A Retrospective Cohort Study on the Preliminary Efficacy of Massage Therapy for Chemotherapy-Induced Peripheral Neuropathy Among Cancer Patients

Abstract

Purpose:

Chemotherapy-induced peripheral neuropathy (CIPN) worsens the quality of life for people with cancer. Massage therapy involves neuromuscular modulations and can potentially reduce CIPN symptoms. We examined the immediate improvements in CIPN-related pain and neuropathy following massage therapy among patients with CIPN.

Methods:

In a retrospective cohort, we assessed patients who received 1 massage therapy session for CIPN symptom relief during or after chemotherapy at a National Cancer Institute-Designated Comprehensive Cancer Center from October 2017 to September 2022. We measured the severity of pain and neuropathy before and after massage therapy with a 4-item verbal rating scale (VRS) or a 0 to 10 numerical rating scale (NRS). We converted NRS to VRS scores and examined the pre-post differences in symptom severity using the Wilcoxon rank test.

Results:

Among 23 patients (median [range] age 64 [4-85] years, female 74%, White 70%), one session of massage therapy decreased the percentage of patients reporting moderate-to-severe pain from 81% at baseline to 0% (none) post-massage; percentage of patients reporting neuropathy also reduced from 77% at baseline to 12% following treatment. The pre-post differences were statistically significant for both pain (mean: −1.6, 95% confidence interval [CI] −1.9 to −1.2; P = .001) and neuropathy scores (mean: −1.2, 95%CI −1.4 to −0.9; P < .0001).

Conclusion:

Among cancer patients with CIPN, one session of massage therapy was associated with immediate neuropathy and CIPN pain relief reported by patients following treatment. However, this preliminary finding requires further rigorous verifications in future randomized controlled clinical trials.

Introduction

Up to 63% of patients with cancer receiving neurotoxic chemotherapy develop chemotherapy-induced peripheral neuropathy (CIPN),^1-3 experiencing numbness, tingling, and pain in the limbs.^4-6 CIPN may cause functional impairments and deteriorate patients’ quality of life, ⁷ leading to chemotherapy dose reduction or early discontinuation and raising concerns about cancer treatment efficacy and mortality. ³ Duloxetine is thus far the only medication the American Society of Clinical Oncology (ASCO) recommends for CIPN pain management. However, it remains limited in treatment response and can induce undesirable side effects such as fatigue, insomnia, and nausea.^8-10 Given patients’ concerns about polypharmacy, ¹¹ there is a pressing need for nonpharmacologic approaches to address CIPN symptoms among patients with cancer.

Massage therapy involves manual manipulation of muscles and other soft tissues by therapists and has been recommended in clinical practice guidelines to alleviate pain in non-cancer populations. ¹² It offers varied mechanosensory stimulations by styles, that is, Swedish massage, Chinese Tuina, reflexology, and neuromuscular therapy, to release tension, improve lymphatic and blood circulation, and promote relaxation.^13-15 Basic science studies reveal that massage reduces inflammation and promotes mitochondrial biogenesis to alleviate pain and facilitate skeletal muscle rehabilitation. ¹⁶ In the oncological setting, massage therapy is recommended for depression/mood disorder management ¹⁷ and is promising for reducing CIPN pain, according to pilot studies.^18-21 However, current trials are limited due to the lack of valid sham controls, objective outcome measures, and intervention standardization. Whether short- or long-term massage therapy results in pain and neuropathy relief among patients with CIPN remains unclear.

While the exact mechanism by which massage therapy mitigates CIPN symptoms is currently under investigation, massage improves circulation, reduces stress, and promotes metabolism. ¹³ Applying compression throughout the body or to the affected feet or hands with massage stimulates nerve fibers, suppresses pain perception, balances metabolism, and activates neuroimmunological mechanisms. ²² As CIPN involves axon blockage and subsequent axonal degeneration and damage to dorsal root ganglia sensory neurons, ²³ massage may also alleviate CIPN by reducing levels of neutrophils and proinflammatory cytokines to ameliorate inflammation and promote mitochondrial biogenesis.^16,24 Further studies are still needed to explore the mechanism of massage in reducing CIPN symptoms.

Retrospective chart reviews allow clinicians and researchers to closely examine patients’ symptom experiences and permit preliminary efficacy signal investigation in the early intervention development phase. ²⁵ To explore the preliminary efficacy of massage therapy on improving CIPN symptoms and further inform the design of a prospective trial, we collected patient-reported pain and neuropathy outcome data, retrospectively, from the integrative medicine clinic at Memorial Sloan-Kettering Cancer Center (MSKCC), and evaluated the pre-post changes in the severity of CIPN-related pain and neuropathy among patients with CIPN following one session of massage therapy administered during the chemotherapy regimen or after the completion of an entire chemotherapy course.

