reference Jordhøy, Fayers and Loge2001). It is also important to note that the majority of studies were home based (Linn et al., Reference Linn, Linn and Harris1982; McCorkle et al., Reference McCorkle, Benoliel and Donaldson1989; Reference McCorkle, Dowd and Ercolano2009; Moore et al., Reference Moore, Coner and Haviland2002; Hudson et al., Reference Hudson, Aranda and Hayman–White2005), telephone based (Bakitas et al., Reference Bakitas, Lyons and Hegel2009), or combined home visits and telephone calls (Hudson et al., Reference Hudson, Aranda and Hayman–White2005; McCorkle et al., Reference McCorkle, Dowd and Ercolano2009). Telephone calls were also used in conjunction with interventions in outpatient settings (Moore et al., Reference Moore, Coner and Haviland2002; Steel et al., Reference Steel, Nadeau and Olek2007; Reference Steel, Geller and Tsung2011).
Promising interventions to improve multiple QOL dimensions were found to be individually based and/or individually tailored, with few exceptions. For example, Ando and colleagues (Reference Ando, Morita and Akechi2010) examined the efficacy of a short-term life review for the enhancement of spiritual well-being of 68 terminally ill Japanese cancer patients. Results showed significant improvement in both spiritual well-being and psychological scores in the intervention arm (p < 0.001), indicating this short-term life review is effective and clinically relevant in improving spiritual well-being of terminally ill cancer patients and alleviating their psychosocial distress. Future research is warranted to examine whether the benefit of this life review interview to spiritual well-being could transfer to more dimensions of QOL for people with advanced cancer. On the contrary, one experiment conducted in Hong Kong, China, with 166 advanced colorectal inpatient cancer participants used group sessions of psychotherapy and this study found benefit only for PTG (p = 0.000), with no differentiation on QOL among groups (Lee et al., Reference Lee, Ho and Chan2010).
Rummans and colleagues (Reference Rummans, Clark and Sloan2006) conducted a structured intervention containing eight 90-minute sessions for advanced cancer patients during radiotherapy with intervention effect shown at the end of treatment (also the end of 4 weeks of radiotherapy). Whereas the main body of the intervention was based on group sessions led by a psychiatrist or psychologist, further support from multidisciplinary team was on an individual level. Another study with HCC after TACE in mainland China used group sessions for weekly psychoeducational intervention; however, the Chinese medicated diet was individually tailored (Guo, Reference Guo2005). Similarly, in a multisite dignity psychotherapy, sessions were designed at the group level; however, the content was individually tailored, accommodating the participant's preferences and choices (Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011). This study failed to show intervention effect among groups on dignity, spiritual well-being, or QOL, potentially attributed to the competing control groups.
Timing of Interventions
Timing of interventions for advanced cancer patients varied, ranging from during the perioperative period (Moore et al., Reference Moore, Coner and Haviland2002; Guo, Reference Guo2005; McCorkle et al., Reference McCorkle, Dowd and Ercolano2009), to while undergoing or between radiation or chemotherapies (Rummans et al., Reference Rummans, Clark and Sloan2006; Steel et al., Reference Steel, Nadeau and Olek2007; Reference Steel, Geller and Tsung2011), to while receiving end-of-life palliative care service (Linn et al., Reference Linn, Linn and Harris1982; Jordhøy et al., Reference Jordhøy, Fayers and Loge2001; Li et al., Reference Li, Zhang and Fu2006; Bakitas et al., Reference Bakitas, Lyons and Hegel2009; Ando et al., Reference Ando, Morita and Akechi2010; Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011), whereas the time frame with respect to diagnosis was only clearly documented in two studies (McCorkle et al., Reference McCorkle, Benoliel and Donaldson1989; Bakitas et al., Reference Bakitas, Lyons and Hegel2009).
Intervention Type and Components
Six of the 18 RCTs selected a single component of psychosocial methods such as psychotherapy (Ando et al., Reference Ando, Morita and Akechi2010; Lee et al., Reference Lee, Ho and Chan2010), counseling (Linn et al., Reference Linn, Linn and Harris1982), dignity therapy (Chochinov et al., Reference Chochinov, Kristjanson and Breitbart2011), or meaning-based logotherapy (Breitbart et al., Reference Breitbart, Rosenfeld and Gibson2010; Reference Breitbart, Poppito and Rosenfeld2012), whereas the others used a comprehensive approach containing clinical assessments, complication monitoring, teaching self-management skills, and coordinating resources for patients' ongoing needs as well as treatment decision-making assistance and direct care (McCorkle et al., Reference McCorkle, Benoliel and Donaldson1989; Reference McCorkle, Dowd and Ercolano2009; Jordhøy et al., Reference Jordhøy, Fayers and Loge2001; Moore et al., Reference Moore, Coner and Haviland2002; Guo, Reference Guo2005; Hudson et al., Reference Hudson, Aranda and Hayman–White2005; Li et al., Reference Li, Zhang and Fu2006; Steel et al., Reference Steel, Nadeau and Olek2007; Reference Steel, Geller and Tsung2011;Bakitas et al., Reference Bakitas, Lyons and Hegel2009; Wang et al., Reference Wang, Zhou and Ma2010).
