Prevention of Postoperative Complications by Negative Pressure Therapy After Complex Breast Cancer Surgery

Breast Cancer Clinical Trial

— TPN-SEIN  

Official title:

Prevention of Postoperative Complications by Negative Pressure Therapy After Complex Breast Cancer Surgery: a Prospective Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06265558
• Other study ID #: PROICM 2023-08 TPN
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 2024
• Est. completion date: February 2027

Study information

• Verified date: June 2024
• Source: Institut du Cancer de Montpellier - Val d'Aurelle
• Contact: Mathias NERON, MD
• Phone: 467614813
• Email: mathias.neron[@]icm.unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

There is little scientific data concerning the use of negative pressure therapy after immediate breast reconstruction.

That strategy of treatment-reconstruction has expanded increasingly since the last years.

The current literature reports only 3 studies on the use of preventive negative pressure therapy in oncologic breast surgery.

Moreover, all three are retrospective, case-control studies with serious limitations.

The largest published series reports a reduction in the overall complication rate from 15.9% to 8.5%, and a significant reduction in several criteria: infection, scar dehiscence and necrosis. However, the study presents significant biases, with non-comparable populations in terms of comorbidities, surgical procedure performed, inclusion periods (and therefore experience in performing oncological surgery).

There was also a high probability of under-assessment or postponement of post-operative complications, which is typical of published retrospective surgical studies.

The published results therefore strongly encourage further investigation of negative pressure therapy in oncological breast surgery.

Description:

In 2022, excisional surgery is still one of the mainstays of breast cancer treatment. The excisional surgery is often combined with adjuvant treatments, which may include medical treatments such as chemotherapy, targeted therapies and immunotherapy, hormone therapy and radiotherapy. All these treatments have toxicities that impact on patients' quality of life.

One of the main complications of surgery is scarring. The rate is around 2% for "simple" breast surgery (conservative breast surgery - total mastectomy). This rate can rise sharply in the case of "complex" breast surgery, such as high-level oncoplasty, or mastectomy with Immediate Breast Reconstruction (IBR). This rate of surgical wound complications (ischemia, necrosis, dehiscence, infection) reached 20% in our local series of Immediate Breast Reconstruction (IBR) by prosthesis. This rate may exceed 30% in some series, depending on the surgical technique and the population, in cases of smoking, diabetes, previous radiotherapy, obesity and large breast volume. The increasing prevalence of these risk factors in the population means that scarring disorders must be taken into account in daily cancer care.

The impact of these scarring disorders is manifold:

• Delayed initiation of adjuvant therapy with an impact on overall survival.

• Cosmetic impact of scarring

• Possible loss of prosthetic breast reconstruction

• Patient dissatisfaction, with increased burden of care

• Overall impact on patient quality of life

• Economic impact linked to the length of care over time (consumption of dressing materials and personal time) Preventing the onset of wound-healing disorders is therefore vital in order to avoid these multiple consequences for the patient and the healthcare system.

In breast surgery, the use of preventive NPT (Negative Pressure Therapy) has been little studied. The NPT has been used mainly in cosmetic surgery procedures such as breast reduction, with results in favor of NPT. The most comprehensive study is a multicenter randomized trial which included 200 patients scheduled for bilateral breast reduction. In this trial, the comparison was made between the 2 breasts, each patient being her own control. The calculation of the number of subjects was based on a reduction in the complication rate from 20% to 10% (i.e., a 50% reduction). The study was positive, showing a reduction in the dehiscence rate at day 21 from 26% to 16%. In this study, patients were under-selected, and around 40% had risk factors for complications. A second randomized study, with similar methodology and judgment criteria, included 32 patients undergoing bilateral breast reduction. The results of this study are significant, but unfortunately there weren't much detail in the publication.

