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REVIEW ARTICLE
Year : 2023 | Volume
: 9
| Issue : 3 | Page : 235-242
Symptom assessment and management in patients with lung cancer undergoing conventional or traditional chinese medicine care
Bao-Jin Han1, Ya-Jie Liu2, Jia-Yue Jin1, Hong-Kun Xu3, Wen-Zheng Zhang3, Si-Meng Ren3, Xin Shelley Wang4, Jie Liu3
1 Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences; Graduate School, Beijing University of Chinese Medicine, Beijing, China
2 Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
3 Graduate School, Beijing University of Chinese Medicine, Beijing, China
4 Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Correspondence Address:
Prof. Jie Liu
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange Street, Xicheng, Beijing 100 053
China
Prof. Xin Shelley Wang
Department of Symptom Research, Unit 1450, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston 77030, TX
USA
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/2311-8571.382112
Patients with lung cancer may experience various symptoms as the disease progresses, which may reduce the benefits of cancer treatment, reduce treatment compliance, delay cancer treatment, reduce the quality of life (QoL), and impact survival. This review discusses comprehensive symptom assessment and management, which are crucial for high-quality lung cancer treatment. Traditional Chinese medicine (TCM) is important in relieving cancer-related symptoms in patients with lung cancer. Including patient-reported outcomes (PROs) in clinical trials and practice can provide a better assessment of symptom burden and the effectiveness of symptom management. Patient-centered care with TCM in lung cancer patients may include six steps: Symptom screening, etiology investigation, comprehensive assessment, integrative management, reassessment, and regular symptom follow-up monitoring. PRO measures can be used to evaluate symptom intensity, the degree to which symptoms interfere with activities of daily living, and the QoL. Clearly defined and reliable PRO measures can enhance patient satisfaction and improve symptom control. Quantitative PRO measures developed from the TCM perspective should be considered one of the important outcome measurements in TCM care. A multidisciplinary collaborative symptom management model, including TCM and conventional therapy, will be the future goal for treating patients with lung cancer.
Keywords: Lung cancer, symptom assessment, symptom burden, symptom management, traditional Chinese medicine
An estimated 2.2 million new lung cancer cases occurred worldwide in 2020; it was the second most commonly diagnosed cancer, representing 11.4% of all diagnosed cancers.[1] In China, lung cancer is the most common cancer and the leading cause of cancer deaths.[2] As lung cancer progresses, patients may experience multiple symptoms, greater symptom burden than in other cancers, and greater symptom distress.[3],[4] Bubis et al. found that fatigue, anxiety, depression, poor appetite, and pain were the most common moderate-to-severe symptoms in patients with cancer in general, and patients with oropharyngeal or respiratory cancer had a higher symptom burden than those with other cancers.[5]
The most common symptoms among patients with advanced lung cancer were fatigue (100%), loss of appetite (97%), shortness of breath (95%), cough (93%), pain (92%), and bloody sputum (63%).[6] A comprehensive study demonstrated that 13 symptoms co-occurred within a month after lung cancer surgery, four of which were experienced by over 80% of patients: Shortness of breath (86%), lack of energy (84%), pain (84%), and drowsiness (83%).[7] A cross-sectional survey reported that the top three most prevalent symptoms among patients undergoing chemotherapy for lung cancer were fatigue (100%), distress (99%), and lack of appetite (97%); the top three moderate-to-severe symptoms were fatigue (6.24 ± 1.70), dry mouth (4.86 ± 2.11), and shortness of breath (4.88 ± 2.52).[8] Lung cancer survivors often live with long-term disease, and the residual side effects of treatment, fatigue, dyspnea, and cough, persist for up to 5 years during survivorship.[9]
The presence of comorbidities, pulmonary complications, and poor functional status (rated a low Eastern Cooperative Oncology Group performance score) were all associated with a high risk of lung cancer symptoms interfering with activities of daily living.[10] Emotional distress is more commonly experienced by patients who have undergone surgery or chemotherapy and current cigarette smokers.[11] Patients who are younger, unmarried, female, non-Hispanic white, less educated, unemployed, or with low socioeconomic status may experience more severe symptom burden, emotional distress, and poorer quality of life (QoL).[8],[11],[12],[13],[14],[15] Low socioeconomic status is associated with a lack of access to proper healthcare, inadequate social support, and increased financial distress.[16] Moreover, a lack of family or social support may result in a higher psychological symptom burden and interference with the activities of daily living.[17]
A high symptom burden may reduce cancer treatment benefits, delay treatment, reduce treatment compliance, reduce patient QoL, and impact survival. Appropriate identification, measurement, and management of symptoms can improve patients' physical and psychosocial well-being and might reduce their financial burden.[18] More efficient symptom management using traditional Chinese medicine (TCM) or other approaches is associated with better QoL and greater treatment compliance and may even be associated with survival benefits.