The pilot trial with HCC patients in the United States reported by Steel and colleagues (Reference Steel, Nadeau and Olek2007) deserves to be mentioned. In this individually tailored intervention, a combination of education, cognitive-behavioral therapy, and supportive-expressive therapy was delivered either in person or via phone (depending upon whether patients were undergoing treatments or were between treatments) to 28 hepatobiliary participants (among them 23 were HCC patients). Clinically although not statistically significant improvements of symptoms of depression and anxiety, and disease-related symptoms were shown for people randomized to the intervention arm who reported a minimally important difference (MID) (Cella et al., Reference Cella, Hahn and Dineen2002) for emotional well-being, albeit with decrements in physical and functional well-being. However, the control group receiving only education also showed MID.
Education as the basic level of a psychosocial intervention (Cunningham, Reference Cunningham2002; Rehse & Pukrop, Reference Rehse and Pukrop2003) has been integrated in most studies to improve patients' and families' outcomes across acute (Guo, Reference Guo2005), unstable (Rummans et al., Reference Rummans, Clark and Sloan2006), downward (McCorkle et al., Reference McCorkle, Benoliel and Donaldson1989; Reference McCorkle, Dowd and Ercolano2009; Moore et al., Reference Moore, Coner and Haviland2002; Steel et al., Reference Steel, Nadeau and Olek2007; Reference Steel, Geller and Tsung2011; Bakitas et al., Reference Bakitas, Lyons and Hegel2009), and dying phases (Hudson et al., Reference Hudson, Aranda and Hayman–White2005; Li et al., Reference Li, Zhang and Fu2006). However, one remarkable characteristic of nurse-led interventions (McCorkle et al., Reference McCorkle, Benoliel and Donaldson1989; Reference McCorkle, Dowd and Ercolano2009; Moore et al., Reference Moore, Coner and Haviland2002; Hudson et al., Reference Hudson, Aranda and Hayman–White2005; Bakitas et al., Reference Bakitas, Lyons and Hegel2009) that emerged in this review for advanced cancer patients was symptom management.
Wang and colleagues (Reference Wang, Zhou and Ma2010) reported home care services in mainland China for cancer patients and their families. The intervention consisted of symptom monitoring, pain management, functional rehabilitation, nutritional guidance, and psychological as well as social support to both patients and families. Significant differences were found in patients' fatigue, nausea and vomiting, somnipathy, anepithymia, constipation, diarrhea, and overall QOL in comparison with the control group (p < 0.01); better QOL was also reported in families (p < 0.01). Results however have to be interpreted with caution because of insufficient details of the randomization process.
McCorkle and colleagues (Reference McCorkle, Benoliel and Donaldson1989) examined the effect of comprehensive home nursing service early in lung cancer patients' trajectory on distressing symptoms, functional status, health perceptions, and psychosocial concerns. Their intervention involved nursing care in symptom management, cancer coordination, appropriate referral, and team building. Results showed that home nursing care groups run by either oncology nurse specialists or interdisciplinary teams had less distress (p = 0.03) and greater independence 6 weeks longer (p = 0.02) albeit worse health perceptions (p < 0.05) than traditional care groups provided by physicians; no differences in pain, mood disturbance, or concerns were found between the intervention and control groups. This indicates that home nursing care may assist patients with forestalling distress from symptoms, maintaining longer independence, and holding realistic health perceptions congruent with their physical conditions.
This nurse-led comprehensive home care intervention was further tested in a sample of postsurgical women with gynecological cancers (McCorkle et al., Reference McCorkle, Dowd and Ercolano2009). In addition to clinical assessments, complication monitoring, teaching self-management skills, and coordinating resources by advanced practice nurse (APN) for patients' ongoing needs, a consultative psychiatric liaison nurse was added for additional psychological support. Results showed that the intervention group, particularly the subgroup receiving the tailored psychological support had less uncertainty, (p = 0.02) less symptom distress (p < 0.0001) and better QOL (p ≤ 0.0001), which demonstrated the effects of this tailored intervention based on the standard nursing intervention protocol (SNIP) in improving QOL outcomes for people with advanced cancer (McCorkle et al., Reference McCorkle, Strumpf and Nuamah2000).