Material and Methods

Setting and Participants

Among 255 total patients who received one session of massage therapy at MSKCC from October 2017 to September 2022, 23 patients met the following inclusion criteria: (1) massage therapy during the course of chemotherapy treatment or after completion of the scheduled chemotherapy regimen (defined as the course of the treatment over a period of time). Once a clinical diagnosis of CIPN was confirmed by a patient’s oncologist or primary care physician, massage therapy would be provided either in concurrence with the active chemotherapy treatment (prior to a consecutive chemotherapy session after CIPN development) or after completion of the scheduled chemotherapy regimen. (2) Explicit CIPN symptoms in the electronic medical record (EMR) addressed by the massage therapist. Massage therapy varies in practice to address different symptoms, such as pain, mental distress, sleep, or fatigue. In this study, we only included patients who received massage therapy and explicitly requested that their CIPN symptoms, that is, pain, numbness, and tingling, be addressed. The presence of CIPN was documented in the patient’s EMR by their oncologist or primary physician (Figure 1).

Figure 1.

Study flow chart.

Abbreviations: VRS, verbal rating scale; NRS, numerical rating scale.

IRB Approval and Informed Consent

MSKCC IRB reviewed and approved the study protocol (IRB-17-481) in accordance with the Declaration of Helsinki. This retrospective chart review study did not involve prospective data collection, presented minimal risks to patients, and was exempted from informed consent by the MSKCC IRB.

Intervention/Exposure

Licensed massage therapists with at least 5 years of clinical experience working with oncological patient populations provided massage therapy. The oncology massage therapist has fixed massage therapy manuals with different massage approaches/techniques to address CIPN symptoms, where pain is a primary symptom to tackle. Patients included in this analysis were those who sought massage therapy to address their concerns about CIPN symptoms. This study tried to minimize the confounding of other non-CIPN-related pain and captured the possible effect of massage on CIPN-related pain and other symptoms at its maximum capacity, as the massage therapist instructed patients to report the severity of symptoms specific to CIPN.

Each massage therapy session lasted between 20 and 60 minutes and had varied forms, that is, Swedish massage, reflexology, or neuromuscular therapy, and targeted the whole body or specific body parts. Swedish massage is the classic European massage, which aims to facilitate circulation, reduce excess muscle tension, increase flexibility, and promote relaxation. ²⁶ Reflexology is a type of massage that stimulates points on the feet, hands, and ears, mirroring organs and tissues of the human body to achieve therapeutic effects. ¹⁵ Neuromuscular therapy applies pressure and strokes, most commonly by finger or thumb contact, to remove local and reflexogenic sources of pain and dysfunction. ²⁷ The intervention was tailored by massage therapists in communication with patients to address their needs and preferences adequately.

Pain and Neuropathy Outcome Measurement

The severity of CIPN-related pain and neuropathy was measured pre-and post-treatment with an 11-point numerical rating scale (NRS) and a 4-category verbal rating scale (VRS). Both NRS and VRS are validated and widely used in pain symptom research and care; in this study, patients decided to use either one or both outcome measures offered by the massage therapist. The 0 to 10 NRS is a numeric scale, with 0 representing no symptoms and 10 representing the worst symptoms imaginable. It has been widely used to measure the severity of symptoms, especially pain, with high reliability and validity.^28-31 The NRS is a valid and reliable instrument to measure the intensity of CIPN symptoms (pain, tingling, numbness).^32,33 The 4-category VRS measures symptoms, particularly pain, in 4 incremental levels using the adjectives: “none,” “mild,” “moderate,” and “severe.” ³⁴ It has been validated in measuring pain severity in post-surgical and advanced cancer patients and has demonstrated good validity and reliability.^35-39 The massage therapist used the VRS and NRS in clinical practice to understand patients’ symptom changes following the intervention; their results were recorded in the EMR.

Patient-Reported Treatment Satisfaction

At the end of the session, the massage therapist interviewed patients to summarize their treatment satisfaction. Any feedback, including positive and negative comments about the therapeutic process, was recorded as a medical note in the EMR.

Data Source, Extraction, and Management

All data, including demographics and clinical characteristics, intervention, pain and neuropathy outcomes, and treatment satisfaction, were sourced from EMRs at the Integrative Medicine clinic at MSKCC. Two independent researchers extracted patient data by reviewing EMRs following a data extraction form. Clinical researchers determined study participants’ eligibility under a medical oncologist’s oversight. Two independent researchers controlled data quality by comparing the extracted data with the original EMR data. Any discrepancy in data was resolved by confirming with the massage therapists, research coordinators, and oncologists.

