Treatment of lymphedema in patients with advanced cancer receiving palliative care: A single center experience

doi:10.21203/rs.3.rs-2962637/v1

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Treatment of lymphedema in patients with advanced cancer receiving palliative care: A single center experience

https://doi.org/10.21203/rs.3.rs-2962637/v1

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Purpose

Lymphedema can develop during the progression of neoplastic diseases and is a devastating complication in patients with cancer receiving palliative care. This study aimed to investigate the course of treatment for lymphedema in patients receiving palliative care to assess post-treatment outcomes.

Methods

This single-center, retrospective cohort study reviewed the maintained database of patients with lymphedema who presented to our department between January 2015 and December 2022. A combination of skin care, compression therapy, and lymphaticovenular anastomosis was used to treat lymphedema in patients with cancer receiving palliative care. The upper or lower extremity lymphedema indices, calculated based on five upper or four lower extremity circumferences and body mass index, were compared at the first and last visits.

Results

Of the 202 patients with lymphedema, 38 patients with 45 limbs (upper extremities: 11 patients, 12 limbs; lower extremities: 27 patients, 33 limbs) were included in the analysis. There were no significant changes in edema based on the upper or lower extremity lymphedema indices in the upper (p = 0.931) or lower extremities (p = 0.767) between the first and last visits. No pain relief was observed after the treatment. In the treatment differences, the rate of change in edema was − 3.6 ± 10.8% for the compression garment and + 5.7 ± 11.5% for the lymphaticovenular anastomosis, showing no significant difference (p = 0.157).

Conclusion

All treatments had limited therapeutic effects, such as reduced edema and pain relief, and there were no significant differences between them.

palliative care

upper extremity lymphedema

lower extremity lymphedema

lymphaticovenular anastomosis

compression therapy

advanced cancer

Lymphedema is the accumulation of abnormal tissue fluid resulting from impaired lymphatic drainage, and is predominantly cancer-related due to surgery and/or radiation therapy [1]. Upper extremity lymphedema (UEL) is most often caused in breast cancer and lower extremity lymphedema (LEL), in gynecologic cancer [2]. Additionally, lymphoedema can develop in the progression of neoplastic diseases, with reports of edema including lymphedema in 11% of patients with cancer receiving palliative care [3]. It is a devastating complication for patients with cancer, and previous studies have found that patients with cancer and lymphedema were more likely to have a lower quality of life (QOL) and greater emotional distress than those without lymphedema [4–6].

The therapeutic interventions for lymphedema in patients receiving palliative care are limited, and the primary goal is to improve the patient's QOL rather than reducing edema.⁶ However, there is no established care or treatment for lymphedema in patients receiving palliative care to improve their QOL or the related knowledge or understanding among the majority of health professionals. Therefore, we treated lymphedema in patients according to their condition at our hospital based on the hypothesis that the alleviation of edema leads to an improvement in symptoms and QOL. Our treatments included skin care and compression therapy, which are parts of complete decongestive therapy (CDT), and lymphaticovenular anastomosis (LVA), which is a surgical treatment. Although LVA is a safe and effective treatment [7, 8], only non-surgical treatments, such as CDT, have been reported for the treatment of lymphedema in patients receiving palliative care [6]. Additionally, not only is the therapeutic efficacy of LVA for patients receiving palliative care unknown, but also there is a significant lack of information regarding the treatment course of lymphedema for other treatments.

Consequently, this study investigated the course of treatment for lymphedema in patients receiving palliative care with the aim of evaluating post-treatment outcomes and identifying best practices.

Study design

This single-center retrospective cohort study was conducted in accordance with the Declaration of Helsinki as revised in 2013 and was approved by our hospital’s institutional review board. We retrospectively reviewed the data of patients with lymphedema who presented to our department between January 2015 and December 2022.

Participants

Inclusion criteria were: presence of cancer-related lymphedema requiring palliative care and treated for lymphedema in our department. Exclusion criteria were: (1) diagnosis of edema other than lymphedema, such as hypoproteinemia, chronic renal failure, or deep vein thrombosis; (2) age < 18 years; and (3) significant cognitive or psychiatric disorders.

