Internal Lymphedema Research Articles

Patient-reported outcome measures and physical function following head and neck lymphedema - a systematic review.

Head and neck cancer (HNC) treatments often lead to significant morbidity, including lymphedema. This systematic review aims to comprehensively explore the prevalence and impact of head and neck lymphedema (HNL) following treatment. A systematic literature search was conducted up to September 2023. Studies evaluating HNL prevalence, associated factors, impact, patient-reported outcomes (PROMs), and physical assessments were included. Methodological quality assessment was performed, and data were synthesised narratively. Twelve studies met the inclusion criteria, with methodological quality ranging from moderate to high. Internal lymphedema prevalence was consistently higher than external lymphedema, with varying rates attributed to treatment modalities and assessment methods. PROMs such as the Lymphedema Symptom Intensity and Distress-Head and Neck and physical assessments including Patterson's Rating Scale were commonly utilised. HNL significantly impacted quality of life and physical function, with reported symptoms including discomfort, tightness, swallowing difficulties, and psychological distress. HNL is a common sequela of HNC treatment with significant implications for individuals' QoL. Standardised assessment protocols and tailored interventions are needed to address the needs of individuals with HNL and improve overall outcomes. This systematic review highlights a significant prevalence of lymphedema, particularly internal lymphedema in the larynx and pharynx, following treatment. Swallowing difficulties, nutritional issues, anxiety, depression, and body image concerns were associated with both internal and external lymphedema. The impact on quality of life is substantial, with survivors experiencing physical symptoms and psychosocial challenges, emphasising the importance of integrated care approaches tailored to both aspects of well-being.

Clinical, Pathologic, and Dosimetric Predictors of Head and Neck Lymphedema Following Definitive or Adjuvant Radiation Therapy for Head and Neck Cancer

Head and neck lymphedema (HNL) following radiation therapy for head and neck cancer (HNC) causes patient morbidity. Predicting individual patients' risk of HNL after treatment is challenging. We aimed to identify the demographic, disease-related, and treatment-related factors associated with external and internal HNL following treatment of HNC with definitive or adjuvant radiation therapy. Relevant clinical, pathologic, and dosimetric data for 76 consecutive patients who received definitive or adjuvant radiation ± chemotherapy were retrospectively collected from a single institution. Multivariable models predictive of external and internal lymphedema using clinicopathologic variables alone and in combination with dosimetric variables were constructed and optimized using competing risk regression. After median follow-up of 550 days, the incidence of external and internal HNL at 360 days was 70% and 34%, respectively. When evaluating clinical and treatment-related factors alone, number of lymph nodes removed and advanced adenopathy status were predictive of external lymphedema. With incorporation of dosimetric variables, the optimized model included the percentage volume of the contralateral lymph node level VII receiving 30Gy V30 ≥50%, number of lymph nodes removed, and advanced adenopathy status. For internal lymphedema, our clinicopathologic model identified both adjuvant radiation, as opposed to definitive radiation, and advanced adenopathy status. With inclusion of a dosimetric variable, the optimized model included larynx V45 ≥50% and advanced adenopathy. HNL following HNC treatment is common. For both external and internal lymphedema, nodal disease burden at diagnosis predicts increased risk. For external lymphedema, increasing extent of lymph node dissection prior to adjuvant therapy increases risk. The contralateral level VII lymph node region is also predictive of external lymphedema when radiation dose to V30 is ≥50%, meriting investigation. For internal lymphedema, we confirm that increasing radiation dose to the larynx is the most significant dosimetric predictor of mucosal edema when larynx V45 is ≥50%.

Internal Lymphedema Response to A Single Session of External Advanced Pneumatic Compression in Head and Neck Cancer Survivors

Internal Lymphedema Response to A Single Session of External Advanced Pneumatic Compression in Head and Neck Cancer Survivors

Implementing flexible endoscopic evaluation of swallow screening within annual cancer surveillance appointments to monitor for late-stage radiation-induced dysphagia: A feasibility study.

