Review on Quality of Life Issues in Patients with Primary Brain Tumors

Health‐related quality of life (HRQOL) has become an important outcome measure in clinical trials in primary brain tumor (i.e., glioma) patients, because they have an incurable disease. HRQOL is assessed using self‐reported, validated questionnaires, addressing physical, psychological, emotional, and social issues. In addition to generic HRQOL instruments, disease‐specific questionnaires have been developed, including for brain tumor patients. For the analysis and interpretation of HRQOL measurements, low compliance and missing data are methodological challenges. HRQOL in glioma patients may be negatively affected by the disease itself as well as by side effects of treatment. But treatment with surgery, radiotherapy, and chemotherapy may improve patient functioning and HRQOL, in addition to extending survival. Although HRQOL has prognostic significance in brain tumor patients, it is not superior to well‐known clinical parameters, such as age and performance status. In clinical practice, assessing HRQOL may be helpful in the communication between doctor and patient and may facilitate treatment decisions.     

Health-related quality of life in patients undergoing drug therapy for advanced non-small-cell lung cancer

Health-related quality of life (HRQoL) is increasingly recognized as an important outcome in the treatment of advanced non-small-cell lung cancer (NSCLC). This article reviews HRQoL data from a literature search that identified 32 randomized trials of conventional chemotherapy in patients with advanced NSCLC. In common with much of the research in this area, interpretation of the data from some trials was limited by weaknesses in data collection and reporting of HRQoL results. Nevertheless, the trials comparing chemotherapy with best supportive care consistently identified that some components of HRQoL improved with chemotherapy, despite the associated toxicity of many of the regimens used. Novel targeted therapies promise efficacy without the toxicity typically observed with conventional chemotherapy, and this article also reviews HRQoL data from trials of gefitinib (IRESSA), the first epidermal growth factor receptor tyrosine kinase inhibitor to have demonstrated prospectively defined, clinically meaningful improvements in disease-related symptoms and HRQoL in patients with advanced NSCLC. In all trials reviewed, HRQoL findings to date support the incorporation of well-validated measures of HRQoL and symptom improvement in all future trials of drug therapy in advanced NSCLC patients. Ideally, the trials should have a prospectively defined HRQoL hypothesis, include measures to improve compliance with HRQoL assessments, and address the clinical meaning of the HRQoL findings.     

Challenging the current norm: Does health related quality of life data from reference populations accurately reflect baseline values in breast cancer patients? An observational cohort study comparing EORTC QLQ-C30 scores between the general Swedish population and baseline scores in breast cancer patients

BackgroundIncreased overall survival in breast cancer patients has led to a growing recognition of long-term effects of cancer treatment of patients’ quality of life. Health related quality of life (HRQoL) data, as measured by patient reported outcome measures (PROMs), is increasingly incorporated into clinical practice and research. A commonly used method current available to interpret HRQoL PROMs data is by comparison to reference values, often obtained from sampling of the general population. The aim of this study was to assess whether HRQoL reference values derived from the general population are an accurate representation of the baseline values of an outpatient breast clinic population.MethodsA prospective observational cohort study was conducted by obtaining EORTC QLQ-C30 values for all patients offered an appointment in the outpatient breast clinic. These results were then compared to published baseline values in the general Swedish population, matched by gender and age.Results568 questionnaires were returned with a response rate of 81,1 %. The outpatient breast clinic cohort reported a higher grade of symptoms, lower function and lower quality of life compared to the equivalent reference population.ConclusionThis study challenges the assumption that the reference values accurately reflect those of the study population which clinicians and researchers need to account for in study design and clinical practice.     

Health-related quality-of-life as co-primary endpoint in randomized clinical trials in oncology

Overall survival (OS) has been considered as the most relevant primary endpoint but trials using OS often require large numbers of patients and long-term follow-up. Therefore composite endpoints, which are assessed earlier, are frequently used as primary endpoint but suffer from important limitations specially a lack of validation as surrogate of OS. Therefore, Health-related quality of life (HRQoL) could be considered as an outcome to judge efficacy of a treatment. An alternative approach would be to combine HRQoL with composite endpoints as co-primary endpoint to ensure a clinical benefit for patients of a new therapy. The decision rules of such design, the procedure to control the Type I error and the determination of sample size remain questions to debate. Here, we discusses HRQoL as co-primary endpoints in randomized clinical trials in oncology and provide some solutions to promote such design.     