Statistical Analysis

We summarized patient demographics and clinical characteristics with descriptive statistics. Continuous variables (age) were summarized with means and standard deviations. Categorical variables (sex/gender, race, chemotherapy status, number of massage types received during session, massage style, and cancer type) were summarized with percentages or percentiles.

For the clinical outcomes, we hypothesized that among patients with CIPN, massage therapy reduced the pain and neuropathy severity measured with the VRS or NRS, with significant differences in pre- versus post-treatment symptom severity scores. We summarized the VRS pain and neuropathy severity scores with percentages. We had planned to compare the pre- versus post-treatment NRS pain and neuropathy severity scores with paired t-tests. However, among 23 patients who reported either pain or neuropathy with VRS or NRS, only 2 reported pain severity and 3 reported neuropathy severity with NRS, whereas 9 reported pain and 14 reported neuropathy by VRS. Due to the limited number of NRS scores in our data, we transformed the NRS scores to VRS categories by the following method to increase the statistical power: 0 → none, 1 to 3 → mild, 4 to 6 → moderate, and 7 to 10 → severe.^32,40 We compared the pre- versus post-treatment VRS scores with the Wilcoxon matched-pairs signed-rank test. The pain severity data of 11 patients and the neuropathy severity data of 17 patients were included in the statistical analysis. In addition, we summarized qualitative data of treatment satisfaction with percentages or percentiles (Figure 1). A 2-tailed P-value < .05 was considered statistically significant. Data were analyzed using GraphPad Prism (Version 9.0, GraphPad Software, San Diego, CA, www.graphpad.com).

Results

Demographics and Treatment Completion

Table 1 summarizes the demographics and clinical characteristics. Of the 23 patients analyzed, 17 (74%) identified as female, and 6 (26%) identified as male; 16 (70%) patients identified as White, 4 (17%) as Asian, and 1 (4%) as Black or African American; 2 patients did not report their race (9%). This cohort included 1 (4%) pediatric patient and 22 (96%) adults, with ages ranging between 4 and 85 years (median: 64 years). In 14 (61%) of 23 therapy sessions, 2 or more types of massage were administered to patients. Of the 23 patients, 19 (83%) received Swedish massage as part of their session. Other types of massage administered included reflexology and neuromuscular therapy (Table 1). A total of 23 patients were included in the analysis, including 11 with pain data and 17 with neuropathy data (Figure 1).

Table 1.

Patient Characteristics.

Characteristics	Total (N = 23)
Age, years a	64 (4-85)
Sex
Female	17 (74)
Male	6 (26)
Race
Black or African American	1 (4)
Asian	4 (17)
White	16 (70)
Did not report	2 (9)
Cancer type
Breast cancer	9 (39)
Colorectal cancer	4 (17)
Gynecological cancer	3 (13)
Leukemia	2 (9)
Head and neck cancer	2 (9)
Brain cancer	1 (4)
Popliteal liposarcoma	1 (4)
Neuroblastoma	1 (4)
Chemotherapy status
Completed	19 (83)
Undergoing	4 (17)
Baseline pain severity on a 0-3 VRS scale b	1.9 (0.5)
Baseline neuropathy severity on a 0-3 VRS scale b	1.9 (0.6)
Instances of massage types
Swedish massage	19
Reflexology	13
Neuromuscular therapy	11
Number of massage types during session
1	9 (39)
2	8 (35)
3	6 (26)
Message session duration in minutes
60 min	13 (57)
55 min	1 (4)
45 min	2 (9)
30 min	1 (4)
20 min	3 (13)
Did not report	3 (13)

Data are presented as n (%) except for ^aage expressed as median with range, and ^bbaseline pain severity on a 0 to 3 VRS scale and baseline neuropathy score on a 0 to 3 VRS scale, expressed as mean with standard deviation.

Abbreviation: VRS, verbal rating scale. By the nonparametric model, VRS scores are encoded as 0 = no symptom, 1 = mild, 2 = moderate, and 3 = severe.

Effects of Massage Therapy on CIPN Neuropathy and Pain Scores

Massage therapy was associated with increased numbers of patients with no pain or mild pain and decreased numbers of patients with moderate and severe pain related to CIPN, with 18% of patients (n = 2) reporting mild pain, 73% moderate pain (n = 8), and 9% severe pain (n = 1) before treatment, compared to 64% with no pain (n = 7), 36% with mild pain (n = 4), and 0% with moderate or severe pain after treatment (Figure 2A). All patients’ pain severity decreased from pre-treatment to post-treatment.