All patients received self-care instructions centered on skincare under the guidance of a trained lymphatic therapist. For compression therapy, easy-to-wear low-pressure compression garments are often applied, whereas standard-pressure ones are applied depending on the patient's clinical state. In this study, standard-pressure compression garments were adjusted to a pressure of 20–30 mmHg, and low-pressure ones were used with elasticated tubular support bandages (tg grip, NAK Corporation, Osaka, Japan) at pressures of less than 20 mmHg. LVA was only performed in patients with a stable clinical status who wished to undergo surgery with the permission of their palliative care physician. Multisite LVA with a small incision (approximately 1.5 cm) based on lymphatic mapping provided by indocyanine green imaging was performed under local anesthesia. The lymphatic vessels and size-matched venulae were anastomosed using 11 − 0 or 12 − 0 nylon. Compression therapy was resumed three days after LVA using low-pressure compression garments. All patients were followed-up every 1–2 months as much as possible depending on their general condition. The above treatments were performed considering the patients' conditions and respecting their wishes.

Measurement

The patients were classified into two groups: UEL and LEL, and data were collected on basic patient characteristics, etiology, cancer treatment information, lymphedema and treatment information, and circumference values at specific points of the affected limb.

Quantitative variables

The circumference of the affected limb was measured at five points in the upper extremity (dorsum manus, wrist, 5 cm from the cubital fossa in the forearm, 10 cm from the cubital fossa in the upper arm, and axilla), and four points in the lower extremity (foot, ankle, 5 cm below the knee, and 10 cm above the knee). This was measured in the supine position at the first and last visits by the lymphatic therapist engaged with the patient. Changes in lymphedema volume at the first and last visits were assessed using the UEL or LEL index. The indices were calculated by dividing the sum of the squared circumference at five points in the upper extremity or four points in the lower extremity by the body mass index (BMI) [9, 10]. Changes in edema since the last visit were evaluated from medical records. The rate of change in edema between the first and last visits due to the different treatment methods was measured using the following formula:

[(UEL or LEL index at first visit)–(UEL or LEL index at last visit)] × 100 / (UEL or LEL index at first visit).

Statistical analysis

Continuous variables are presented as means ± standard deviations, and categorical variables, as frequencies and percentages. UEL and LEL groups were not compared, but changes in edema within groups and between treatment methods were compared using a two-tailed Student’s t-test. Statistical significance was set at p < 0.05.

Overall, 202 patients with lymphedema (101 in the UEL and LEL groups each) were identified during the study period, and 38 met the inclusion criteria. Of them, 11 patients (12 limbs) were in the UEL group and 27 patients (33 limbs) in the LEL group (Fig. 1). The proportion of patients receiving palliative care in the LEL group (26.7%) was higher than that in the UEL group (10.9%). The average age of the patients was 67.7 ± 14.8 years, with the majority (73.7%) being female, and BMI was 24.4 ± 4.6 kg/m². The stage of cancer of all patients was IV; the etiology of UEL was breast cancer (100%), and that of LEL was mostly gynecological cancer (44.4%) (Table 1). The International Society of Lymphology (ISL) stages [11] of all patients were almost evenly distributed from stages I to IIB. Overall patient mortality rate was 92.1%, with a mean follow-up period of 2.5 ± 3.4 months and a mean time from first visit to death of 6.5 ± 6.9 months.

Table 1

Characteristics of patients in upper and lower extremity lymphedema groups.
		Total	UEL	LEL
Number of patients		38	11	27
Number of affected limbs		45	12	33
Affected limb	Right	24 (53.3%)	4 (33.3%)	20 (60.6%)
Affected limb	Left	21 (46.7%)	8 (66.7%)	13 (39.4%)
Age (years)		67.7 ± 14.8	65.5 ± 16.6	68.7 ± 13.7
Gender	Male	10 (26.3%)	1 (9.1%)	9 (33.3%)
Gender	Female	28 (73.7%)	10 (90.9%)	18 (66.7%)
BMI (kg/m²)		24.4 ± 4.6	20.3 ± 2.1	23.9 ± 4.2
Smoking		13 (34.2%)	3 (27.3%)	10 (37.0%)
Diabetes		2 (5.3%)	0 (0%)	2 (7.4%)
Etiology			Breast cancer = 11 (100%)	Gynecologic cancer = 12 (44.4%), urological cancer = 7 (25.9%), other cancer = 8 (29.6%)
Cancer stage = IV		38 (100%)	11 (100%)	27 (100%)
Lymph node dissection		14 (36.8%)	9 (75.0%)	5 (18.5%)
Cancer treatment	Radiotherapy	28 (73.7%)	8 (72.7%)	20 (74.1%)
Cancer treatment	Chemotherapy	31 (81.6%)	9 (81.8%)	22 (81.5%)
Mean time from cancer surgery to first visit (years)		7.2 ± 7.0	10.7 ± 8.0	3.4 ± 2.1
Mean time from onset of edema to first visit (months)		15.6 ± 37.1	42.4 ± 61.8	5.2 ± 6.6
History of cellulitis		5 (11.1%)	2 (16.7%)	3 (9.1%)
Pain		19 (50.0%)	4 (36.4%)	15 (55.6%)
ISL stage	I	15 (33.3%)	7 (58.3%)	8 (24.2%)
	IIA	16 (35.6%)	2 (16.7%)	14 (42.4%)
	IIB	13 (28.9%)	2 (16.7%)	11 (33.3%)
	III	1 (2.2%)	1 (8.3%)	0 (0%)
Mortality		35 (92.1%)	11 (100%)	24 (88.9%)
Mean time from first visit to death (months)		6.5 ± 6.9	8.3 ± 4.7	5.7 ± 7.6
Mean follow-up (months)		2.5 ± 3.4	3.5 ± 3.7	2.1 ± 3.2
UEL, upper extremity lymphedema; LEL, lower extremity lymphedema; ISL, International Society of Lymphology.

