Primary Radiotherapy And DIEP flAp reconstruction (PRADA) study

• Research type

  Research Study

• Full title

  Neoadjuvant Chemotherapy and Radiotherapy before Mastectomy & DIEP Reconstruction

• IRAS ID

  154616

• Contact name

  Fiona MacNeill

• Contact email

  fiona.macneill@rmh.nhs.uk

• Sponsor organisation

  The Royal Marsden Hospital

• Duration of Study in the UK

  2 years, 5 months, 1 days

• Research summary

  Research Summary

  To find out the surgical safety of performing complex surgery (breast removal and breast reconstruction using transplanted abdominal fat) after breast/chest wall/armpit/lower neck radiotherapy (RT).

  Women with breast cancer are often cured or can live for a long time. In view of this modern breast cancer surgery aims to leave as natural a breast shape as possible. Keeping a natural breast appearance has been shown to be very important to a woman’s emotional and psychological recovery.

  Breast cancer is often treated with a combination of surgery, chemotherapy, radiotherapy (type of x-ray), anticancer tablets (eg Tamoxifen) and newer targeted drugs (eg Herceptin). Traditionally surgery was the first treatment but world-wide cancer doctors are successfully changing the order in which treatments are given.

  Radiotherapy is usually given after surgery: however radiotherapy after mastectomy and breast reconstruction can damage the ‘new’ breast giving a less good breast shape and appearance in the longer term. Also, if recovery is prolonged following complex reconstructive surgery, the radiotherapy is delayed which may reduce effectiveness.

  Changing the order of treatments has been shown to be safe and effective for chemotherapy, Herceptin and anticancer tablets but we have very little information on giving radiotherapy before breast cancer surgery.

  Firstly we want to find out if giving radiotherapy before mastectomy and reconstruction alters the surgery complication rates. We will also be assessing the 'quality' of the reconstructed breast by asking the patients a short questionnaire, by using a 3-dimensional camera and by quantifying the stiffness of the breast tissue.

  If surgery after RT can be done safely we can then plan future, more detailed research studies comparing the appearance of the breast when radiotherapy is given before or after reconstruction as well as comparing overall time taken to complete anti-cancer treatments.

  Summary of Results

  Background:
  Radiotherapy after mastectomy (adjuvant) has been shown to have both a local and survival benefit, particularly in high-risk women. However, if the mastectomy is carried out with simultaneous immediate reconstruction using spare lower abdominal tissue (DIEP reconstruction), adjuvant radiotherapy also affects the healthy tissue transplanted from the abdomen and this can result in less good cosmetic outcomes. PRADA offers radiotherapy before mastectomy and reconstruction so sparing the abdominal tissue breast reconstruction.

  There are precedents for the use of upfront (neoadjuvant) radiotherapy (NART) followed by complex cancer surgery. For example, in rectal cancer, there is substantial evidence for the use of neoadjuvant chemotherapy and radiotherapy followed by aggressive surgical excision as the standard of care in patients with a threatened or involved circumferential margin. Short-course preoperative radiotherapy has been tested in multiple trials in rectal cancer, including the Swedish Rectal Cancer Trial, Dutch Colorectal Cancer Group Study and more recently the Medical Research Council CR07 trial. All three studies demonstrated better local control and improved disease-free and overall survival. Flap reconstruction of the perineum at the time of abdomino-perineal resection is well described as a method to reduce perineal morbidity and is indicated when primary closure cannot be achieved after wide local resection. By transferring a bulk of vascularized soft tissue into the irradiated pelvis, flap reconstruction has been shown to reduce infection rates, fill pelvic dead space, prevent wound dehiscence, and reduce time to healing. ‘Short course’ pre-operative rectal radiotherapy: surgery is generally undertaken 7-10 days after completion of radiotherapy with an acceptable impact on post-operative complication rate.

  There is one published series of NART in breast cancer reporting an acceptable post-operative complication rate. Following on from this, surgeons and radiation oncologists from the Royal Marsden and Imperial College developed experience of conducting mastectomy and DIEP reconstruction 2-6 weeks following completion of radiotherapy (10 cases, no significant post-operative complications). PRADA is a non­randomised phase I study to formally evaluate the safety of reversing the order of mastectomy plus immediate DIEP flap reconstruction and adjuvant radiotherapy, with a view to a subsequent randomised controlled trial testing local control and cosmetic outcomes.

  Objectives:
  Radiotherapy (RT) prior to mastectomy with immediate DIEP flap reconstruction:
  • Is feasible with equivalent acute complications rates to standard mastectomy and immediate DIEP flap reconstruction performed prior to RT
  • Will improve the long-term aesthetic outcome of mastectomy and immediate DIEP flap reconstruction in patients requiring radiotherapy
  • Avoids delays to radiotherapy after surgery because of wound healing issues.
  • Will ultimately increase immediate reconstruction rates
  • Will expedite the duration of the overall patient pathway
  • Sequential chemo-radiotherapy will result in greater oncological outcomes

  Main findings:
  Preoperative radiotherapy followed by skin-sparing mastectomy and DIEP flap reconstruction is technically feasible, with low rates of surgical complications and good short-term oncological outcomes.

  Implications for practice/future research:
  Further evaluation in a randomised trial of preoperative radiotherapy versus conventional post-mastectomy radiotherapy in breast reconstruction is now required to compare oncological and quality-of-life outcomes.

• REC name

  London - Camden & Kings Cross Research Ethics Committee

• REC reference

  15/LO/1071

• Date of REC Opinion

  7 Jul 2015

• REC opinion

  Favourable Opinion