Measurement of quality of life in clinical trials.

Information on patients' quality of life (QOL) will give a more comprehensive evaluation of the treatment outcome than only measures of tumour response and survival. Psychosocial indicators have rarely been used in clinical trials. This may in part be explained by physicians' lack of familiarity with these measures, methodological insufficiency and a basic philosophical reason, i.e., most doctors tend to focus on curative treatment and not on palliative treatment. A series of QOL questionnaires has been validated in the last decade for use in cancer clinical trials. Selection of the optimal method in the given trial is important. The trial ought to be designed so the proportion of missing data is low. QOL should be used as an end point in selective trials with an optimal study design and with a study coordinator who is willing to collect QOL data.     

How health-related quality of life assessment should be used in advanced colorectal cancer clinical trials

Traditionally, the efficacy of cancer treatment in patients with advance or metastatic disease in clinical studies has been studied using overall survival and more recently tumor-based end points such as progression-free survival, measurements of response to treatment. However, these seem not to be the relevant clinical end points in current situation if such end points were no validated as surrogate of overall survival to demonstrate the clinical efficacy. Appropriate, meaningful, primary patient-oriented and patient-reported end points that adequately measure the effects of new therapeutic interventions are then crucial for the advancement of clinical research in metastatic colorectal cancer to complement the results of tumor-based end points. Health-related quality of life (HRQoL) is effectively an evaluation of quality of life and its relationship with health over time. HRQoL includes the patient report at least of the way a disease or its treatment affects its physical, emotional and social well-being. Over the past few years, several phase III trials in a variety of solid cancers have assessed the incremental value of HRQoL in addition to the traditional end points of tumor response and survival results. HRQoL could provide not only complementary clinical data to the primary outcomes, but also more precise predictive and prognostic value. This end point is useful for both clinicians and patients in order to achieve the dogma of precision medicine. The present article examines the use of HRQoL in phase III metastatic colorectal cancer clinical trials, outlines the importance of HRQoL assessment methods, analysis, and results presentation. Moreover, it discusses the relevance of including HRQoL as a primary/co-primary end point to support the progression-free survival results and to assess efficacy of treatment in the advanced disease setting.     

Quality of life versus prolongation of life in patients treated with chemotherapy in advanced colorectal cancer: A review of randomized controlled clinical trials

Oncologists disagree if chemotherapy in advanced cancer can improve quality of life (QoL), to prolong duration of life, or both. The objective of this study was to clarify the main treatment intention of palliative chemotherapy (PCT): the prolongation of life (PoL); or QoL. Randomized controlled clinical trials of PCT in advanced colorectal cancer that included HRQoL assessment were selected from PubMed and reviewed. Authors' conclusions were based on both PoL- and QoL-related outcomes. However, if PoL and QoL outcomes of the experimental arm were opposite, which was the case in 13 out of 28 trials, the authors generally based their conclusion on PoL outcomes. Authors' conclusions focused mainly on PoL-related outcomes, while QoL-related outcomes were of overriding importance in only 1/28 case. QoL can therefore not be considered as the main outcome of PCT. The review shows that in the context of chemotherapy in advanced colorectal cancer, 'palliative' refers to a life-prolonging intention, whereas within palliative care it refers to an improvement in QoL.     

Evaluating the health-related quality of life of esophageal cancer patients

The current norm of esophageal treatment includes any combination of surgery, chemotherapy and radiation therapy. The effectiveness of medical intervention has been predominantly assessed by morbidity, mortality and disease-free survival in the past. As patients' life expectancies lengthened from advances in treatment modalities, recent movements have shifted to acknowledge patients' health-related quality of life as an important outcome measure. The general trend for the use of multimodal treatments of esophageal cancer indicates an initial degradation of many aspects of HRQoL; however, without postoperative recovery delay related to neoadjuvant treatment. Several recent studies aimed to define aspects of HRQoL as prognostic indicators of esophageal cancer patients that may influence survival. It is imperative for practicing physicians to discuss these concepts with patients as they may cope with treatment complications more favorably if they are informed.     