There is little scientific data concerning the use of negative pressure therapy after immediate breast reconstruction. There are very few data on the use of Negative pressure Therapy (NPT) after immediate Breast Reconstruction (IBR), a treatment-reconstruction strategy that has been expanding rapidly since recent years. The current literature reports only 3 studies on the use of preventive Negative pressure Therapy (NPT) in oncologic breast surgery. All three are retrospective, case-control studies with serious limitations. The largest published series involved 356 patients and 665 breasts. A reduction was reported in the overall complication rate from 15.9% to 8.5%, and a significant reduction in several criteria: infection, seroma, scar dehiscence and necrosis. However, the study presents significant biases, with non-comparable populations in terms of co-morbidities, surgical procedure performed, inclusion periods (and therefore experience in performing oncological surgery). There was also a high probability of under-assessment or postponement of post-operative complications, which is typical of published retrospective surgical studies.

The published results therefore strongly encourage further investigation of Negative Pressure Therapy (NPT) in oncological breast surgery.

Our hypothesis, then, is that preventive NPT in the immediate post-operative phase of complex breast surgery can prevent the onset of post-operative scarring disorders and shorten the time to complete healing.

To date, there are no randomized prospective studies of NPT in complex oncologic breast surgery. Randomized studies already published in general surgery provide a good level of evidence for the efficacy of NPT in preventing local post-operative complications. The latest systematic review and meta-analysis found a reduction in the risk of surgical site infection, from 13% to 8.8%, all types of surgery included. The benefit on the risk of dehiscence in general surgery is less strong, but a 30% reduction was found in a meta-analysis of studies involving only a preventive NPT device, a device widely used throughout the world.

In view of these results from randomized trials in general surgery and non-oncological breast surgery, and the results of retrospective studies in oncological breast surgery, a randomized trial must be carried out. This randomized controlled trial will be pragmatic, incorporating an intermediate analysis, given the endpoint evaluating the reduction in complications in a surgical context, to rapidly meet our objectives with a sufficient level of evidence to have an immediate impact on patients and modify practice.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 254
• Est. completion date: February 2027
• Est. primary completion date: February 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Female = 18 years

2. Patient with unilateral invasive or in situ breast carcinoma

3. Patient with or without neoadjuvant treatment

4. Patient presenting an indication for complex breast surgery by mastectomy with immediate breast reconstruction by implant or oncoplasty by T-shaped mammoplasty.

5. Patient presenting at least one of the following risk factors for scarring disorders:

• Obesity with Body Mass Index BMI = 30

• Cup size = E

• Active smoking or smoking cessation for less than one month

• Diabetes

• History of homolateral breast radiotherapy

• Long-term corticosteroid therapy

6. Patient to have signed informed consent prior to study entry

7. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

8. Patient affiliated with a health insurance plan.

Exclusion Criteria:

1. Legal incapacity or limited legal capacity. Medical or psychological conditions preventing the patient from completing the study or signing the consent form.

2. Pregnant or breast-feeding patient

3. Patient under guardianship or safeguard of justice

4. Patient participating in an interventional study with the objective of wound healing

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Postoperative Complications

Intervention

Procedure:
• Negative pressure therapy (NPT)
Negative pressure therapy (NPT) involves placing the surface of a wound under a pressure lower than the ambient atmospheric pressure. To achieve this, a specially designed dressing is connected to a vacuum source and an exudate collection system.
• Dressing
Fatty dressing or hydrocolloid dressing

Locations

Country	Name	City	State
France	Centre Hospitalier de Montpellier	Montpellier	Hérault
France	Institut régional du Cancer de Montpellier	Montpellier	Hérault
France	Centre Hospitalier de Nîmes	Nîmes	Gard

Sponsors (1)

Lead Sponsor	Collaborator
Institut du Cancer de Montpellier - Val d'Aurelle

Country where clinical trial is conducted

France, 

References & Publications (13)

Bleicher RJ, Moran MS, Ruth K, Edge SB, Dietz JM, Wilke LG, Stearns V, Kurtzman SH, Klein J, Yao KA. The Impact of Radiotherapy Delay in Breast Conservation Patients Not Receiving Chemotherapy and the Rationale for Dichotomizing the Radiation Oncology Time-Dependent Standard into Two Quality Measures. Ann Surg Oncol. 2022 Jan;29(1):469-481. doi: 10.1245/s10434-021-10512-1. Epub 2021 Jul 29. — View Citation

