Surgery vs Conservative Therapy for Breast Cancer-Related Lymphedema

(LYMPH Trial)

Recruiting at 46 trial locations

Overseen By Elisabeth Kappos, Prof. Dr.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Hospital, Basel, Switzerland

Disqualifiers: Primary lymphedema, Non-BCRL, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 1 year

280 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether surgery can improve the quality of life for individuals with lymphedema, a condition where arms swell due to lymph fluid build-up after breast cancer. It compares surgery with a non-surgical treatment called Conservative Complex Physical Decongestion Therapy, which includes massage, exercises, and compression garments. Suitable participants have had breast cancer, experienced lymphedema for over three months, and have already tried physical therapy. The goal is to determine if surgery more effectively improves daily life and reduces symptoms. As an unphased trial, this study provides patients the chance to explore innovative treatment options that could enhance their quality of life.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that these treatments for breast cancer-related lymphedema are safe?

Research has shown that surgical treatments like Lymphovenous Anastomosis (LVA) and Vascularized Lymph Node Transfer (VLNT) are generally safe for individuals with breast cancer-related lymphedema. Studies indicate these surgeries carry a low risk of complications and are well-tolerated. Specifically, one study found that LVA is safe and helps protect against complications.

For non-surgical treatment, Complex Physical Decongestion Therapy (CDT) is commonly used and serves as a standard method for managing lymphedema. This therapy includes skincare, manual lymphatic drainage (a special type of massage), exercises, and wearing compression garments. It is typically well-tolerated as part of regular care.

Overall, both surgical and non-surgical treatments have proven to be safe options for managing lymphedema. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores two very different approaches to managing breast cancer-related lymphedema. Unlike standard care, which often involves lymphatic drainage and compression therapy, this trial considers the potential of surgical intervention. The surgical approach offers flexibility, allowing surgeons to tailor the procedure, including lymphovenous anastomosis and lymph node harvesting, to the patient's needs. Meanwhile, the conservative therapy arm emphasizes a structured, two-phase management plan combining manual lymphatic drainage, exercise, and compression garments. This trial could reveal valuable insights into which method offers more effective relief and long-term benefits for patients suffering from lymphedema.

What evidence suggests that this trial's treatments could be effective for breast cancer-related lymphedema?

This trial will compare Surgical Intervention, including procedures like lymphovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT), with Conservative Complex Physical Decongestion Therapy (CDT) for breast cancer-related lymphedema. Research has shown that certain surgeries can help people with long-term lymphedema by improving lymph fluid flow, reducing swelling, and easing movement of the affected limb. Studies have found that the benefits of these surgeries last over time.

In contrast, CDT is a common non-surgical treatment. It includes methods like manual lymphatic drainage, a special type of massage, and wearing compression garments to manage symptoms. Both surgery and CDT aim to reduce swelling and enhance quality of life, but surgery may offer more lasting relief by addressing the underlying issue. Participants in this trial will join either the surgical group or the CDT group to evaluate the effectiveness of these treatments. ^{1 2 3 5 6}

Who Is on the Research Team?

Elisabeth Kappos, Prof. Dr.

Principal Investigator

University Hospital, Basel, Switzerland

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've had breast cancer treatment (like lymph node removal or radiotherapy) and now have chronic swelling in their arms, known as lymphedema. They should have tried decongestion therapy for at least 3 months and be able to fill out quality of life surveys.

Inclusion Criteria

Written informed consent

I have had swelling in one limb for more than 3 months, and it's significantly larger than the other.

Minimum of 3 months CDT

Exclusion Criteria

My surgeon decided I don't need surgery for my lymph nodes.

My lymphedema is either present from birth or not caused by breast cancer.

I need urgent surgery for my lymphedema as advised by a specialist.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either lymphatic surgery or conservative complex physical decongestion therapy (CDT) for chronic breast cancer-associated lymphedema

Approximately 1 year

Follow-up

Participants are monitored for safety, effectiveness, and quality of life improvements after treatment

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Conservative Complex Physical Decongestion Therapy
• Surgical Intervention

Trial Overview The LYMPH Trial is comparing two ways to treat arm swelling after breast cancer: standard physical therapy versus surgery. The goal is to see which method improves patients' quality of life better one year after the treatment.