The treatment and outcomes of UEL and LEL groups are shown in Table 2. All patients underwent self-care centered on skin care, and low-pressure compression garments were the most common treatment for UEL (50.0%) and LEL (63.6%). LVA was performed in one patient in the UEL group (8.3%) and four patients in the LEL group (12.1%). There were no significant changes in edema in the UEL (p = 0.931) or LEL (p = 0.767) groups between the first and last visits. Pain was present in 36.4% of patients with UEL and 55.6% of patients with LEL at the first visit; however, no relief was observed after treatment. Based on the chart review, edema had increased for most patients in the UEL (66.7%) and LEL groups (69.7%) since their last visits (Fig. 2).

Table 2

Treatment and outcomes for upper and lower extremity lymphedema.
		UEL	LEL
Treatment	Skin care only	2 (16.7%)	8 (24.2%)
	Low-pressure compression garment + skin care	6 (50.0%)	21 (63.6%)
	Standard-pressure compression garment + skin care	3 (25.0%)	0 (0%)
	Surgery (LVA) + low-pressure compression garment + skin care	1 (8.3%)	4 (12.1%)
UEL/LEL index	First visit	120.9 ± 16.8	185.4 ± 27.0
	Last visit	120.1 ± 22.4	182.3 ± 39.0
	p value	0.931	0.767
Pain relief		0 (0%)	0 (0%)
Change in edema from last visit	Increase in edema	8 (66.7%)	23 (69.7%)
	(Generalized edema)	[2 (16.7%)]	[3 (9.1%)]
	(Lymphorrhea)	[1 (8.3%)]	[2 (6.1%)]
	No change in edema	1 (8.3%)	8 (24.2%)
	Reduction in edema	1 (8.3%)	1 (3.0%)
	Unknown	2 (16.7%)	1 (3.0%)
UEL, upper extremity lymphedema; LEL, lower extremity lymphedema; LVA, lymphaticovenular anastomosis.

Changes in edema due to different treatment methods are shown in Table 3. Patients who only performed self-care centered on skincare were not followed up. The rate of change in edema between the first and last visits was − 3.6 ± 10.8% for the compression garment and + 5.7 ± 11.5% for the LVA with compression garment, indicating no significant difference (p = 0.157).

Table 3

Changes in edema due to different treatment methods.
	Compression garment (n = 18)	LVA with compression garment (n = 4)	p value
Edema rate of change*	-3.6 ± 10.8%	+ 5.7 ± 11.5%	0.157
Mean follow-up (months)	4.2 ± 3.4	3.5 ± 3.9	0.745
*[(UEL or LEL index at first visit)–(UEL or LEL index at last visit)] × 100 / (UEL or LEL index at first visit)
UEL, upper extremity lymphedema; LEL, lower extremity lymphedema; LVA, lymphaticovenular anastomosis.

Patients with cancer receiving palliative care often cannot tolerate a full evaluation and treatment for lymphoedema, suggesting the need to develop appropriate palliative approaches [6]. Although the mean follow-up period in this study was short at 2.5 ± 3.4 months, our findings indicated that the therapeutic effect of the treatments of edema did not differ significantly. In other words, there was no significant reduction in edema or pain relief during the follow-up period regardless of the treatment strategy. Although LVA has been shown to be an effective and versatile procedure for the treatment of lymphedema [7, 8], the change in edema was increased by + 5.7 ± 11.5% in the group treated with LVA and compression garment. This was probably due to an increase in edema with the progression of the neoplastic disease, suggesting that LVA does not have sufficient therapeutic efficacy for lymphedema in advanced cancers.