In this review, we discuss a comprehensive approach to symptom assessment and management of patients with lung cancer to provide a perspective on high-quality patient care for lung cancer.
Benefits of Symptom AssessmentProviding high-quality symptom assessment is vital for delivering holistic, patient-centered care that yields positive outcomes for patients and their families. Compared with usual care, implementing patient-reported outcome (PRO)-based symptom management after lung cancer surgery is linked to reduced symptom burden and fewer complications for up to 4 weeks following discharge.[19] Moreover, the dynamic assessment of symptoms can provide early signs of complications. An observational study found that patient-reported radiation pneumonitis-related symptoms are early signs of a higher risk of radiation pneumonitis.[20] Scientific symptom assessment can improve patients' long-term survival outcomes. Basch et al. found that electronic patient-reported symptom monitoring prolonged the median overall survival duration to 31.2 months compared with 26.0 months in usual care.[21]
Patient-report Outcome MeasuresAccurate assessment of patients' symptom burden, health-related QoL (HRQoL), and treatment response is critical for improving patient outcomes, providing high-quality cancer treatment, and performing clinical research. To guide the industry in including PROs in medical product development, the US Food and Drug Administration defined PROs in 2009 as “any report of the status of a patient's health condition that comes directly from the patient, without interpretation of the patient's response by a clinician or anyone else.”[22] Well-defined and reliable PRO measures can scientifically assess symptom burden in patients with lung cancer [Table 1].
Single-item patient-reported outcome measures
These are single-item PRO measures useful for determining ambulatory care patients' current status and detecting commonly encountered symptoms in patients with lung cancer, such as pain, fatigue, dyspnea, and cough. A single-item PRO measure can help clinicians efficiently detect the target symptoms.[23] Widely known single-item PRO measures include the Visual Analog Scale, 11-Point Pain Intensity Numerical Rating Scale (PI-NRS), Verbal Rating Scale, and Wong-Baker FACES Pain Rating Scale.[24],[25],[26],[27] One study found that most patients preferred specific scales; the Categorical Response Scale was preferred for appetite loss and fatigue, while the 11-Point PI-NRS was preferred for pain.[28]
Multi-item patient-reported outcome measures
A multi-item PRO measure is useful for assessing the current status of patients in clinical trials. Multi-item PRO measures are designed to capture multiple symptoms or the characteristics of a single symptom (e.g., frequency, severity, duration, timing, and impact on physical functioning status).
Throughout the disease course, patients with lung cancer may simultaneously experience a collection of symptoms.[29] The concept of a “symptom cluster” was proposed by Dodd et al. in 2001, with three or more related symptoms occurring concurrently.[30] Since then, increasing attention in symptom research has been directed toward evaluating symptom clusters rather than isolated symptoms, especially among patients with lung cancer.[31],[32],[33] Some of the most commonly used validated and reliable scales for assessing symptom clusters are the Edmonton Symptom Assessment Scale (ESAS), MD Anderson Symptom Inventory (MDASI), and Memorial Symptom Assessment-Short Form (MSA-SF).[34],[35],[36] Compared with single-item PRO measures, multi-item symptom PRO measures may be more comprehensive and better able to elucidate the state of symptom burden.
