Abstract
Background:
Integrative Oncology (IO) interventions may decrease physical, psychological, and social distress related to cancer and its treatments. Little is known about the frequency and predictors of IO referral for symptom management for cancer rehabilitation inpatients.
Methods:
A retrospective review was performed of patients with cancer who underwent inpatient rehabilitation at a specialized tertiary cancer center from 5/2016 to 3/2020. Patient demographics and IO consultation details, including patient-reported outcome measures of symptom burden using ESAS-FS and functional status using the Activity Measure for Post-Acute Care “6 clicks,” were extracted. Descriptive summary statistics and logistic regression were used to analyze the data.
Results:
Out of 1196 inpatient rehabilitation admissions, 100 (8.4%) were referred to IO. The Activity Measure for Post-Acute Care “6 clicks” basic mobility admission scores were significant at a 1-point difference between the intervention and control group (39.5 vs 40.8, P < .05); both scores equate to a ˃50% degree of functional impairment. Referred patients were younger (62, P = .02) and Hispanics or Latinos (P = .02). The top symptoms for IO consultation included pain (N = 73), integrative approach (N = 41), relaxation (N = 38), and stress/anxiety (N = 33). Patients who reported a baseline symptom score ≥ 1 in the ESAS-FS, had both statistically (P < .05) and clinically significant improvements (≥1 point change) for pain, fatigue, well-being, anxiety, and sleep after massage therapy.
Conclusion:
Cancer rehabilitation inpatients were commonly referred to IO to address pain, with observed improvements across multiple symptoms with massage therapy. Lower mobility scores and younger patients received significantly higher referrals to IO. Larger trials are needed to characterize the effects of IO interventions on the inpatient rehabilitation of patients with cancer.
Keywords
Introduction
Patients with cancer have several needs that may not be completely met by standard cancer care.1 -4 These patients often experience physical, psychological, and social distress associated with the disease or its treatment.1 -6 To address their discomforts, patients with cancer are increasingly using complementary therapies to aid them during the course of their disease and treatment. 7 Music, acupuncture, yoga, meditation, and massage therapy are non-conventional therapies often used with patients with cancer. Music and yoga can improve mood, memory, stress, and anxiety. 8 Massage therapy can reduce anxiety, stress, pain, muscular tension, and fatigue. 7 Acupuncture has been shown to be effective in controlling postoperative pain and chemotherapy-induced nausea and vomiting.9,10
Numerous studies have been completed assessing the effects of music therapy, acupuncture, or massage therapy in cancer settings. A retrospective study revealed how inpatient music therapy can lead to significant improvements in global, physical, and psychosocial distress when recommended as part of an Integrative Oncology (IO) consultation. 11 A prospective study showed how cancer patients receiving inpatient acupuncture experienced significant improvements in pain, sleep disturbance, anxiety, drowsiness, nausea, and fatigue. 12 Outpatient massage therapy for patients with cancer studied retrospectively revealed major reductions in pain, fatigue, nausea, anxiety, and depression. 13 The Society for Integrative Oncology and American Society of Clinical Oncology both recommend music therapy for stress reduction and mood disorders, and they recommend massage for mood disorders. 14 However, changes in symptom distress before and after complementary therapy interventions has not been evaluated in the inpatient cancer rehabilitation (IPR) setting.
In a retrospective study by Fu et al 15 evaluating symptom and functional scores of 71 inpatient rehabilitation patients with cancer, both scores improved significantly during inpatient rehabilitation with 3 hours/weekday of a combination of physical therapy, occupational therapy, speech therapy, and/or group therapy. In a randomized controlled trial, 63 breast cancer patients underwent inpatient rehabilitation with 32 receiving a more structured physical training program compared to 31 receiving the standard rehabilitation program. 16 Instruments including the Functional Assessment of Chronic Illness Therapy Measurement System for Anemia/Fatigue, Hospital Anxiety and Depression Scale, and Multidimensional Fatigue Inventory were used to report symptoms. The authors found improvement from beginning to end of inpatient rehabilitation with global quality of life, physical well-being, and functionality in the trial group. 16 The studies by Fu et al 15 and Guo et al 17 looking at symptom distress in inpatient cancer rehabilitation have shown that the most distressing symptoms at admission were fatigue, poor sleep, poor appetite, well-being, and pain.15,17 While no significant correlation was noted between functional improvement and symptom distress, there was an improvement of fatigue, sleep, and pain with inpatient cancer rehabilitation. 15 Therefore, we assess the frequency and predictors of referral to IO and specific complementary therapies during inpatient cancer rehabilitation. We hypothesize that with the addition of music therapy, acupuncture, or massage therapy, symptom distress could improve even after 1 session.