Late-stage progressive decline of swallowing function after radiotherapy for head and neck cancer (HNC) is often difficult to monitor. This study examined the feasibility and clinical outcomes of speech-language pathology implementing flexible endoscopic evaluation of swallow (FEES) screening during annual cancer surveillance visits to monitor late-stage swallowing function. Patients >2 years post treatment who attended routine oncological visits underwent FEES screening. Feasibility (service data, stakeholder survey) and swallowing outcomes (oral intake, secretions, internal lymphedema, penetration-aspiration, and residue) were collected. Screening was completed with 70% (50/71) of eligible patients. Medical staff and speech-language pathologists indicated the protocol was worthwhile and achievable to incorporate into practice. Almost all patients were willing to complete the protocol annually. FEES outcomes identified 84% with dysphagia versus only 26% self-reported dysphagia. Findings indicate FEES screening incorporated into annual oncological reviews is feasible and effective at monitoring late-stage swallowing function following HNC.

Longitudinal Pattern of Lymphedema and Fibrosis in Patients With Oral Cavity or Oropharyngeal Cancer: A Prospective Study

PurposeThe study aimed to describe the prevalence, severity, and trajectory of internal lymphedema, external lymphedema, and fibrosis in patients with oral cavity or oropharyngeal (OCOP) cancer. Methods and Materials120 patients with newly diagnosed OCOP cancer were enrolled in a prospective longitudinal study. Recruitment was conducted at a comprehensive medical center. Participants were assessed at pre-treatment, end-of-treatment, 3-, 6-, 9-, and 12-month post-cancer treatment. Validated clinician-reported measures and CT imaging were used to assess the study outcomes. Results76 patients who completed the 9- or 12-month assessments were included in this report. 1) External lymphedema and fibrosis trajectories: The total severity score peaked between end-of-treatment and 3 months post-treatment; reduced gradually over time but did not return to baseline by 12 months post-treatment (p < .001). The longitudinal patterns of severity scores for patients treated with surgery only or with multimodality therapy were similar. 2) Internal swelling trajectories: All patients demonstrated a significant increase in sites with swelling immediately post-treatment. For patients treated with surgery only, swelling was minimal and returned to baseline by 9- to 12 months post-treatment. Patients receiving multi-modal treatment demonstrated a gradual decrease in number of sites with swelling during the 12-month post-treatment period yet remained significantly above baseline (p < .05). 3) CT imaging: Different patterns of changes in prevertebral soft tissue and epiglottic thickness were observed in the surgery-only and multimodality treatment groups during the 12-month post-treatment period. There were minimal changes in thickness in either region in the surgery-only group. Patients with multi-modal treatment had significant increases in thickness in both regions 3 months post-treatment which remained thicker at 12 months than it was at baseline (p <.001). ConclusionLymphedema and fibrosis are common complications of OCOP cancer therapy. Routine assessment, monitoring, and timely treatment of lymphedema and fibrosis are critical.

Survivorship profile and post-treatment quality of life of oral cancer survivors in comparison with caregivers: An analysis of a real-world cohort of a developing country.

e18036 Background: Oral cavity cancer is the second most common cancer in India; India bears the most burden of oral cancer in the world. The most effective way to study the effectiveness of treatments is in clinical trials, but the quality of life (QOL) and post-treatment effects of those treatments are seldom studied in real-world settings. Methods: All oral cancer survivors treated with curative intent at our institute from September 2019 to January 2021, who were disease-free for a minimum of six months following treatment, were included in this study. The QOL of these cancer survivors was compared with that of their caregivers using the WHOQOL BREF questionnaire. The complete survivorship profile was evaluated using a Constant shoulder score for shoulder dysfunction, clinical oral dryness score (CODS) for xerostomia, Sydney Swallow Questionnaire (SSQ) for swallowing dysfunction, Patterson scale for lymphedema, Comprehensive Score for financial Toxicity (COST)‐Functional Assessment of Chronic Illness Therapy (FACIT) questionnaire for financial toxicity, Depression, Anxiety and Stress Scale - 21 Items (DASS-21) for psychological wellbeing. Results: A total of seventy-nine survivors were included. The median age was 49 years. Though both survivors and caregivers had similar QOL scores in the physical and environmental domains, survivors had poor scores in the social (M = 58.7,SD = 21.9) and psychological domains (M = 60.4,SD = 15.6). The T stage (p = 0.06), surgery (p = 0.008), and trismus (p = 0.03) were significant factors affecting swallowing. Those patients who had undergone selective neck dissection had better shoulder scores compared to those who had modified radical neck dissection (p = 0.006). 75% of people had xerostomia and 10.9% had severe xerostomia. Internal lymphedema was seen in 30.4% of people. Depression and anxiety were recorded in 46 (58.2%) and 33 (41.8%) patients respectively. Employment status (p = 0.04) and treatment modality (p = 0.05) were significant factors affecting financial toxicity. Conclusions: Oral cancer survivors had a poor psychosocial QOL compared to their caregivers. Treatment-related functional sequelae had a significant negative impact on quality of life across all domains. Clinical trial information: CTRI/2020/07/026848.