Figure 2.

VRS pain severity scores (A) and neuropathy scores (B) at pre- and post-treatment.

Abbreviation: VRS, verbal rating scale.

Massage therapy also increased the number of patients with no or mild neuropathy. It decreased the number of patients with moderate or severe neuropathy, with 24% of patients (n = 3) reporting mild neuropathy symptoms, 65% moderate (n = 11), and 12% severe neuropathy (n = 2) before treatment, compared to 41% reporting no symptoms (n = 7), 47% mild (n = 8), 12% moderate (n = 2), and 0% severe neuropathy after treatment (Figure 2B). All patients reported a reduction in the severity of neuropathy except 1 patient, who reported no change from pre-treatment to post-treatment.

Compared to pre-treatment, the CIPN pain severity score on a 0 to 3 VRS scale decreased by −1.6 points (95% confidence interval [CI]: −1.9, −1.2) and the neuropathy score by −1.2 points (95% CI: −1.4, −0.9) following the completion of one session of massage therapy. The changes were statistically significant for both VRS pain severity (P = .001) and neuropathy severity score (P < .0001; Figure 3).

Figure 3.

Pre- versus post-treatment pain and neuropathy VRS severity scores by the Wilcoxon matched-pair rank test.

Abbreviation: VRS, verbal rating scale. By the Wilcoxon model, VRS scores were encoded as 0 = no symptom, 1 = mild, 2 = moderate, and 3 = severe.

*** indicates P < .005; **** indicates P < .0001.

Satisfaction With Massage Therapy

According to the interview immediately post-treatment, the verbal feedback from 22 out of 23 patients was positive, with comments such as “hand numbness much improved,” “symptoms reduced,” “great treatment,” and “thankful for treatment,” expressing satisfaction and gratitude for treatment and the improvement of symptoms (Table 2).

Table 2.

Patient-reported satisfaction with CIPN symptom relief by massage therapy.

Patient feedback themes	Total (N = 23)
General positive response to treatment	5 (22)
Reduction in neuropathy symptoms (hands)	2 (9)
Reduction in neuropathy symptoms (general)	1 (4)
Reduction in any symptoms	6 (26)
Expressed gratitude for the treatment	12 (52)

Data are presented as n (%).

Discussion

CIPN negatively affects cancer patients’ quality of life and may disturb active treatment. Using real-world data acquired from an integrative oncology program, this retrospective cohort study demonstrated the preliminary efficacy of massage therapy in improving CIPN-related pain and neuropathy among patients with moderate-to-severe CIPN during or after chemotherapy; qualitative data showed that patients were satisfied with the treatment and reported symptom relief. Our findings point to massage therapy’s potential in caring for patients experiencing CIPN symptoms and highlight critical elements to be properly addressed by future trials in the oncological setting.

This study provides important clinical data to support the promising effect of massage therapy on CIPN relief. Our finding is consistent with a previous study showing that patients experienced CIPN symptom improvements following one Swedish massage session. ¹⁹ Studies with more intervention sessions also reported significant reductions in CIPN-related symptoms, such as pain and sleep disturbance, after treatments with Swedish massage, foot massage, or reflexology.^18,20,41 Aside from pain reduction, 2 trials measured the effect of massage therapy on motor (weakness, cramps, ability to hold objects) and autonomic symptoms (dizziness, vision) but demonstrated no significant improvements compared to standard care. ⁴²

Our study has limitations. First, this study is a retrospective cohort study, which is limited in delineating causation. The findings are hypothesis-generating and critical to inform future trial design. Second, this study has no control arm, so the nonspecific effect cannot be separated from the specific effect of the intervention. Third, the individualized intervention protocol reflects the real-world practice of massage therapy but lacks standardization. Future studies need to elucidate the optimal therapeutic parameters of massage therapy, including massage type, treatment frequency, duration, and practitioner qualification, to effectively alleviate CIPN symptoms. Further, we could not capture the detailed characteristics of each participant’s chemotherapy regimen, which may confound the observed effect of massage therapy. Fourth, the sample size is small, from a single cancer institution, and most patients were women, thus limiting the generalizability of our results. Finally, this study only included patient-reported outcome measures, causing measuring bias. Future studies should combine objective and subjective outcome measures, such as the Brief Pain Inventory, PainDetect, quantitative sensory testing, and functional outcome assessments, to efficiently evaluate the clinical effect of the intervention.

Conclusion

Among people with cancer experiencing CIPN, massage therapy may have a short-term impact on improving neuropathy and CIPN pain symptoms. However, this preliminary finding requires further rigorous verification in future randomized controlled clinical trials.