Methods
A retrospective chart review was completed for patients with cancer undergoing acute IPR at a specialized tertiary cancer hospital with 760 beds, of which 13 to 16 beds are devoted to IPR, with access to inpatient integrative medicine consultations and interventions. One hundred consecutive IPR patients referred to IO were collected. We also gathered a list of all patients admitted to IPR from May 1, 2016 to March 23, 2020 not referred to IO. Controls were stratified by year of admission to match cases, and controls were randomly selected using a stratified random sampling method with Excel (Microsoft, Redmond, WA, USA). Sample size was derived from a two-sided 95% confidence interval. Figure 1 shows the diagram of patient flow. Patients may be referred by the Physical Medicine and Rehabilitation (PM&R) physician or advanced practice provider for IO consultation due to symptoms or to address patient questions about complementary medicine topics (eg, herbs and supplements). Our Integrative Medicine Program offers inpatient and outpatient consultation services. The inpatient consultation service uses an interdisciplinary team approach (physician and advanced practice provider consultation, yoga therapy, music therapy, massage therapy, and acupuncture) to address inpatient specific goals focused on symptom management. Beyond the initial integrative oncology physician consultation, our outpatient center includes additional resources (eg, exercise counseling, nutrition counseling, and health psychology) in support of a patient’s comprehensive integrative care plan. An IO physician and advanced practice provider jointly assess the patient as part of the initial integrative oncology consultation. Based on the comprehensive evaluation including patient history, examination and symptom assessment, patients are referred as appropriate to acupuncture, massage, and/or music therapy. Integrative interventions were each associated with an inpatient charge; no payment was collected at the time of treatment. This study was performed in line with the principles of the Declaration of Helsinki. The study was approved by the Institutional Review Board as protocol 2021-0539 noting the retrospective nature of the study, and all the therapies being performed were part of routine care.
Diagram of patient flow.
Inclusion criteria for IPR includes patients aged 12 and over of all cancer types and stages. Exclusion criteria were pediatric patients less than 50 kg due to nursing certifications on IPR. For acupuncture and massage, patients were excluded if they did not meet oncology massage or oncology acupuncture safety guidelines including absolute neutrophil count less than 1000, platelets less than 25 000, untreated deep venous thrombosis, or fever (temperature > 100.4) treatment. On IPR, patients are evaluated and treated Monday to Friday by an interdisciplinary team including a physiatrist, nurse, physical therapist, occupational therapist, speech-language pathologist, dietician, and case manager. Patients undergo 3 hours of intensive therapy a day for 5 days a week, with 1 hour of physical therapy, 1 hour of occupational therapy, and one additional hour of physical, occupational therapy or speech therapy depending on their needs. These therapies are performed in the patient’s room and gym on the floor. To address spiritual and psychosocial issues, a social worker and a chaplain are available on-site.
Music therapy, acupuncture and massage therapy interventions are delivered in patient rooms, either while in bed or at bedside. The integrative treatment plan is developed after comprehensive evaluation (eg, physical examination, history, patient reported outcomes assessments) by the integrative medicine physician and advanced practice provider in collaboration with the inpatient interdisciplinary integrative medicine team. The treatment plan for symptom management could include one or more different types of integrative therapies. Duration of the intervention was between 30 and 60 minutes, with all treatments done by licensed massage therapists, board certified acupuncturists, and a board-certified music therapist, all with over 5 years or more of experience in their respective specialties.