The efficacy of Kinesio taping on lymphedema following head and neck cancer therapy: a randomized, double blind, sham-controlled trial

Objective The aim was to investigate the effectiveness of Kinesio taping for lymphedema following head and neck cancer therapy and its effect on patient compliance and quality of life. Methods A total of 66 patients with lymphedema following head and neck cancer therapy were randomly allocated to the therapeutic Kinesio taping group (n = 33) and the sham Kinesio taping group (n = 33). All participants received manual lymphatic drainage, Kinesio taping, and home exercises for the first four weeks, and only home exercises for the second four weeks. The tape measurements, a scale of external lymphedema, a scale of the internal lymphedema, and quality of life were evaluated in both groups. The perceived discomfort consisting of limitation of daily living activities, pain, tightness, stiffness, and heaviness were also recorded. Results When the group x time effect was evaluated, it was observed that external lymphedema was significantly reduced in both groups according to neck and face composite measurements (p < .001). However, in these measurements, a significant difference was found between the groups in favor of the KT group (p = .001, p = .032, respectively). At the end of the study, there was no significant difference in terms of internal lymphedema in both groups (p = .860). The quality of life parameters such as global health status and swallowing were significantly better in the Kinesio taping group (p < .001). There was no significant difference in the parameters of perceived discomfort between the two groups (p = .282, p = .225, p = .090, p = .155, p = .183, respectively). Conclusion Kinesio taping is effective in tape measurements and positively affects the quality of life in lymphedema following head and neck cancer therapy.

Managing hidden late complications in irradiated head and neck cancer patients using a practical integrative approach: a narrative review

: Radiation techniques have evolved in the last twenty years towards ubiquitous use of intensity modulated radiation therapy (IMRT), which has decreased late complications from radiation to the head and neck area. Despite this, devastating sequelae still impair the long-term functioning of head and neck patients. There are the well-known sequelae of trismus, osteoradionecrosis and xerostomia. However, inadequately addressed sequalae such as dysphagia, odynophagia, hypoguesia, internal lymphedema and cognitive impairment do significant hidden damage to patients’ quality of life (QOL). Research has demonstrated that QOL can continue to decline even 10 years post radiation treatment, when many clinicians have long since ended follow-ups. Patients often underreport these symptoms and physicians are not trained to specifically ask about these symptoms long-term. This paper will use an evidence-based approach to look at the hidden sequelae of radiation to the head and neck area, review the current data regarding integrative approaches, and provide a practical integrative system for the practicing clinician. A practical system would include exercise, psychosocial techniques for the mind and emotions, meditation and early referral to a registered dietitian nutritionist (RDN) to educate and support the patients’ nutritional needs. Integrative techniques have been shown in the literature to provide an increased QOL and also in some studies, a direct improvement in patients’ recurrence rates and mortality. If more providers were to understand and put more emphasis on early integrative interventions, it could improve long-term head and neck cancer QOL and mortality outcomes after radiation.

Association between external and internal lymphedema and chronic dysphagia following head and neck cancer treatment.