Concerns about the lack of continuity of care for postoperative cancer patients were also revealed in the study by Moore and colleagues (Reference Moore, Coner and Haviland2002). This study assessed the effectiveness of nurse-led follow-up for lung cancer patients who had completed initial treatment in comparison with conventional medical follow up in the United Kingdom. Clinical nurse specialists provided information and support monthly over the phone or in a clinic, and coordinated with other agencies or services. Compared with conventional medical follow-up, the intervention arm achieved less severe dyspnea at 3 months (p = 0.03), better emotional functioning (p = 0.03), and less peripheral neuropathy at 12 months (p = 0.05).
Bakitas and colleagues (Reference Bakitas, Lyons and Hegel2009) tested the effectiveness of APN-administered telephone-based intensive and ongoing assessment and coaching to 322 advanced cancer patients living in rural areas. Specifically, the intervention included symptom management, advance directive planning and treatment decision making, with an emphasis on communicating during anticancer treatments. The intervention also involved teaching patients and families to improve coping and problem-solving skills. This 3 year study revealed an intervention effect on improved QOL (the Functional Assessment of Chronic Illness Therapy for Palliative Care or FACIT-Pal, p = 0.02) (Lyons et al., Reference Lyons, Bakitas and Hegel2009) and lower depressed mood (Center for Epidemiological Studies Depression Scale or CES-D, p = 0.02) (Okun et al., Reference Okun, Stein and Bauman1996). Symptom intensity measured with the Edmonton Symptom Assessment Scale (ESAS) (Bruera et al., Reference Bruera, Kuehn and Miller1991) was not significantly different between groups.
Control Condition
It is important to point out that intervention effect is context dependent, and results of intervention have to be interpreted in light of the context in which they were obtained, as changes in setting or point in time or a more homogeneous sample might produce different findings (Jordhøy et al., Reference Jordhøy, Fayers and Loge2001).
The study conducted in Norway assessing the impact of multidisciplinary palliative care interventions at hospital and community levels to advanced cancer patients included systematic assessment of multiple domains of QOL by trained staff and coordinated follow-up by general practitioners and community nurses, but no significant difference was found in comparison with standard care (Jordhøy et al., Reference Jordhøy, Fayers and Loge2001).
Li and colleagues (Reference Li, Zhang and Fu2006) conducted a 1 month comprehensive team intervention by surgeons, physicians, and nurses for 76 terminally ill cancer patients and their families in palliative care units of mainland China. The intervention included death education, pain relief, psychosocial support, and nutritional and other palliative therapies; the control group received usual care and was described as “[holistic care];” however, no criteria or necessary specific details were provided for the control condition. Although QOL and other indexes showed significant differences between groups (p < 0.05), it is difficult to interpret the results in comparison with the control group, could be identified to determine how it differed from those receiving usual care.
Only one non-pharmaceutical intervention for people diagnosed with HCC in mainland China designed by Guo (Reference Guo2005) deserves to be mentioned. This experiment involved an emotional intervention combined with Chinese medicated diet after TACE, while patients remained in the hospital. Specifically, patients were taught about treatments they were receiving, prognosis of the disease, relaxation via music, or meditation; Chinese medicated diet contained traditional Chinese medicine, tailored to the individual's physical condition, adjuvant with the treatments. After 2 months, the intervention arm showed significantly improved symptoms of fatigue, nausea, emesis, anorexia, and overall QOL (p < 0.05) as well as liver biological indexes (p < 0.01).
The results of this study have to be viewed with caution. First, the author who administered the interventions and also assessed the outcomes was not blinded to group assignment. Second, details about randomization and intervention procedures as well as effort of eliminating possible confounding factors were unable to be identified, making it difficult to interpret the results. Furthermore, as the time length of hospitalization after TACE in mainland China varied but generally within ≤ 2 weeks, making translating this 2 month intervention into practice problematic.
LIMITATIONS
Several limitations of this review should be noted. First, studies were reviewed based on CONSORT guidelines for randomized controlled trials (Boutron et al., Reference Boutron, Moher and Altman2008; Schulz et al., Reference Schulz, Altman and Moher2010) and graded using Stetler's level and quality of evidence (Stetler et al., Reference Stetler, Morsi and Rucki1998); evidence might have been further strengthened if all the reviewed studies had provided effect size and power analysis. In addition, the studies reviewed varied in sample homogeneity and attrition rates, as well as instruments selected for targeted outcomes, making interpretation of findings and comparison among studies difficult, if even possible.
