Clinical trial NCT05793749: Early Intervention to Prevent Lower Limb Lymphedema of Gynecological Malignancy
Official title: Early Intervention to Prevent Gynecological Malignant Tumors Clinical Study of Lymphedema of the Lower Limbs in Patients With Radiotherapy After Lymphadenectomy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Uterine Cervical Neoplasms
Endometrial Neoplasms
Lymphedema
Treatment Effectiveness
Keywords: Lymphedema
Endometrial Neoplasms
Uterine Cervical Neoplasms
Treatment Effectiveness
Lead sponsor: Chongqing University Cancer Hospital
Sponsor class: OTHER
First posted: 2023-03-31
Enrollment: 400
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Random grouping (A:B=3:1): A: intervention group; B: nonintervention group
Primary purpose: PREVENTION

Brief summary: This study is a prospective, randomized, controlled clinical trial of a single center in China and plans to enroll 400 patients.

1. Patients with diagnosed gynecological malignancies who underwent pelvic and abdominal lymphadenectomy and required pelvic radiotherapy;
2. Random grouping (A:B=3:1): A. Prophylactic lymphoedema treatment; B. Standard care group;
3. Preventive lymphedema health education was given to patients with gynecological malignant tumors without contraindications before surgery. All patients were randomly divided into an intervention group and a nonintervention group. The intervention group received preventive lymphedema treatment twice a week. 10 times, and the interval between the two treatments was not less than 48 hours and not more than 2 weeks. The intervention measures included four parts: manual lymphatic drainage, skin care, functional exercise, and wearing lymphedema preventive compression stockings. In the nonintervention group, knowledge education and telephone follow-up were routinely conducted.
4. All patients were evaluated for edema, lymphedema symptoms and quality of life 1 day before radiotherapy, every Friday during radiotherapy and every 3 months thereafter. Bioelectrical impedance measurement and leg diameter measurement were used to evaluate edema, the Gynecologic Cancer Lymphedema Questionnaire (GCLQ) was used to evaluate lymphedema symptoms, and the EORTC Quality of Life Scale (QLQ-C30) was used to evaluate quality of life. followed up to 2 years after the end of lymphedema prophylaxis.

Detailed description: Research background Gynecological malignancies, including cervical cancer, ovarian cancer, endometrial cancer, vulvar cancer, etc., are important diseases threatening women's health worldwide, and their main treatment methods are surgery and radiotherapy. During surgery, different numbers of lymph nodes are removed, and lymphatic fluid and tissue exudate from the stump lymphatic vessels accumulate, causing disruption of the original lymphatic circulation and obstruction of lymphatic fluid return, which leads to lower limb edema . The longer the radiotherapy lasts, the more serious the phenomenon of collateral circulation will be, and the lymphatic return pathway will be damaged, resulting in lower limb lymphedema .

Lower extremity lymphedema is a relatively common complication after treatment for gynecologic malignancies, and it has been reported that approximately 20 million patients worldwide are affected by lower extremity lymphedema. The overall incidence of lower extremity lymphedema after gynecologic malignancy treatment is about 25% and can be as high as 70% in special groups . Age, weight, radiotherapy dose, duration of postoperative radiotherapy, tumor stage, daily standing time, number of lymph node dissection, and co-infection are all risk factors for the occurrence of lower extremity lymphedema.

Lymphedema is characterized by sunken edema at the beginning of the disease and progresses to include swelling, numbness, heaviness, tissue fibrosis, impaired movement, and rough epidermal keratinization, and increases the risk of inflammation of the lymphatic vessels and surrounding tissues and cellulitis. Lower extremity lymphedema is a chronic progressive disease that is difficult to cure and has a negative impact on limb function, daily life, quality of life and psychological well-being.

The treatment of lymphedema includes surgical treatment and conservative treatment. The conservative treatment methods include Complex Decongestion Therapy (CDT), external application of Chinese herbal medicine and western medicine, etc. The Complex Decongestion Therapy (CDT) is the most widely used lymphedema treatment with the best efficacy internationally in recent years. The treatment method, but requires long-term or even lifelong care , which brings huge psychological burden and economic pressure to the patient's family. Therefore, lymphedema of the lower extremities should be prevented, and preventive and therapeutic measures should be taken as early as possible to improve the quality of life of patients.

Currently, studies on lymphedema prevention have focused on interventions for breast cancer-related lymphedema , while few studies have been reported on the prevention of lymphedema associated with gynecologic malignancies. Research reported that early intervention with freehand lymphatic drainage technique could effectively prevent lower limb lymphedema, and Research showed that full range of hip exercises could prevent lower limb lymphedema after cervical cancer surgery, in addition, some studies also found that freehand lymphatic drainage combined with Kegel training could prevent vulvar stage I lymphedema after cervical cancer surgery, however, these studies have some limitations, such as small sample size and limited study content. However, these studies have limitations, such as small sample size and limited study content. Moreover, there are no empirical studies on the prevention of lower extremity lymphedema in large samples, and there is no unified standard for the prevention and management of lower extremity lymphedema. Therefore, in this study, the investigators used an evidence-based approach and clinical experience to conduct a prospective study on the prevention of lower limb lymphedema in order to reduce the incidence of lower limb lymphedema, improve patients' quality of life, and reduce their economic burden.

Research objective

1. To understand the incidence of lymphedema after gynecological tumor surgery and radiotherapy and its impact on the quality of life of patients.
2. Through preventive lymphedema treatment intervention, reduce the proportion of lymphedema, reduce the economic burden of patients, and improve their quality of life.
3. We aimed to find a more economical and effective method to treat gynecological malignant tumor lymphedema.