Bowen ME, Mone MC, Buys SS, Sheng X, Nelson EW. Surgical Outcomes for Mastectomy Patients Receiving Neoadjuvant Chemotherapy: A Propensity-Matched Analysis. Ann Surg. 2017 Mar;265(3):448-456. doi: 10.1097/SLA.0000000000001804. — View Citation

Cagney D, Simmons L, O'Leary DP, Corrigan M, Kelly L, O'Sullivan MJ, Liew A, Redmond HP. The Efficacy of Prophylactic Negative Pressure Wound Therapy for Closed Incisions in Breast Surgery: A Systematic Review and Meta-Analysis. World J Surg. 2020 May;44(5):1526-1537. doi: 10.1007/s00268-019-05335-x. — View Citation

Chicco M, Huang TC, Cheng HT. Negative-Pressure Wound Therapy in the Prevention and Management of Complications From Prosthetic Breast Reconstruction: A Systematic Review and Meta-analysis. Ann Plast Surg. 2021 Oct 1;87(4):478-483. doi: 10.1097/SAP.0000000000002722. — View Citation

Clough KB, Kaufman GJ, Nos C, Buccimazza I, Sarfati IM. Improving breast cancer surgery: a classification and quadrant per quadrant atlas for oncoplastic surgery. Ann Surg Oncol. 2010 May;17(5):1375-91. doi: 10.1245/s10434-009-0792-y. Epub 2010 Feb 6. — View Citation

Donovan CA, Harit AP, Chung A, Bao J, Giuliano AE, Amersi F. Oncological and Surgical Outcomes After Nipple-Sparing Mastectomy: Do Incisions Matter? Ann Surg Oncol. 2016 Oct;23(10):3226-31. doi: 10.1245/s10434-016-5323-z. Epub 2016 Jun 28. — View Citation

Gabriel A, Sigalove S, Sigalove N, Storm-Dickerson T, Rice J, Maxwell P, Griffin L. The Impact of Closed Incision Negative Pressure Therapy on Postoperative Breast Reconstruction Outcomes. Plast Reconstr Surg Glob Open. 2018 Aug 7;6(8):e1880. doi: 10.1097/GOX.0000000000001880. eCollection 2018 Aug. — View Citation

Gagliato Dde M, Gonzalez-Angulo AM, Lei X, Theriault RL, Giordano SH, Valero V, Hortobagyi GN, Chavez-Macgregor M. Clinical impact of delaying initiation of adjuvant chemotherapy in patients with breast cancer. J Clin Oncol. 2014 Mar 10;32(8):735-44. doi: 10.1200/JCO.2013.49.7693. Epub 2014 Jan 27. — View Citation

Galiano RD, Hudson D, Shin J, van der Hulst R, Tanaydin V, Djohan R, Duteille F, Cockwill J, Megginson S, Huddleston E. Incisional Negative Pressure Wound Therapy for Prevention of Wound Healing Complications Following Reduction Mammaplasty. Plast Reconstr Surg Glob Open. 2018 Jan 12;6(1):e1560. doi: 10.1097/GOX.0000000000001560. eCollection 2018 Jan. Erratum In: Plast Reconstr Surg Glob Open. 2018 Mar 23;6(2):e1720. — View Citation

Johnson ON 3rd, Reitz CL, Thai K. Closed Incisional Negative Pressure Therapy Significantly Reduces Early Wound Dehiscence after Reduction Mammaplasty. Plast Reconstr Surg Glob Open. 2021 Mar 22;9(3):e3496. doi: 10.1097/GOX.0000000000003496. eCollection 2021 Mar. — View Citation

Norman G, Goh EL, Dumville JC, Shi C, Liu Z, Chiverton L, Stankiewicz M, Reid A. Negative pressure wound therapy for surgical wounds healing by primary closure. Cochrane Database Syst Rev. 2020 Jun 15;6(6):CD009261. doi: 10.1002/14651858.CD009261.pub6. — View Citation

Saunders C, Nherera LM, Horner A, Trueman P. Single-use negative-pressure wound therapy versus conventional dressings for closed surgical incisions: systematic literature review and meta-analysis. BJS Open. 2021 Jan 8;5(1):zraa003. doi: 10.1093/bjsopen/zraa003. — View Citation