Factors associated with health-related quality of life (HRQoL) deterioration in glioma patients during the progression-free survival period

BackgroundMaintenance of functioning and well-being during the progression-free survival (PFS) period is important for glioma patients. This study aimed to determine whether health-related quality of life (HRQoL) can be maintained during progression-free time, and factors associated with HRQoL deterioration in this period.MethodsWe included longitudinal HRQoL data from previously published clinical trials in glioma. The percentage of patients with stable HRQoL until progression was determined per scale and at the individual patient level (i.e. considering all scales simultaneously). We assessed time to a clinically relevant deterioration in HRQoL, expressed in deterioration-free survival and time-to-deterioration (the first including progression as an event). We also determined the association between sociodemographic and clinical factors and HRQoL deterioration in the progression-free period.ResultsFive thousand five hundred and thirty-nine patients with at least baseline HRQoL scores had a median time from randomization to progression of 7.6 months. Between 9–29% of the patients deteriorated before disease progression on the evaluated HRQoL scales. When considering all scales simultaneously, 47% of patients deteriorated on ≥1 scale. Median deterioration-free survival period ranged between 3.8–5.4 months, and median time-to-deterioration between 8.2–11.9 months. For most scales, only poor performance status was independently associated with clinically relevant HRQoL deterioration in the progression-free period.ConclusionsHRQoL was maintained in only 53% of patients in their progression-free period, and treatment was not independently associated with this deterioration in HRQoL. Routine monitoring of the patients’ functioning and well-being during the entire disease course is therefore important, so that interventions can be initiated when problems are signaled.     

Assessment of quality of life during chemotherapy.

Increasingly more aggressive chemotherapy together with expected small differences between treatments with respect to objective endpoints has heightened awareness about the importance of addressing how patients experience and value the impact that treatment has had on their overall life situation. Assessment of a patient's quality of life (QoL) is now conceptually viewed as an important complement to traditional objective evaluation measures. It was therefore considered important to review the basis for the assessment of this endpoint when The Swedish Council of Technology Assessment in Health Care (SBU) performed a systematic overview of chemotherapy effects in several tumour types. The group came to the following conclusions: QoL assessments, mostly by patient self-reporting in questionnaires, have come increasingly into use during the past decade. A number of general, cancer-specific and cancer diagnosis-specific instruments have been developed. There is at present little need for development of new cancer instruments, although specific treatment modalities and tumour types may need new additional modules. A predefined hypothesis should determine the instrument to be used. Since the selection of a QoL instrument in a specific study influences both the results and the conclusions, it is essential to carefully select the instrument or instruments that have the greatest likelihood of identifying relevant differences between treatment alternatives. Interpretation of QoL data is more difficult than interpretation of objective endpoints such as survival time, objective response rates or toxicity. Despite these difficulties, QoL analyses have provided new insights into the advantages and disadvantages of various treatments not provided by traditional end-points. Some palliative treatments seemingly increase patients' QoL despite side-effects or the lack of, or marginal, increases in survival. When using potentially curative chemotherapy, it is not a matter of when the treatment should be started, but rather when it should be concluded. When using less active chemotherapy, the expected small therapeutic gains must be weighed against the QoL costs of using the therapy: does the toxicity and/or the inconvenience of the proposed treatment justify the expected gain? When it is found that the strain on the patient is greater than the effects of the cancer, treatment must be discontinued. It is not possible to determine whether or not the advantages of palliative chemotherapy are worth their costs without knowledge about patients' personal values regarding the influence on factors of relevance for QoL. The mostly used QoL questionnaires do not consider individual preferences, which therefore need to be addressed in the dialogue with the patient. QoL assessment is clearly in need of further methodological improvement before this endpoint can be regarded as fully established with respect to ability to provide unequivocally useful data in clinical trials. The multitude of questionnaires, missing data, lack of pre-study hypotheses of relevant differences between treatments and data multiplicity giving a risk for chance findings are examples of serious methodological problems. Patient response-shifts over time further complicate the interpretation of the data. Thus, QoL data, also from seemingly well-performed clinical trials, have to be interpreted cautiously. The international development during recent years has aimed at creating increased standardization of QoL measures. This has created greater possibilities to compare results from different trials. Hopefully, this also implies that it will be possible to draw firmer conclusions from QoL measurements in recently completed or ongoing trials than has been the case previously. QoL assessments are resource demanding even when short standardized questionnaires are used. Since cancer patients also generally give priority to anticancer effects over toxicity and convenience, QoL assessments in clinical trials are motivated mainly in study settings comparing treatments without expected major differences of outcome in objective endpoints.     