Main outcome measures: The incidence of lower extremity lymphedema after gynecological cancer surgery and radiotherapy, and the incidence of lower extremity lymphedema after prophylactic lymphedema treatment.

Secondary outcome measures: quality of life, incidence of lymphedema symptoms, and progression-free survival (PFS).

Study population

Inclusion criteria:

1. Gynecologic oncology patients undergoing radiotherapy after lymph node surgery who voluntarily participate in this study and sign an informed consent form.
2. 18 to 60 years old.
3. Eastern Cooperative Oncology Group（ECOG) score less than 2.
4. Expected survival time greater than 3 years.
5. Hemoglobin(Hb) greater than or equal to 70 g/L, white blood cells (WBC)greater than or equal to 3.5 × 109 /L, neutrophils(ANC)greater than or equal to 1.5 × 109 /L, platelets (PLT)greater than or equal to 80 × 109 /L.
6. serum alamine aminotransferase(ALT) and glutamic oxalacetic transaminase(AST) less than 2 times the normal value and creatinine less than 1.5 times the normal value, albumin greater than or equal to 35g/L.
7. Women of childbearing potential must have had a pregnancy test (serum or urine) within 7 days prior to enrollment and have a negative result and be willing to use an appropriate method of contraception for the duration of the trial.
8. Ability to comply with the trial protocol, as judged by the investigator.

Exclusion criteria:

1. Lymphedema and deep vein thrombosis of the lower extremities were clearly diagnosed;
2. Acute infection of any kind;
3. Patients with lower extremity edema;
4. pregnancy, menstrual period;
5. Recent major abdominal surgery (determined by the investigator);
6. Radiation colitis, cystitis, intestinal infection, small bowel or large bowel diverticulitis or diverticulitis;
7. Liver fibrosis;
8. Abdominal aortic aneurysm;
9. acute phlebitis;
10. Severe arterial obstructive disease, arterial ulcer, ABPI (ankle-brachial blood pressure index) greater than 1.3 and less than 0.5;
11. Severe peripheral neuropathy;
12. Poor control of hypertension, poor control of stroke and diabetes, and severe bronchial asthma;
13. Patients who cannot understand the experimental content and cannot cooperate and those who refuse to sign the informed consent;
14. Those with concomitant diseases or other special circumstances that seriously endanger the patient's safety or affect the patient's completion of the study.

Subject Termination Criteria

1. The investigator believes that the treatment should be terminated from the perspective of the best benefit of the patients;
2. There are intolerable adverse reactions, after confirmation by the investigator;
3. Failure to complete the treatment according to the cycle and time;
4. The patient withdraws informed consent.

Elimination criteria:

(1) Those who did not meet the standards and were mistakenly included.

Eligibility criteria: Inclusion Criteria:

1.Gynecologic oncology patients undergoing radiotherapy after lymph node surgery who voluntarily participate in this study and sign an informed consent form.

2.18 to 60 years old. 3.Eastern Cooperative Oncology Group（ECOG) score less than 2. 4.Expected survival time greater than 3 years. 5.Hemoglobin(Hb) greater than or equal to 70 g/L, white blood cells (WBC)greater than or equal to 3.5 × 109 /L, neutrophils(ANC)greater than or equal to 1.5 × 109 /L, platelets (PLT)greater than or equal to 80 × 109 /L.

6.serum alamine aminotransferase(ALT) and glutamic oxalacetic transaminase(AST) less than 2 times the normal value and creatinine less than 1.5 times the normal value, albumin greater than or equal to 35g/L.

7.Women of childbearing potential must have had a pregnancy test (serum or urine) within 7 days prior to enrollment and have a negative result and be willing to use an appropriate method of contraception for the duration of the trial.

8.Ability to comply with the trial protocol, as judged by the investigator.

Exclusion Criteria:

1. Lymphedema and deep vein thrombosis of the lower extremities were clearly diagnosed;
2. Acute infection of any kind;
3. Patients with lower extremity edema;
4. pregnancy, menstrual period;
5. Recent major abdominal surgery (determined by the investigator);
6. Radiation colitis, cystitis, intestinal infection, small bowel or large bowel diverticulitis or diverticulitis;
7. Liver fibrosis;
8. Abdominal aortic aneurysm;
9. acute phlebitis;
10. Severe arterial obstructive disease, arterial ulcer, ABPI (ankle-brachial blood pressure index) greater than 1.3 and less than 0.5;
11. Severe peripheral neuropathy;
12. Poor control of hypertension, poor control of stroke and diabetes, and severe bronchial asthma;
13. Patients who cannot understand the experimental content and cannot cooperate and those who refuse to sign the informed consent;
14. Those with concomitant diseases or other special circumstances that seriously endanger the patient's safety or affect the patient's completion of the study.

Primary outcomes:
measure: Incidence of lymphedema
timeFrame: Incidence of lymphedema in the prophylactic lymphedema treatment group and the standard treatment group at 2 years after the end of radiotherapy
measure: Quality of life of patients
timeFrame: Quality of life QLQ-C30 scores for the prophylactic lymphedema treatment group and the standard treatment group at 2 years after the end of radiotherapy
Secondary outcomes:
measure: Subjective feelings
timeFrame: Quality of life GCLQ scores for the prophylactic lymphedema treatment group and the standard treatment group at 2 years after the end of radiotherapy
measure: 2-year progression-free survival,2-year PFS
timeFrame: 2-year PFS was defined as the time from randomization to the first occurrence of disease progression or death from any cause within 2 years
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
Study officials:
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