Physical and occupational therapy record patients’ functional status using Activity Measure for Post-Acute Care (AM-PAC) “6-clicks” as part of standard clinical care. This instrument was used to describe the difference in functional status between inpatient rehabilitation patients referred to IO compared to the matched controls who were not referred to IO. The AM-PAC instrument was created by researchers at Boston University, and each of the “6-clicks” instruments assesses different functional items. One assesses basic mobility such as walking, steps, and transfers; the other assesses daily activities such as dressing, bathing, eating, and toileting. 18 The AM-PAC “6-clicks” is a well-validated instrument with inter-rater reliability as measured by physical and occupational therapists.18,19 Using the information provided by the AM-PAC “6-clicks,” approximate degrees of functional impairment can be calculated which can be used to track the progress of intervention of physical and occupational therapies. 18
Patient-reported outcomes for patients referred to IO were collected using the Edmonton Symptom Assessment System - financial distress and spiritual pain (ESAS-FS), which is a modified version of the ESAS. A physician or advanced practice provider administers the ESAS-FS as part of the initial IO consultation. As part of the standard of care, the massage therapist, acupuncturist, and music therapist have the patient complete the ESAS-FS before and after each intervention. The ESAS-FS assesses 12 common symptoms experienced by patients with cancer over the past 24 hours. 20 The ESAS was developed in 1991 to assess symptom distress in the palliative care setting. 21 The ESAS is now widely used in clinical settings given its ease of use, and it has been validated for patients with advanced cancer. 22 In October 2012, the ESAS was modified to include 2 items following the same scale (0-10) to evaluate: Spiritual Pain and Financial Distress (ESAS-FS). The ESAS-FS includes symptoms of pain, fatigue, nausea, depression, anxiety, drowsiness, sleep, appetite, well-being, shortness of breath, spiritual pain, and financial distress.23 -25 We defined clinically significant change for a symptom as a change of ≥1 point on an individual symptom item score. 24
Statistical Analysis
Summary statistics like means, medians, standard deviations, and ranges were used for continuous variables, and frequencies and percentages for categorical variables. Characteristics were summarized separately for those referred to IO and those not referred to IO. The reasons for referral to IO (along with referral to each therapy) were summarized with frequencies and percentages. ESAS-FS scores were estimated and compared using a sign-rank test for pre- and post-intervention scores. For those with missing data, only pre-intervention scores were included in the analysis. The pre- and post-intervention data was compared once for each patient after their first session of massage, acupuncture, and music therapy. Due to small sample sizes, all analyses were not completed for acupuncture or music therapy. The admission AM-PAC “6-clicks” score was estimated along with a 95% confidence interval. All statistical analyses were performed using Stata/MP v17.0 (College Station, TX).
Results
There were 100 patients referred to IO out of 1196 inpatient rehabilitation admissions (8.4%) from May 2016 to March 2020. Out of the 100 patients, 13 did not receive any intervention due to thrombocytopenia, leukopenia, or non-availability of staff. Table 1 shows patient demographics for the 100 referred patients and for 100 controls. The referred group had a significant difference in age compared to controls (62 vs 66, P < .02), more Hispanic/Latino patients (P = .02), more cash pay, Veterans Administration or no insurance (P = .03), and more Christians (P = .00). There was no significant difference between the 2 groups in type of cancer or cancer status, race, or gender. The majority of referred patients had brain and other nervous system neoplasm type (37%) and advanced/metastatic cancer (67%). Admission scores using the AM-PAC “6 clicks” were collected to compare the referred to IO versus the control group. Basic mobility scores were significant at a 1-point difference between the referred and control group (39.5 vs 40.8, P < .05); both scores equate to a >50% degree of functional impairment. No significant difference was noted between the daily activities scores.
Demographics and clinical characteristics of patients referred to integrative oncology.
AM-PAC, activity measure for post-acute care.
Breast, Gastrointestinal, Gynecological, Head and Neck, and Lung.
Judaism, Buddhism, Islam, Sikhism, Hinduism, and not recorded.