To examine the relationship between chronic external and internal head and neck lymphedema (HNL) and swallowing function in patients following head and neck cancer (HNC) treatment. Seventy-nine participants, 1-3 years post treatment were assessed for external HNL using the MD Anderson Cancer Centre Lymphedema Rating Scale, and internal HNL using Patterson's Radiotherapy Edema Rating Scale. Swallowing was assessed via instrumental, clinical and patient-reported outcome measures. HNL presented as internal only (68%), combined external/internal (29%), and external only (1%). Laryngeal penetration/aspiration was confirmed in 20%. Stepwise multivariable regression models, that accounted for primary site, revealed that a higher severity of external HNL and internal HNL was associated with more severe penetration/aspiration (P < .004 and P = .006, respectively), diet modification (P < .001 both), and poorer patient-reported outcomes (P = .037 and P = .014, respectively). Increased swallowing issues can be expected in patients presenting with more severe external HNL and/or internal HNL following HNC treatment.

Prevalence of external and internal lymphedema secondary to head and neck cancer treatment

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Patients of head and neck cancer are at risk of developing secondary lymphedema after being treated for head and cancer. The purpose of this study was to examine the prevalence of secondary head and neck (HNL) lymphedema in post treated patients of head and neck cancer (HNC).&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This was a prospective observational study including 48 head and neck cancer patients who were atleast 3 months post treatment. The present study was conducted in the department of ENT, GMC Jammu for a period of 1 year from February 2018 to March 2019.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; Forty patients (43.34%) were males and 8 were females with age ranging from 25 to 82 years. 58.33% patients in our study had some form of lymphedema. Out of these patients, 21.43% had only external lymphedema, 35.71% had only internal lymphedema and 42.86% had combined lymphedema.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Lymphedema should be examined in the patients with head and neck cancer patients.&lt;/p&gt;

Biomarkers Associated with Lymphedema and Fibrosis in Patients with Cancer of the Head and Neck.

This study examined interrelationships of selected interleukins (ILs), tumor growth factors, matrix metalloproteinases (MMPs), and C-reactive protein, interferon-gamma (IFN-γ), and tumor necrosis factor α (TNF-α) with lymphedema/fibrosis in patients with head and neck cancer (HNC). Patients newly diagnosed with ≥Stage II HNC (N = 100) were assessed for external/internal lymphedema and/or fibrosis before treatment, end-of-treatment, and at regularly established intervals through 72 weeks posttreatment and blood was drawn. Data from 83 patients were analyzed. Group-based trajectory modeling generated patient groups with similar longitudinal biomarker and lymphedema-fibrosis trajectories. Area-under-the-curve (AUC) values were also generated for each biomarker and severity of lymphedema-fibrosis. Associations among and between biomarkers and lymphedema-fibrosis trajectories and AUCs were tested (log-likelihood chi-square, correlations). The strongest evidence for the association of biomarkers with the overall and trajectory patterns and severity of lymphedema-fibrosis was observed for IL-6, IL-1β, TNF-α, TGF-β1, and MMP-9 (all p < 0.05). Convergence of joint trajectory patterns and AUC were observed with IL-6 with all lymphedema-fibrosis trajectories and internal lymphedema AUC. IL-1β trajectories converged with external lymphedema trajectories and all lymphedema-fibrosis AUCs. TNF-α and TGF-β1 converged most strongly with fibrosis in terms of trajectory patterns. However TNF-α demonstrated stronger association with lymphedema-fibrosis AUC (fibrosis: rs = 0.49). MMP-9 demonstrated convergence with lymphedema-fibrosis AUCs (lymphedema: 0.43-0.42; fibrosis: 0.35). Systemic levels of selected mediators of proinflammatory processes track with acute and chronic clinical phenotypes of lymphedema/fibrosis in HNC patients suggesting their potential role in the pathogenesis of these conditions.

A Prospective Study of the Lymphedema and Fibrosis Continuum in Patients with Head and Neck Cancer.

The purpose of this study was to determine the prevalence and nature of internal, external, and combined lymphedema and fibrosis in patients with head and neck cancer (HNC). We obtained consent from 100 patients newly diagnosed with having cancer of the head and neck for a 4-year, prospective, longitudinal descriptive study. Recruitment began in August 23, 2010, and the study was completed in April 24, 2014. Eighty-three were evaluated at regular intervals from preradiation therapy to 18 months post-treatment. Percentage developing external, internal, or both types of lymphedema and/or fibrosis and trajectories of the severity of external, internal, or both types of lymphedema and/or fibrosis were determined. Before treatment, lymphedema rates were the following: external: 62.7%, internal: 41.7%, or combined: 29.2%, and/or fibrosis: 42.2%. Ranges of lymphedema late-effect rates were even higher: external: 81.9%-90.1%, internal: 80.4%-89.4%, combined: 70.6%-80.9%, and fibrosis: 66.7%-77.4%. Approximately 75% had a late-effect trajectory characterized by moderate to severe external or internal lymphedema; ∼47% had moderate to severe fibrosis. Lymphatic and soft tissue complications of HNC occur not only post-treatment but also before treatment. They are ubiquitous throughout the first 18 months post-treatment, with greater than 90% of patients in our study experiencing some form of internal, external, or combined lymphedema, and over half of those patients developing fibrosis. Further research regarding these conditions is indicated.