Quality of life and supportive care for patients with metastatic renal cell carcinoma

In recent years, a key issue in the management of patients with metastatic renal cell carcinoma (mRCC) has been the assessment of health-related quality of life (HRQoL), particularly following the introduction of targeted therapies that have brought significant improvements in progression-free survival and quality of life in these patients. HRQoL is becoming one of the main factors influencing choice of therapy, and HRQoL experienced during first-line treatment may affect the choice of the second-line therapy. Consequently, several trials have been conducted to evaluate the impact of approved targeted therapies for mRCC on HRQoL, and this measure is being introduced with increasing frequency in the trial design. With respect to agents used after progression on cytokines, sunitinib and temsirolimus have yielded better HRQoL scores, and sorafenib and pazopanib have shown stable HRQoL scores compared with placebo. Regarding targeted agents approved for patients who progress on a first-line tyrosine kinase inhibitor, everolimus has shown to delay and reduce the degree of Karnofsky performance status deterioration compared with placebo. Moreover, evidence obtained from these trials shows that tumor response and delay in disease progression affect HRQoL. In this article, we review the different HRQoL scales used to evaluate patients with mRCC along with the results obtained in clinical trials. Given that HRQoL is determined not only by treatment-related effects but also by mRCC symptoms and its clinical complications, the characteristics and appropriate treatment of the most commonly experienced symptoms, including anorexia, fatigue, pain, anemia, and venous thromboembolism, are also reviewed.     

Preserving quality of life as a key treatment goal in advanced soft tissue sarcomas

Introduction: Health-related quality of life (HRQoL) is a patient-reported outcome that addresses patients’ perceptions of symptoms across physical, emotional, cognitive and social domains. As HRQoL is currently rarely measured outside clinical trials in oncology, it must be inferred from patients’ everyday performance during treatment. To gain insight into the HRQoL of advanced STS patients receiving palliative treatment in clinical practice, three case studies of patients treated with trabectedin are examined.

Areas covered: The patient in Case 1 has maintained complete remission for more than 8 years after receiving nine cycles of second-line trabectedin followed by secondary surgery for recurrent myxoid liposarcoma, and was able to resume normal activities during trabectedin treatment. Case 2 describes 10 years’ follow-up of a patient with myxoid liposarcoma who remains well after many lines of chemotherapy including extended use of trabectedin in the second line. The third case illustrates the feasibility of extending survival time in an elderly patient with metastatic leiomyosarcoma who was able to maintain a busy and active lifestyle while receiving second-line trabectedin.

Expert commentary: Owing to its relatively benign safety profile, trabectedin frequently permits prolonged therapy and is generally well tolerated, often allowing patients to carry on with normal daily activities.     

Health-Related Quality of Life in EORTC clinical trials — 30 years of progress from methodological developments to making a real impact on oncology practice