In clinical trials, multiple characteristics of a single symptom measure can be used to assess target symptoms in specific patient populations. For example, the Brief Pain Inventory (BPI) and Brief Fatigue Inventory (BFI) are commonly used to assess the severity of pain and fatigue and the degree to which they interfere with daily activities. The BPI assesses and categorizes pain as worst, least, average, and right now. The seven aspects that interfere with daily life are general activity, mood, walking, normal work, relations with other people, sleep, and enjoyment of life.[37] Using multiple characteristics of a single symptom measure may minimize bias in the PROs of symptom burden and assist clinicians in obtaining complete symptom information. A metric can be assigned to a target symptom to monitor the effectiveness of symptom management.
Multidimensional patient-reported outcome measures
A multidimensional PRO measure depends on the goal and assesses patients' symptom burden, health status, or HRQoL. The most commonly used multidimensional QoL PRO measure is the European Organization for Research and Treatment of Cancer quality of life questionnaire 30-item core measure (EORTC QLQ-C30), which covers basic QoL domains, including physical, emotional, and social functioning, and global QoL.[38],[39] To address the symptoms associated with lung cancer and its treatment, researchers developed a supplementary lung cancer-specific questionnaire module and administered it alongside a core questionnaire.[40] The Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) and the Functional Assessment of Cancer Therapy Scale-General (FACT-G) are widely used QoL PRO measures in clinical trials.[41],[42],[43]
Selection of Patient-reported Outcome MeasuresA meticulous selection of the most appropriate PRO measures is essential for successfully implementing a clinical trial or providing patient care. An appropriate PRO measure for dynamic symptom assessment will help clinicians respond to patient concerns and issues and intervene at the best time.[44]
Researchers should perform the following steps in clinical trials of symptom management, either as a primary or secondary outcome.[45],[46] (1) Identify the study population, intervention, context, objectives, and setting. (2) Determine the validity, reliability, and sensitivity of the PRO measures in the target patient population and an appropriate recall period. (3) Create a rigorous statistical analysis plan to calculate the sample size, expected PRO changes, and pitfall data. (4) Develop a detailed plan for collecting PRO data, ideally via an electronic PRO. (5) Train the research staff and provide patients with clear instructions before collecting data. A balance must be established between comprehensive data collection and patient compliance with assessments. Efficient rating of symptoms and other symptom-related health domains should prioritize minimizing patient time expenditure (ideally within 20 min at baseline and 10–15 min at subsequent time points).
In patients with advanced disease or those in the active treatment period, symptom changes may occur more rapidly, and more frequent assessments are needed. In this instance, a shorter PRO measure, such as the MDASI-lung cancer, ESAS, MSA-SF, BPI, BFI, and Lung Cancer Symptom Scale, can minimize patient and staff burden while capturing symptom burden and other QoL dimensions.[47] Core symptom burden and HRQoL can be assessed in patients years after surgery or after they are cancer-free in long-term survivorship using the EORTC QLQ-C30 measure and Medical Outcomes Study SF-36.[48],[49],[50] For patients with lung cancer, having to rate too many domains frequently could be overwhelming. However, it could also be boring for survivors with little symptom distress who require symptom monitoring.