Internal Lymphedema Correlates with Subjective and Objective Measures of Dysphagia in Head and Neck Cancer Patients.

Tumor/treatment-related internal lymphedema (IL) and/or external lymphedema (EL) are associated with functional deficits and increased symptom burden in head and neck cancer patients (HNCP). Previously, we noted association between EL/IL and patient-reported dysphagia using the Vanderbilt Head and Neck Symptom Survey (VHNSS) version 1.0. To determine the relationship between IL/EL and subjective and objective measures of swallowing function. Eighty-one HNCP completed: (1) VHNSS version 2.0, including 13 swallowing/nutrition-related questions grouped into three clusters: swallow solids (ss), swallow liquids (sl), and nutrition(nt); (2) physical assessment of EL using Foldi scale; (3) endoscopic assessment of IL using Patterson scale (n = 56); and (4) modified barium swallow study rated by dysphagia outcome and severity scale (DOSS) and in conjunction with a swallow evaluation by National Outcomes Measurement System (NOMS). Examinations were performed at varied time points to assess lymphedema spectrum, from baseline (n = 15, 18.1%) to 18 months post-therapy (n = 20, 24.1%). VHNSS swallow/nutrition items scores correlated with NOMS/DOSS ratings (p < 0.001). Highest correlation was with NOMS: ss (-0.73); sl (-0.61); nt (-0.56). VHNSS swallow/nutrition scores correlated with maximum grade of swelling for any single structure on Patterson scale: ss (0.43; p = 0.001); sl (0.38; p = 0.004); nt (0.41; p = 0.002). IL of aryepiglottic/pharyngoepiglottic folds, epiglottis, and pyriform sinus were most strongly correlated with VHNSS and NOMS ratings. NOMS/DOSS ratings correlated with EL (> = -0.34; p < 0.01). No meaningful correlations exist between VHNSS swallow/nutrition items and EL (< ± 0.15, p > 0.20). IL correlated with subjective and objective measures of swallow dysfunction. Longitudinal analysis of trajectory and impact of IL/EL on dysphagia is ongoing.

Differences of symptoms in head and neck cancer patients with and without lymphedema.

Head and neck cancer (HNC) patients are at risk for developing external and internal lymphedema. Currently, no documentation of symptom differences between individuals with and without head and neck lymphedema is available. The purpose of this analysis was to examine symptom differences among HNC patients with and without lymphedema. Data were drawn from three cross-sectional studies of HNC patients >3months post-cancer treatment (total N = 163; 128 patients with lymphedema, 35 without lymphedema). External lymphedema was evaluated via physical examination; internal lymphedema was identified through endoscopic examination. Participant's head and neck lymphedema status was categorized into two groups: no indication of external or internal lymphedema and at least some indication of external or internal lymphedema. Lymphedema Symptom Intensity and Distress Survey-Head and Neck (LSIDS-H&N) was used to assess symptom burden. Descriptive statistics, McNemar, chi-squared, Wilcoxon signed-ranks, and Mann-Whitney tests were used. Twenty-three pairs of patients were identified and matched on the age, primary tumor site, tumor stage, and time since end of cancer treatment. Relative to patients without lymphedema, matched patients with lymphedema reported either increased symptom prevalence or severity or distress level for the following symptoms (prevalence differences of at least 15% between the matched groups and p < 0.05): (1) numbness; (2) tightness; (3) heaviness; (4) warmth; (5) pain without head/neck movement; (6) problems swallowing mashed or pureed foods; (7) trouble breathing; (8) blurred vision; (9) feel worse when flying in an airplane; and (10) swelling. Findings suggest that HNC-related lymphedema may be associated with substantial symptom burden. Studies with larger sample sizes are needed to replicate the findings.