Reasons for a consultation to IO are shown in Table 2 with pain (N = 73), integrative approach (N = 41), relaxation (N = 38), stress/anxiety (N = 33), fatigue (N = 27), and sleep disturbance (N = 23) being the most common. Recommendations included: massage therapy (81%) mostly for pain (94%) and fatigue (11%); acupuncture (53%) for pain (70%), fatigue (32%), nausea/vomiting (16%), sleep (11%), stress/anxiety (8%), and chemotherapy-induced peripheral neuropathy (6%); and music therapy (14%) for anxiety (57%), mood/depression (36%), rehabilitation support (29%), pain (21%), social interaction (14%), and other reasons such as fatigue and motivation (36%). Most patients referred to IO received at least 1 intervention: 81% were recommended massage therapy, of which 69 patients received at least 1 session, 10 did not, and 2 declined; 53% of patients were recommended acupuncture, of which 39 received at least 1 session, 10 did not, and 4 declined; 14% were recommended music therapy, with 11 patients having at least 1 session, 2 patients declined, and 1 did not complete. Five patients received both massage therapy and acupuncture, 1 patient received massage therapy and music therapy, and 1 patient received acupuncture and music therapy. Only massage therapy was counted as the intervention for analysis due to larger sample size.
Reasons for consultation with integrative oncology.
Total number of referral symptoms exceeds the number of patients as many patients had more than one reason for referral.
ESAS-FS scores were administered to patients referred to IO and subsequent to each intervention. Table 3 reports ESAS-FS scores at baseline and after treatment of the first session of massage therapy. The highest 3 mean ESAS-FS scores (SD) at the baseline assessment for massage therapy were pain 5 (3), sleep 5 (3), and fatigue 4 (3). Appendix Table 1 includes the highest 3 mean ESAS-FS scores (SD) at the baseline assessment for music therapy, which were pain 5 (3), fatigue 5 (4), and drowsiness 4 (3). Appendix Table 2 includes the highest 3 mean ESAS-FS scores (SD) at the baseline assessment for acupuncture, which were pain 4 (2), fatigue 4 (3), and sleep 4 (3).
Patient self-reported pre- and post-massage ESAS-FS scores.
Abbreviation: ESAS-FS, Edmonton symptom assessment system—financial distress and spiritual pain.
About 52 to 56 patients reported baseline ESAS scores (FS were only 14 patients), and 37 to 49 patients reported post-massage therapy treatment ESAS scores (FS were only 4 patients). The greatest improvements after the first session of massage therapy were in pain and fatigue with a 2-point improvement (P < .001), and well-being, sleep, and anxiety with a 1-point improvement (P < .001). These were both clinically significant (≥1 point mean change) and statistically significant (P < .05). Music therapy symptom scores were collected for 8 patients and only 2 patients completed the pre- and post-assessment, so statistical analysis was not performed due to the small sample size. Acupuncture had 34 patients who completed baseline assessment but only 9 patients completed the post-assessment, so statistical analysis was not performed due to the small sample size.
Discussion
This retrospective study is the first to our knowledge to look at IO referrals and integrative therapies on IPR for patients with cancer. We found that 8.4% of patients were referred to IO for consultation, and the most common reason for referral to IO was pain. Massage therapy was the most common intervention, and 1 session showed clinically significant improvement in ESAS scores for pain, fatigue, well-being, sleep, and anxiety. The National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology and Clinical Practice Guidelines on the Use of Integrative Therapies recommend massage to reduce cancer-related fatigue, pain, mood disturbance, and lymphedema.26,27 A systematic review from 2023 noted that massage can reduce cancer pain in patients with hematological malignancies, breast cancer, and cancers of the digestive system. 28 The review also recommended a massage duration of 10 to 30 minutes for the best effect, and the effect of a massage program length of ≥1 week in relieving cancer pain is better than that of <1 week. 28 The review suggested more studies are still needed on the degree of cancer, pain, cancer staging, and other aspects related to massage therapy in patients with cancer. 28 Furthermore, none of these studies took place with IPR patients with cancer. Ensuring effective management of patients’ symptoms is of significance during inpatient rehabilitation, as unmanaged symptoms can lead to decreased participation and adherence to the intensive rehabilitation program. 29
This study found that a low percentage (8.4%) of patients admitted to IPR were referred over 39 months. This may be due to ongoing medical problems preventing participation in certain interventions, such as massage and acupuncture due to pancytopenia. Thirteen percent of the 100 patients referred were unable to receive interventions due to these reasons. Patients with cancer undergoing IPR have been noted to have a high rate of medical complications, which may preclude complementary therapies while the focus is shifted to addressing urgent medical problems. 30 Limited rehabilitation physician experience with or knowledge about the potential benefits of IO and complementary therapies in the inpatient setting may have contributed to the observed low referral rate. We did not have inpatient yoga available during this period, so the lower referral rate for this therapy could also be due to a lack of availability.