TCM has been used in clinical practice for many years to extend survival and relieve symptom burden in patients with lung cancer.[51],[52] TCM often targets a cluster of symptoms (e.g., fatigue, insomnia, or anxiety). To effectively assess the specific effect of TCM on symptom clusters in the oncology population, PRO measures must be developed from a TCM perspective.[53] Various psychometrically validated PRO measures have been recommended. For example, the TCM Spleen Deficiency Syndrome (TCM-SDS) Scale evaluates SDS in patients with colorectal cancer,[54] and the TCM Health Self-Evaluation Scale (TCM-50) assesses the health status of patients from a TCM perspective.[55] The Body Constitution Questionnaire was developed to categorize individuals into different body constitution types based on TCM theories.[56] The MDASI-TCM module measures the severity of multiple symptoms and their interference with functioning in patients with cancer receiving TCM-based care.[57]
Development of Patient-reported Outcome MeasuresA new PRO measure must be developed if no previously psychometrically validated PRO measure is available or if the existing measure has certain limiting factors for assessing specific PROs in a cohort of patients. The development of the measure should follow the necessary process and be psychometrically validated for feasibility, reliability, validity, and sensitivity to change before it is formally applied in clinical practice and trials.[22],[58]
The efficacy of TCM should be evaluated using PRO measures developed from a TCM perspective. Researchers have made great efforts to explore the development modes of TCM PRO measures, as there is still no consensus about the TCM PRO measure development framework. Guo et al. developed a Syndrome Evaluation Scale of Liver Depression and Heat Syndrome that evaluates the main symptoms within a specific syndrome framework.[59] Wang et al. developed a PRO scale for stroke, which performs comprehensive multidimensional evaluations from the perspective of TCM.[60],[61],[62] Guo et al. developed a Syndrome Diagnosis Scale for Liver Depression Transforming into Heat Syndrome that determines the diagnosis based on TCM syndrome differentiation.[63] However, previous TCM PRO measures have some limitations. For example, some TCM PRO measures lacked terminology standardization; some mixed up the diagnosis and efficacy measures, and some set barriers for clinicians without a TCM background. TCM has the advantage of multi-symptom management; therefore, evaluating TCM efficacy by measuring symptom clusters is important. Evidence-based and clinically meaningful screening with a psychometrically validated PRO measure can be used to evaluate TCM's specific impact on symptom clusters.
Symptom ManagementOptimal symptom management in patients with lung cancer includes six steps: Screening, etiology investigation, comprehensive assessment, integrative management, reassessment, and regular follow-up [Figure 1].
Symptom screening and etiology investigation
Clinicians should perform routine symptom screening at every visit, and a single-item screening measure per symptom can be used for screening. Clinicians should investigate the symptom etiology if patients report a moderate to severe symptom burden. Symptoms may be due to cancer itself, cancer treatment, or comorbidities.
Comprehensive symptom assessment
Comprehensive symptom assessment should be used and should mainly include a review of three key elements: (1) medical history, (2) symptom history, and (3) social and family support. Medical history reviews should include information on disease status, cancer treatments, disease recurrence and progression, comorbidities or cancer treatment sequelae, and nutritional status. A thorough medical examination, body system review, and laboratory tests can help clinicians accurately identify the causes of symptoms. A symptom history review should include symptom onset, duration, severity, and changes over time; how symptoms interfere with physical function and mood; and associated or alleviating factors. PRO measures can be used to assess symptom severity, the degree to which symptoms interfere with function and mood, unrecognized concomitant symptoms, and HRQoL. In addition, clinicians should consider patients' social and family support status, caregiver availability, economic status, mental health status, and symptom management preferences.[64] Clinicians should offer individual interventions only after all elements have been assessed.
Integrative management
Integrative management includes etiological and symptomatic treatments and should be considered once any underlying or reversible causes of symptoms have been treated. Many professional societies have published symptom management guidelines.[65],[66],[67] In addition to conventional therapies for cancer-related symptoms, the National Comprehensive Cancer Network Practice Guidelines recommend complementary and alternative medicines to relieve symptoms.[68],[69] Well-designed research on symptom burden or benefit through PROs from TCM symptom management would provide evidence-based, high-quality symptom management.
Patients with lung cancer may encounter symptom clusters throughout their disease course.[70] Thus, a group of symptom clusters may share common underlying mechanisms and outcomes.[71],[72] Treatments for one symptom may “crossover” and reduce the severity of other symptoms included in the cluster.[73] To improve patients' well-being, we should focus on developing strategies for managing symptom clusters. It is also necessary to be aware of the possibility of other accompanying symptoms and patients' psychological states.[17],[74]
Reassessment and follow-up
Symptoms should be conducted to determine treatment efficacy. If a patient reports persistent symptom burden, symptoms should be screened and evaluated at every clinical or online visit.