Based on our results, although LVA is a minimally invasive surgery, it is more burdensome than other treatments and may be an inappropriate therapeutic strategy. However, all five patients who underwent LVA were satisfied with their treatment and could not completely rule out LVA as a treatment option. Lymphedema can substantially impact the physical experience and psychosocial status of patients receiving palliative care [12]. Professional lymphedema management in palliative care can be neglected, leading to hopelessness and disgust in patients [6]. In such a psychological situation, the fact that they underwent surgery (LVA) may have led to gratitude and satisfaction in our patients. Patient satisfaction should be evaluated in more detail in future studies and compared with other treatments.

CDT consists of four components: skin care, exercise, manual lymphatic drainage, and compression therapy [13]. It is the most frequently recommended management modality for lymphedema; one study with a small sample size indicated improvements in limb volume, skin quality, and lymphedema-related QOL for CDT in patients with cancer receiving palliative care [14]. However, CDT should be adapted in a palliative setting for patients with advanced cancers according to their treatment tolerance. In this study, skin care and compression therapy were used for lymphedema in most patients receiving palliative care (91.7% in the UEL group and 87.9% in the LEL group). A reduction in edema of -3.6 ± 10.8% was observed with compression therapy using compression garments, even though most of the garments had low pressure (66.7% and 100% in the UEL and LEL groups, respectively). Compression garments are more effective at higher pressures; however, patients receiving palliative care often have difficulty wearing standard pressure garments. Elasticated tubular support bandages, although low-pressure compression garments, are low-cost, easy to slip on, and provide treatment that patients can tolerate even when their general conditions worsen. Although two reports of compression therapy applied to patients receiving palliative care had major limitations because they were case reports, both yielded positive results, including a reduction in edema [15, 16]. Low-pressure compression garments such as elasticated tubular support bandages may be an effective treatment that is easy to adopt on a daily basis for patients receiving palliative care.

Our results showed that edema increased in most patients (66.7% and 69.7% of those with UEL and LEL, respectively) from the last visit until death, although there were no precise measurements. As some patients had generalized edema or lymphorrhea, it was presumed that the edema had increased considerably. Edema in patients at the end of life may have a multifactorial etiology that includes not only lymphedema due to lymphatic congestion but also a combination of angioedema due to increased capillary hydrostatic pressure, hypoproteinemic edema due to decreased plasma oncotic pressure, and/or permeability edema due to increased capillary permeability [17, 18]. Lymphedema was diagnosed by various examinations at the first visit; however, it is considered that edema increased due to a mixed etiology as the neoplastic disease progressed. Given that edema eventually increases in patients at the end of life, it may not be controlled by treatment or care. Therefore, it may be desirable to present the treatment methods for lymphedema that can be provided at all institutions, respect the patient's wishes, and select the treatment that the patient can tolerate.

Our study has two critical limitations. First, it was a retrospective cohort study with a small sample size and a short follow-up period, which may have caused a significant bias. Second, there was a lack of patient-reported outcomes regarding the symptoms and treatment of lymphedema, which may have affected the interpretation of the results. In particular, it is important to evaluate the improvement in patients’ QOL, which will be considered in future research.

In this study, a combination of skincare, compression therapy, and LVA was used to treat lymphedema in patients with cancer receiving palliative care. None of the treatments had limited therapeutic effects, such as reduction of edema and pain relief, and there was no significant difference among them. Because edema may increase with the progression of neoplastic diseases, treatment and care respecting the patient's wishes are desirable. Although this study could not identify any best practices from the perspective of health professionals, it highlighted the need for established practice guidelines on this topic aimed at improving patients' QOL.

Acknowledgments

We would like to thank Editage (www.editage.com) for the English language editing.

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Keisuke Shimbo and Haruka Kawamoto. The first draft of the manuscript was written by Keisuke Shimbo and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Ethics declarations

Ethics approval

This study was approved by the Research Ethics Committee of Hiroshima Prefectural Hospital (approval number: 202304-4).

Consent to participate

Informed consent was obtained from all individual participants included in the study by opt-out.

Competing interests

The authors declare no competing interests.

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No competing interests reported.

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Treatment of lymphedema in patients with advanced cancer receiving palliative care: A single center experience

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Introduction

Materials and Methods

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Participants

Measurement

Quantitative variables

Statistical analysis

Results

Discussion

Conclusion

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