Pain was the top reason for referral to IO consultation by the PM&R provider for 73 patients, and it was also the top reason for referral to massage therapy and acupuncture by the IO physician or advanced practice provider. The next most common reasons for referral to IO were the integrative approach (N = 41), relaxation (N = 38), stress/anxiety (N = 33), fatigue (N = 27), and sleep disturbance (N = 23). These results are consistent with prior studies, which supports the use of complementary therapies for pain management, especially for massage therapy.26,28 Our patient population was slightly different than prior studies, with a higher percentage of neurological cancer diagnoses and about 20% with hematological diagnoses. We were able to show that massage therapy can improve pain in the setting of inpatient rehabilitation, which reduces symptom burden for these patients with cancer.
Massage was also the most frequent complementary therapy used for our IPR patients. We hypothesize this may be due to a few reasons. The first is pain control, as on IPR, many post-surgical patients are admitted, for which massage is quite beneficial after surgery for myofascial pain. The second is the impact on fatigue, as many of the hematological patients report significant fatigue levels. 31 The third is the relaxation achieved with massage, as patients may be anxious about their cancer status and the next steps while undergoing rehabilitation to get stronger. Our study showed that massage significantly improves IPR patients with cancer fatigue, well-being, pain, anxiety, and sleep symptom burden scores within 1 session. It is possible that differences were not seen in pre- to post-intervention in other symptom distress scores because these were patients with lower symptom burden to begin with who would not be expecting to have significant improvement. This does not mean the treatment is not effective, but that this population did not have severe enough symptoms that are measurable.
We know from prior research that fatigue, poor sleep, poor appetite, well-being, and pain are significant symptoms on inpatient rehabilitation. 14 In our study, we showed that IPR patients exhibited moderate scores of distress in pain, fatigue, and sleep. They had symptom improvement with massage therapy in pain, fatigue, and sleep, as well as well-being and anxiety. The prior study by Fu et al 15 did not show symptom improvement with just IPR in patients with cancer, but another study by Riedl et al 32 did show improvement in fatigue, sleep, pain, HRQOL, anxiety, and depression with IPR. However, this patient population was quite different, with over 30% of patients with breast cancer compared to patients with neurological cancer in our study. More research is needed to see if the additive component of integrative medicine complementary therapies may be beneficial to this subset of patients.
The referral group had a greater mobility impairment at admission compared to the control group; both equate to a greater than 50% degree of functional impairment. However, there was no difference in daily activities scores when using the AMPAC “6-clicks.” We suspect that patients with a greater mobility impairment may be more willing to try integrative therapies to help achieve their goals. There was no significant difference in cancer type or status between the groups. We also found that the intervention group was younger, had more patients with religion reported as Christianity, had more patients without insurance, Veterans administration insurance or self-pay, and consisted of more Hispanic/Latino patients. The percentage differences in religion, insurance, and ethnicity were, however, quite low. More research with a larger sample size is needed to better characterize the distribution of referrals to IO and to better understand which IPR patients are referred to IO.
Music therapy and acupuncture had very few responses post-treatment documented. We were unable to make observations regarding pre/post symptom change for these 2 interventions due to the low post-treatment response rate. These patients did have initially low to moderate ESAS scores for pain, fatigue, anxiety, drowsiness, poor appetite, well-being, and sleep, which are slightly lower than prior studies for acupuncture and music therapy in hospitalized patients with cancer.11,12,33 More research is needed with a higher power study to see if the symptom distress is overall lower in patients with cancer undergoing IPR compared to other hospitalized patients with cancer.