Tanaydin V, Beugels J, Andriessen A, Sawor JH, van der Hulst RRWJ. Randomized Controlled Study Comparing Disposable Negative-Pressure Wound Therapy with Standard Care in Bilateral Breast Reduction Mammoplasty Evaluating Surgical Site Complications and Scar Quality. Aesthetic Plast Surg. 2018 Aug;42(4):927-935. doi: 10.1007/s00266-018-1095-0. Epub 2018 Feb 13. Erratum In: Aesthetic Plast Surg. 2018 Apr 2;: — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of patients with post-operative scarring trouble	Number of patients with post-operative scarring trouble divided by the total number of patients operated on in the trial.	From baseline to 30 days after surgery
Secondary	Rate of patients with a surgical site infection	Number of patients with surgical site infection divided by total number of patients operated on in the trial.	From baseline to 90 days after the surgery
Secondary	Surgical revision rate	Number of patients with repeat surgery divided by the total number of patients operated on in the trial.	From baseline to 90 days after the surgery
Secondary	Rate of patients with at least one rehospitalization	Number of patients with at least one rehospitalization divided by total number of patients operated on in the trial.	Frm baseline to 90 days after the surgery
Secondary	Surgical complication rate by Clavien-Dindo classification	The Clavien-Dindo classification of surgical classifications is used throughout surgery for grading adverse events (complications) which occur as a result of surgical procedures. It includes 5 grades from grade 1 (recourse to usual postoperative treatments) to Grade 5 (death).	Approximately 10 days, from surgery to hospital discharge
Secondary	Time to initiation of adjuvant therapy	Number of days between surgery and initiation of adjuvant therapy	Approximately 3 months, from surgery to beginning of adjuvant therapy
Secondary	Quality of life evaluated by questionnaire QLQ-C30 (Version 3)	The EORTC QLG Core Questionnaire (EORTC QLQ-C30) is a 30-item instrument designed to measure quality of life in all cancer patients.Version 3, incorporates five functional scales on physical (PF), role (RF), cognitive (CF), emotional (EF) and social (SF) functioning, three symptom scales on fatigue (FA), pain (PA) and nausea and vomiting (NV), single items assessing dyspnoea (DY), insomnia (SL), loss of appetite (AP), constipation (CO) and diarrhoea (DI), one item assessing perceived financial impact (FI) and a global health status/QoL scale (Global QoL). Each item is scored in one of four categories 1) 'Not at all', 2) 'A little', 3) 'Quite a bit' 4) 'Very much', with the exception of 'Global QoL'which ranges from 1) 'Very poor' to 7) 'Excellent'.; Scoring of the items in the PF scale in the latest revision of EORTC QLQ-C30, Version 3 is extended to the four-point scale instead of the previous 'Yes/No' dichotomy	From baseline to 15 days then to 30 and 90 days after surgery
Secondary	Quality of life evaluated by questionnaire QLQ-BReast cancer (BR23)	The Breast Cancer module is a supplementary questionnaire module to be employed in conjunction with the QLQ-C30. The QLQ-BR23 incorporates five multi-item scales to assess body image, sexual functioning, systemic therapy side effects, breast symptoms, and arm symptoms. All of the scales and single-item measures range in score from 0 to 100. A high score for the functional scales represents a high/healthy level of functioning, whilst a high score for the symptom scales represents a high level of symptomatology or problems.	From baseline to 15 days then to 30 and 90 days after surgery
Secondary	Patient satisfaction about cosmetic result evaluated using the BR23 questionnaire	The QLQ-BR23 incorporates five multi-item scales to assess body image, sexual functioning, systemic therapy side effects, breast symptoms, and arm symptoms.	From baseline to 15 days then to 30 and 90 days after surgery
Secondary	Medical cost of post-surgery care	There will be a comparison between two arms. The medical cost of post-surgery care will be calculated on the basis of data such as number and type of dressings, consumables, time spent by the nurse, reason for hospital consultations and hospitalization, type of transport with home-hospital distance.	From baseline to 90 days after surgery

External Links

•   Breast cancers - Recommendations and practice aids
•   French Society of Senology and Breast Pathology multimedia library