Another limitation was associated with the unique challenge imposed by the specific population of interest. Studies for HCC in mainland China are underrepresented in this review because of a general lack of critical details required for reporting of RCT (Boutron et al., Reference Boutron, Moher and Altman2008), which precluded appraisal of studies on HCC in more detail. The setting was uniformly selected in tertiary, academic hospitals or urban communities, making generalization of findings with respect to rural areas questionable. For intervention components, few studies provided sufficient description of the procedure for tailoring the interventions to individual participants; for controls, there was generally no description of the care that the control group received, and regarding the intervention group, the number of sessions, timing of each session, duration of each session, duration of each main component of each session, and overall duration of the intervention were seldom described. In clinical practice in mainland China, social workers, chaplains, and psychologists are seldom involved, and the training needed for the professionals implementing the trials was not documented in either intervention or control groups.
Because of scant evidence for people diagnosed with advanced HCC in mainland China, we have extended our searching to advanced cancer patients in general as well as rigorously designed studies that show promise in the West. This evidence derived from the West might be argued to be not generalizable to a population in another country. It is important to note, however, that this generalization limitation poses challenges not for the current review alone; effective translation of research evidence outside the original setting is always a concern (Kirchhoff, Reference Kirchhoff2004). Intervention effectiveness is not only associated with population and setting, but also the interaction of the intervention with subjects and context; and the latter can be hard to control even for studies conducted within the same culture and the same type of healthcare systems.
Finally, despite the comprehensive inclusion of PubMed and CAJ, search using these two databases may not be exhaustive for retrieving studies from the Western and Chinese literature, and further expansion is warranted.
CONCLUSIONS
HCC remains one of the most highly lethal cancers in the world. Ongoing close attention to the unique physiological and psychosocial concerns is crucial for the remaining QOL of people with advanced HCC throughout their cancer trajectory. Timely assessment and evaluation of symptoms present a particular challenge for people with HCC in mainland China, as the lack of standardization in treatment methodology and patient selection of TACE (Raoul et al., Reference Raoul, Sangro and Forner2011) exacerbates the need of intensified monitoring of patients after this treatment. Moreover, most people are treated at tertiary care centers where they visit infrequently and travel long distances for evaluation and treatment, and this may have further restrained access to already limited resources.
In mainland China, in spite of the necessity of intensive follow-up for postoperative cancer patients after discharge (McCorkle et al., Reference McCorkle, Strumpf and Nuamah2000), effort has been largely limited to the perioperative period during hospitalization, and people with advanced HCC are confronted with a quickly progressive disease, limited treatment options, and inadequate care. Most patients enter a downward and dying phase soon after being discharged from the hospital. The time from discharge to the end of life is neglected. This review confirms and extends the findings of earlier work that education and psychosocial support combined with symptom management early in the illness trajectory may improve multiple domains of QOL for these patients. Nurse-led home-based comprehensive intervention delivered for postoperative follow-up either by telephone or face-to-face contact is most promising to improve QOL for people with advanced cancer in general and HCC in particular. The complex interplay of physical, psychological, social, and spiritual burdens experienced by these patients makes it paramount that interventions be designed using a collaborative care approach and conducted with the aim of providing comprehensive care to address multiple dimensions of QOL (Milone-Nuzzo & McCorkle, Reference Milone-Nuzzo, McCorkle, Ferrell and Coyle2001; Sun et al., Reference Sun, Ferrell and Juarez2008; Zimmermann et al., Reference Zimmermann, Riechelmann and Krzyzanowska2008; Fielding, Reference Fielding, Holland, Breitbart and Jacobsen2010).
One of the challenges for researchers in Eastern countries is how to appreciate and use evidence from the West. This generalization gap in geographic borderlines should not be overemphasized, as culture is only one of all those factors that could modify the intervention effect and there is no clear evidence of the impact of culture in determination of the intervention effect. There is little evidence, however, that strategies working well in Western countries will be as effective in mainland China, especially when insufficient data prevent making reasonable comparisons between the East and West (Wu et al., Reference Wu, Dugoua and Eyawo2009). It is, therefore, warranted that promising clinical interventions aimed to improve quality of life for advanced cancer patients reported in Western literature be further tested in mainland China.
ACKNOWLEDGMENT
This study was supported by a grant from the National Institutes of Health (NIH) and the National Institutes of Nursing Research (NINR) through the Research Project Grant (R01) (Grant number NR011872, to Dr. McCorkle).