The impact of cancer on patients' lives can be measured using self-reported questionnaires, known as Health-Related Quality of Life (HRQOL) measures. HRQOL is defined as a multi-dimensional construct covering disease and treatment-related symptoms, physical, psychological, and social functioning.The EORTC Quality of Life Group (QLG) was created in 1984 with the mission to develop measures of HRQOL and to promote and coordinate clinical studies concerning the quality of life of cancer patients. The EORTC Quality of Life Department (QL Department) was founded in 1993 with the support of an EU grant to provide administrative, practical and scientific support to co-operative groups conducting clinical trials with HRQOL outcomes.We are proud to report significant scientific achievements that have made us international leaders in HRQOL research and have led to real changes to cancer patient treatments.We developed a modular system for HRQOL measurement consisting of the EORTC QLQ-C30, a core cancer quality of life questionnaire and supplementary questionnaire modules. The EORTC-QLQ-C30 has been one of the most widely used cancer questionnaires in randomized trials in oncology as demonstrated by systematic reviews. To date, the EORTC QLQ-C30 has been translated and linguistically validated into more than 60 languages.HRQOL outcome measures have been an integral part of EORTC clinical trials for the last 30 years. We present examples of significant, practice-changing clinical trials evaluating HRQOL in several cancer sites, such as brain tumors, breast and ovarian cancers, and malignant melanoma. In a series of systematic reviews, we examined the quality of reporting HRQOL in international cancer clinical trials, and the impact of the results on oncology practice that led to a recommendation to improve CONSORT (Consolidated Standards of Reporting Trials) with regard to reporting of HRQOL.The QLG is an international leader in methodological research in the measurement of HRQOL in oncology and pursues research in several key areas, such as cross-cultural differences between populations in HRQOL assessment, Computer-Adaptive Testing, electronic administration of EORTC QLQ-C30, and summary scores for EORTC QLQ-C30.In summary, the QLG and QL Department have been international leaders in the field. Our questionnaires have brought HRQOL assessment to the fore in many international trials that have changed oncology practice and brought the patient's perspective into cancer research.     

Perceptions of patients and physicians regarding phase I cancer clinical trials: implications for physician-patient communication.

PURPOSE: To describe and compare the perceptions of cancer patients and their physicians regarding phase I clinical trials. METHODS: Eligible patients had been offered phase I trial participation and had decided to participate but had not yet begun treatment. Each patient's physician also served as a study subject. Patients and physicians completed questionnaires with domains including perceptions of potential benefit and harm from treatment (experimental and standard), relative value of quality and length of life, and perceived content of patient-physician consultations. RESULTS: Three hundred twenty-eight patients and 48 physicians completed surveys. Patients had high expectations regarding treatment outcomes (eg, median 60% benefit from experimental therapy), with those choosing to participate in a phase I trial being more optimistic than those declining phase I participation. Patients predicted a higher likelihood of both benefit and adverse reactions from treatment (experimental and standard) than their physicians (P <.0001 for all comparisons). Although 95% of patients reported that quality of life was at least as important as length of life, only 28% reported that changes in quality of life with treatment were discussed with their physicians. In contrast, 73% of physicians reported that this topic was discussed (P <.0001). CONCLUSION: Cancer patients offered phase I trial participation have expectations for treatment benefit that exceed those of their physicians. The discordant perceptions of patients and physicians may possibly be explained by patient optimism and confidence; however, the discrepancies in reports of consultation content, particularly given patients' stated values regarding quality of life, raise the possibility that communication in this context is suboptimal.     

Impact of quality of life on patient expectations regarding phase I clinical trials.

PURPOSE: Quality of life (QOL) is increasingly recognized as a critical cancer-treatment outcome measure, but little is known about the impact of QOL on the patient decision-making process. A pilot study was conducted in an effort to (1) measure the expectations of patients, physicians, and research nurses regarding the potential benefits and toxicities from experimental and standard therapies, and (2) determine the relationship of QOL to patient perceptions regarding treatment options. METHODS: Thirty cancer patients enrolling in phase I clinical trials, their physicians, and their research nurses were administered questionnaires that assessed demographics, QOL, and treatment expectations. RESULTS: Compared with their physicians, patients overestimated potential benefits and toxicities from experimental therapy (mean expected benefit, 59.8% v 23.8%, P <.01; mean expected toxicity, 29.8% v 16.0%, P <.01). Patients estimated a greater potential for benefit (59.8% v 36.8%, P <.01) and less potential for toxicity (29.8% v 45.6%, P =.01) for experimental therapy, compared with standard therapy. Short Form-36 general health perception correlated with patient perception of potential benefit from experimental therapy (r =.48, P =.01). CONCLUSION: Participants in phase I clinical trial have high expectations regarding the success of experimental therapy and discount potential toxicity. Patient QOL may affect the expectation of benefit from experimental therapy and, ultimately, treatment choice. Understanding the interactions between QOL and patient expectations may guide the development of improved strategies to present appropriate information to patients considering early-phase clinical trials.     