Limitations of the study include that it is an analysis of observational data without the ability to control for other interventions that may have contributed to symptom improvement during that day. For patients with missing ESAF-FS data, only pre-intervention scores were described. One major limitation is that the post-treatment ESAS was only obtained for a small percentage of patients in acupuncture and music therapy. Prior literature has shown in acupuncture patients that there was no systematic difference in those that completed ESAS post-treatment, and the major reason for it not being completed was due to the patient being asleep from relaxation. 12 Having the ESAS administered by the therapists also introduces a potential for bias, as the patient may report improvement from a desire to please the therapist. Our results were limited to the immediate effects of a single therapy session, which does not allow us to measure the durability of these effects throughout IPR. We also acknowledge the generalizability of this study may be limited by a referral bias as we are a large, specialized tertiary cancer center, but this may serve as a reason for other inpatient cancer rehabilitation facilities to work toward access to IO and these therapies.
Conclusion
This retrospective study describes the effects of IO complementary therapies on inpatient cancer rehabilitation patients. We found only a small percentage of IPR patients were referred for IO therapies during the 13-month period, of which patients were younger and with a greater mobility impairment. As we work toward more non-pharmacologic strategies to help with symptom management on IPR, we should work toward identifying which therapies can provide clinically meaningful benefits. Our real-world analysis shows that massage therapy improves pain, fatigue, well-being, anxiety, and sleep for IPR patients with cancer. Larger trials are needed to identify patients who will benefit, characterize the effects of other IO therapies on IPR in patients with cancer, as well as explore the longitudinal effects of massage therapy. Future research with a randomized controlled trial to explore the improvement in symptom distress from IPR in addition to complementary therapies and their impact on functional change is needed.
Footnotes
Appendix
Patient self-reported pre- and post-acupuncture ESAS-FS scores.
| Symptom | Pre (N) | Post (N) | Mean change (SD) | P-value |
|---|---|---|---|---|
| Pain | 4 (34) | 2 (9) | −2 (2) | .13 |
| Fatigue | 4 (32) | 2 (8) | −1 (2) | .13 |
| Nausea | 1 (33) | 1 (8) | 0 (1) | >.99 |
| Depression | 2 (32) | 1 (8) | 0 (1) | >.99 |
| Anxiety | 3 (32) | 1 (8) | 0 (2) | .88 |
| Drowsiness | 3 (31) | 2 (9) | 0 (1) | .93 |
| Sleep | 4 (30) | 3 (8) | 0 (3) | .63 |
| Appetite | 3 (31) | 2 (9) | 0 (1) | .32 |
| Well-being | 3 (30) | 1 (8) | −2 (2) | .06 |
| Shortness of breath | 2 (32) | 1 (8) | −1 (3) | .23 |
| Spiritual Pain | 3 (4) | 0 (0) | 0 (0) | >.99 |
| Financial Distress | 2 (6) | 0 (1) | 0 (0) | >.99 |
Abbreviation: ESAS-FS, Edmonton symptom assessment system—financial distress and spiritual pain.
Acknowledgements
Andrew Cusimano for assistance with data collection.
Authors’ contributions
Ekta Gupta, Gabriel Lopez, Santhosshi Narayanan, Jegy M. Tennison, Bryan M. Fellman, and Eduardo Bruera contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Ekta Gupta, Aline Rozman de Moraes, Imran Elahi, and Bryan M. Fellman. The first draft of the manuscript was written by Ekta Gupta, Gabriel Lopez, Santhosshi Narayanan, Jegy M. Tennison, Bryan M. Fellman, and Eduardo Bruera, and all authors commented on previous versions of the manuscript. Ekta Gupta and Gabriel Lopez are co-first authors as they have contributed equally to the manuscript. All authors read and approved the final manuscript.
Data Availability
The data sets generated and/or analyzed during the current study are stored at UT MD Anderson Cancer Center. They are available from the corresponding author upon request.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Statistical staff was partly supported by the National Institutes of Health through M.D. Anderson’s Cancer Center Support Grant CA016672.
Ethical Approval
This study was performed in line with the principles of the Declaration of Helsinki. The study was approved by the IRB of the University of Texas MD Anderson Cancer Center given the retrospective nature of the study and all the procedures being performed were part of routine care (PA2021-0539).
Code Availability
Not applicable.
Consent to Participate
The need for written informed consent was waived with the Institutional Review Board’s guidance.
Consent for Publication
Not applicable. All data were de-identified.