Efficacy of Symptom ManagementIn clinical practice and trials, it is crucial to establish the minimal clinically important improvement (MCII)/minimal clinically important difference (MCID) for PRO changes. The MCII was established to determine the smallest change that patients perceived as beneficial.[75] In patients with lung cancer, anchor- and distribution-based methods are the most widely used means of identifying MCII.[75],[76],[77] An MCII score of 30% was recommended for a reduction in pain intensity from baseline with an 11-Point PI-NRS in a chronic pain clinical trial.[78] Researchers determined that for each of the ten symptoms assessed using the ESAS, an optimal cutoff of 1 point indicated improvement, while -1 point indicated deterioration.[79] A mean of 1.71–2.16 points is necessary to perceive an improvement in symptom intensity.[80] In total, 30% of patients with MCII showed meaningful recovery after video-assisted thoracoscopic surgery for MDASI-lung cancer.[81]
Patients with lung cancer may experience different symptoms at different stages of the disease. The introduction of symptom threshold events (STEs) is conducive to the scientific and accurate evaluation of the advantages and characteristics of TCM in managing symptoms and easing filling burdens. Thresholds were set for symptom severity scores, and the number of events that reached STE was counted.[82] STEs were first used in a clinical symptom intervention evaluation study. They included all symptoms of ≥4 points after lung cancer surgery.[83] Setting the STE of the target population can help researchers quickly identify and manage target symptoms.
In clinical practice, Hui et al. reported that the personalized symptom goal is ≤3 (11-point NRS) for most patients.[84] Acceptable symptom severity among patients with advanced lung cancer was ≤3.1.[85]
DiscussionPatients with lung cancer may experience multiple symptoms throughout their disease course. Dynamic symptom monitoring and comprehensive symptom assessment can help trace symptom changes and guide optimal intervention time, thereby serving as an early warning signal for serious complications and providing prompt and early intervention. Well-validated PRO measures are useful for assessing the symptom burden in patients. Researchers and clinicians should select appropriate PRO measures for their population, interventions, contexts, objectives, and settings. If no appropriate PRO measures exist, they should be developed following a standardized development process. TCM often targets multiple symptoms, known as symptom clusters,[53],[86] and PRO measures developed from a TCM perspective can be used to evaluate the effectiveness of TCM and promote its evidence-based approach.
In conventional oncological treatments (including chemotherapy, radiotherapy, immunotherapy, and surgery) and TCM care, symptom management relies on high-level empirical evidence to support the development of formal guidelines.[87] Therefore, time and toxicity or complication-sensitive fit-for-purpose PROs for lung cancer assessment are urgently required.
In TCM practice, symptom management is based on “Zheng” (core symptoms by phenotypes according to TCM theory), with pulse feelings and tongue appearance collected and analyzed by TCM clinicians to identify TCM syndromes. The clinician also considers the patient's current natural and social environment and psychological status before providing individual symptom management, a process known as syndrome differentiation. TCM includes multiple targets to address symptom clusters. Patient responses to symptom management and functioning status can be objectively recorded using PROs.[88]
Conventional medical symptom management is precise, whereas TCM is holistic. High-quality, evidence-based symptom management should take advantage of both conventional and TCM therapy. Multidisciplinary collaborations should be used to promote fit-for-purpose integrative medicine measurements for patients with lung cancer and provide high-quality, evidence-based medicine to manage symptom clusters. This will open the door to effective treatment of these patients.
Acknowledgments
The authors also gratefully acknowledge Ann Sutton from the MD Anderson Cancer Center for providing English editing services during manuscript preparation.
Financial support and sponsorship
This study was financially supported by the Capital Clinical Characteristic Application Research Project of the Beijing Science and Technology Commission (No. Z181100001718175) and the Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences (No. CI2021A05502).
Conflicts of interest
There are no conflicts of interest.
References
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