Post-treatment surveillance in colorectal cancer

BACKGROUND: Though the post treatment surveillance of patients with colorectal cancer (CRC) treated with curative intent is common practice, its value is controversial. In the absence of conclusive clinical data, various modalities for the routine follow-up of patients with CRC have been proposed. In practice, the guidelines across countries and regions differ and are influenced by different health care policies, resource availability and doubts about effectiveness of follow-up. CONCLUSIONS: The results of metaanalyses of available clinical trials demonstrated a survival benefit of intensified monitoring, but the questions regarding the optimal frequency of visits and the examinations to be performed remain unanswered. Furthermore, intensive monitoring of CRC survivors may be difficult to be administrated, causes discomfort and morbidity to the patient and can have serious cost-implications to the healthcare system. However, as it seems from available data, a comprehensive surveillance program does not affect the quality of patients' life. Ongoing large prospective multi-institutional randomised trials might elucidate some of the crucial questions and existing dilemmas to establish adequate surveillance strategy for CRC patients.     

The influence of endocrine treatments for breast cancer on health-related quality of life

Many hormonal modalities are available for breast cancer treatment, such as selective oestrogen receptor modulators (SERMs), aromatase inhibitors, progestins and luteinising hormone-releasing hormone (LHRH) agonists. The long-term impact of these endocrine manipulations is an issue, because the duration of adjuvant treatment is still increasing, as is the number of breast cancer survivors. Premature menopause is induced at a young age, and may often be permanent after chemotherapy. The purpose of this review is to provide a literature-based overview of the side effects of endocrine treatment in pre- and postmenopausal breast cancer patients and the influence on HRQoL, especially on sexual functioning. The collection of health-related quality of life (HRQoL) data can result in better treatment recommendations during endocrine therapy. METHODS: This review was limited to prospective randomised studies in English literature from between 1977 and 2007 and provides an overview of the effects on HRQoL and sexuality of various hormonal treatment in pre- and postmenopausal breast cancer patients, both in the adjuvant and palliative setting. Relevant clinical studies were identified by using the Medline database. RESULTS: HRQoL mostly is severely influenced by chemotherapy and part of these symptoms may be lasting, especially when associated with the induction of premature menopause. Similar symptoms may be encountered during ovarian suppression therapy by LHRH analogs, but they will usually prove to be reversible. The varying side effect profiles of tamoxifen and aromatase inhibitors did not lead to significant difference in overall HRQoL. HRQoL during progestins and the SERM fulvestrant has been compared to this during aromatase inhibitors, and a large number of studies on HRQoL during endocrine therapy will be discussed.     

How American oncologists treat breast cancer: an assessment of the influence of clinical trials

The present study was designed to assess the preferred methods of treatment of breast cancer by American oncologists, and the impact of clinical trials on their practice. We mailed 465 questionnaires to surgical, radiation, or medical oncologists. The questionnaire described five hypothetic patients with breast cancer, and respondents were asked to select their preferred treatment for each patient. For primary breast cancer, most physicians would offer the choice of local excision followed by radiation therapy or modified radical mastectomy. About 80% of physicians would prescribe adjuvant chemotherapy for a premenopausal woman with estrogen receptor-negative, axillary node negative breast cancer, and for a postmenopausal woman with estrogen receptor-negative, node-positive disease. This policy was favored by male and female physicians of each specialty. Almost all respondents would treat a young woman with inflammatory breast cancer with initial chemotherapy followed by radiation and/or surgery, and about 60% would recommend chemotherapy to a postmenopausal patient with estrogen receptor-negative disease and minimally symptomatic bone metastases. Clinical trials have compared treatment strategies that could be applied to patients described in our questionnaire. Preferred treatments for primary breast cancer, and for inflammatory breast cancer are supported by the results of clinical trials. Recommendation of adjuvant chemotherapy for node-negative breast cancer is not based on a consistent demonstration of improvement in survival, although randomized trials with short follow-up have shown delay to recurrence. Recommendation of adjuvant chemotherapy for a postmenopausal woman with node-positive breast cancer is contrary to the results of large randomized controlled trials (and to a meta-analysis), which have shown that this policy does not lead to improved survival. Our report suggests that even large randomized clinical trials may have a minimal impact on practice if their results run counter to belief in the value of the treatment.