How Is the Trial Designed?

Group I: Group A : Surgical Group Experimental Treatment 1 Intervention

According to the pragmatic study design, neither the diagnostic workup nor the surgery will be standardized in order to offer surgeons considerable leeway on how to perform lymphatic surgery, which resembles the flexibility in usual care. The key aspects of the preoperative workup and the surgery including the number of LVAs (Lymphovenous Anastomosis), harvesting of lymph nodes ("donor site"), time of surgery, and practical details will be registered.

Group II: Group B: Conservative Complex Physical Decongestion Therapy (control group) Active Control 1 Intervention

CDT (Conservative Complex Physical Decongestion Therapy) will be performed as in usual care, following the pragmatic study design. The key aspects like frequency of lymphatic drainage, time when lymphatic drainage is performed and time and class of compressive garments are used will be documented. CDT incorporates two stages of treatment. The first treatment phase (intensive phase) entails skincare, MLD (manual lymphatic drainage), exercises aimed at improvement of mobility/range of motion in the shoulder, elbow or wrist joints, and compression therapy through bandaging. Most patients undergo this phase shortly after the diagnosis of LE. CDT in the second phase (maintenance phase) aims to maintain the achieved limb volume/ circumference reduction through compression with therapeutic elastic compression garment for the arm. Skincare, mobility exercises and MLD is continued in this phase if needed

Conservative Complex Physical Decongestion Therapy is already approved in European Union, United States, Canada, Switzerland for the following indications:

Approved in European Union as Complex Physical Decongestive Therapy for:

• Chronic breast cancer-related lymphedema

Approved in United States as Complex Physical Decongestive Therapy for:

• Chronic breast cancer-related lymphedema

Approved in Canada as Complex Physical Decongestive Therapy for:

• Chronic breast cancer-related lymphedema

Approved in Switzerland as Complex Physical Decongestive Therapy for:

• Chronic breast cancer-related lymphedema

Who Is Running the Clinical Trial?

University Hospital, Basel, Switzerland

Lead Sponsor

Trials

1,031

Recruited

2,503,000+

Swiss National Science Foundation

Collaborator

Trials

227

Recruited

457,000+

Rising Tide Foundation

Collaborator

Trials

17

Recruited

6,200+

Krebsforschung Schweiz, Bern, Switzerland

Collaborator

Trials

21

Recruited

15,300+

Published Research Related to This Trial

In a study of 115 patients receiving a 7 Gy HDR-brachytherapy boost after conservative breast cancer treatment, the cosmetic outcomes were rated as satisfactory by 96% of patients and 85% of physicians, indicating good aesthetic results despite some reported side effects.

Late toxicity was observed in the form of breast pain (39%), fibrosis (75%), and telangiectasias (56%), but overall, the HDR-brachytherapy boost was associated with acceptable levels of toxicity, suggesting it is a viable option for enhancing breast preservation in patients with local relapse risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conservative surgery, external radiotherapy, and HDR brachytherapy in a single fraction of 7 Gy in early breast cancer: long-term toxicity and esthetic assessment. Rodríguez Pérez, A., López Carrizosa, MC., Samper Ots, PM., et al.[2021]

Conservative treatment for breast cancer, which includes surgical excision followed by local radiotherapy, has been shown to provide good functional and cosmetic outcomes for patients, as evidenced by over 1100 cases treated since 1977.

The study identified specific criteria that contribute to effective local tumor control and positive results, highlighting the importance of careful patient selection and management in conservative breast cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Local treatment of breast carcinoma: when is breast-saving therapy not indicated?]. Dupont Lampert, V., Zuber, M., Laffer, U., et al.[2017]

In a review of 164 patients who underwent conservative breast cancer treatment, factors such as the tumor's location in the lower external quadrant and the type of adjuvant therapy significantly influenced cosmetic outcomes after surgery and radiotherapy.

The study found that certain combined treatments, like CMF and anthracycline plus Tamoxifen, may negatively impact cosmetic results, highlighting the need for personalized treatment plans that consider both the cancer characteristics and the patient's preferences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Esthetic results of the conservative treatment in breast carcinoma]. Moro, G.[2013]

The combination of radiation therapy and conservation surgery for Stage I and II breast cancer patients provides similar overall survival and recurrence-free survival rates as radical mastectomy, while also allowing for breast preservation, which can have psychological benefits.