Internal lymphedema correlation with subjective and objective measures of dysphagia in head and neck cancer.

6051 Background: Tumor/treatment-related external (EL) and/or internal lymphedema (IL) are associated with functional deficits and increased symptom burden in head and neck cancer (HNC) patients. W...

Impact of secondary lymphedema after head and neck cancer treatment on symptoms, functional status, and quality of life

Lymphedema may disrupt local function and affect quality of life (QOL) in patients with head and neck cancer. The purpose of this study was to examine the associations among severity of internal and external lymphedema, symptoms, functional status, and QOL in patients with head and neck cancer. The sample included 103 patients who were ≥ 3 months after head and neck cancer treatment. Variables assessed included severity of internal and external lymphedema, physical/psychological symptoms, functional status, and QOL. Severity of internal and external lymphedema was associated with physical symptoms and psychological symptoms. Patients with more severe external lymphedema were more likely to have a decrease in neck left/right rotation. The combined effects of external and internal lymphedema severity were associated with hearing impairment and decreased QOL. Lymphedema severity correlates with symptom burden, functional status, and QOL in patients after head and neck cancer treatment.

Factors Associated With External and Internal Lymphedema in Patients With Head-and-Neck Cancer

The purpose of this study was to examine factors associated with the presence of secondary external and internal lymphedema in patients with head-and-neck cancer (HNC). The sample included 81 patients ≥3 months after HNC treatment. Physical and endoscopic examinations were conducted to determine if participants had external, internal, and/or combined head-and-neck lymphedema. Logistic regression analysis was used to examine the factors associated with the presence of lymphedema. The following factors were statistically significantly associated with presence of lymphedema: (1) location of tumor associated with presence of external (P=.009) and combined lymphedema (P=.032); (2) time since end of HNC treatment associated with presence of external (P=.004) and combined lymphedema (P=.005); (3) total dosage of radiation therapy (P=.010) and days of radiation (P=.017) associated with the presence of combined lymphedema; (4) radiation status of surgical bed was associated with the presence of internal lymphedema, including surgery with postoperative radiation (P=.030) and (salvage) surgery in the irradiated field (P=.008); and (5) number of treatment modalities associated with external (P=.002), internal (P=.039), and combined lymphedema (P=.004). No demographic, health behavior-related, or comorbidity factors were associated with the presence of lymphedema in the sample. Select tumor and treatment parameters are associated with increased occurrence of lymphedema in patients with HNC. Larger and longitudinal studies are needed to identify adjusted effects and causative risk factors contributing to the development of lymphedema in patients with HNC.

Prevalence of Secondary Lymphedema in Patients With Head and Neck Cancer

Context Because surgery, radiation, and/or chemotherapy disrupt lymphatic structures, damage soft tissue leading to scar tissue formation and fibrosis, and further affect lymphatic function, patients with head and neck cancer may be at high risk for developing secondary lymphedema. Yet, no published data are available regarding the prevalence of secondary lymphedema after head and neck cancer treatment. Objectives The aim of this study was to examine prevalence of secondary lymphedema in patients with head and neck cancer. Methods The study included 81 patients with head and neck cancer who were three months or more post-treatment. External lymphedema was staged using Foldi's lymphedema scale. Internal lymphedema was identified through a flexible fiber-optic endoscopic or mirror examination. Patterson's scale was used to grade degrees of internal lymphedema. Results Of the 81 patients, 75.3% (61 of 81) had some form of late-effect lymphedema. Of those, 9.8% (6 of 61) only had external, 39.4% (24 of 61) only had internal, and 50.8% (31 of 61) had both types. Conclusion Lymphedema is a common late effect in patients with head and neck cancer, and it develops in multiple external and internal anatomical locations. During physical examination and endoscopic procedures, clinicians should assess patients with head and neck cancer for late-effect lymphedema. Referral for treatment should be considered when lymphedema is noted. Research is needed to examine risk factors of lymphedema in patients with head and neck cancer and its effects on patients' symptoms, function, and quality of life.