Current studies suggest that adding chemotherapy to conservation surgery and radiation therapy may lead to increased complications and poorer cosmetic outcomes, but it does not affect survival, prompting further investigation into the appropriate use and timing of chemotherapy in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary treatment of early breast cancer with conservation surgery and radiation therapy. The effect of adjuvant chemotherapy. Levitt, SH.[2019]

Radiotherapy can be an effective alternative to surgery for breast cancer treatment, especially in cases where surgery is not possible or when it can provide similar outcomes in terms of cancer control and aesthetic results, particularly for larger tumors (T > 3 cm).

Recent studies indicate that the type of treatment (conservative vs. radical) does not significantly affect survival rates, and advancements in radiotherapy have improved its tolerability, allowing for lower doses and making it a viable option for patients who may eventually require surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Radiotherapy--an alternative to surgery in the treatment of breast cancer]. Baillet, F.[2006]

Conservative surgery combined with radiotherapy is effective for local control of early breast cancer and maintains good cosmetic outcomes, as supported by retrospective studies.

Long-term survival rates at five and ten years show that this approach is comparable to mastectomy, suggesting that significant survival differences between the two methods are unlikely to emerge with further follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of conservative surgery and radiotherapy as primary local treatment for early carcinoma of the breast. Harris, JR., Recht, A., Schnitt, S., et al.[2019]

In a study of 150 patients undergoing oncoplastic breast surgery, the use of closed incision negative pressure therapy (ciNPT) significantly reduced postoperative wound healing complications, with a complication rate of 10.3% compared to 31% in the standard of care group.

Patients treated with ciNPT experienced no delays in starting adjuvant therapy, while 22.5% of those receiving standard care faced delays, highlighting ciNPT's potential to improve recovery and treatment timelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Closed Incision Negative Pressure Therapy in Oncoplastic Surgery Prevents Delays to Adjuvant Therapy. Ockerman, KM., Bryan, J., Wiesemann, G., et al.[2023]

Breast conservation therapy (BCT) is now a standard treatment for early-stage breast cancer, providing similar local control and survival rates as mastectomy, especially when combined with radiation therapy after surgery.

The American College of Radiology's expert panel established updated guidelines for BCT, addressing various clinical scenarios and factors such as patient age, tumor characteristics, and radiation methods to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

American College of Radiology appropriateness criteria on conservative surgery and radiation: stages I and II breast carcinoma. White, JR., Halberg, FE., Rabinovitch, R., et al.[2008]

Citations

1. journals.lww.com journals.lww.com/plasreconsurg/abstract/9900/outcomes_of_lymphovenous_anastomoses_and.2714.aspx

Plastic and Reconstructive Surgery Outcomes of Lymphovenous Anastomoses and Vascularized Lymph Node Transplant in the Combined Surgical Treatment of Lymphedema: A Prospective ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11930869/

Vascularized lymph node transfer (VLNT) versus ... In contrast, microsurgical interventions have efficiently shown promising long-term outcomes by tackling the underlying pathophysiology of chronic BCRL [10–12].

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39653884/

Vascularized lymph node transfer (VLNT) versus ... VLNT and LVA are both effective in long-term lymphedema management, yet they demonstrate marked differences in the timing of improvement.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1748681525002852

Immediate lymphovenous anastomosis is effective in ... This study showed that ILA has a protective effect on BCRL rates in patients undergoing ALND. ILA has also been shown to be a safe procedure with low risk of ...

5. medrxiv.org medrxiv.org/content/10.1101/2024.02.13.24302744v1.full-text

The LYMPH Trial - Comparing Microsurgical with ... Lymphovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT) are microsurgical techniques that aim to restore lymphatic drainage.

6. gs.amegroups.org gs.amegroups.org/article/view/120239/html

Surgical treatment of breast cancer related lymphedema—the ... This study aims to review the combined approach for breast cancer-related lymphedema treatment and propose a new therapeutic algorithm based on recent ...