Feasibility Study of Accelerated Preoperative Radiotherapy for Early Breast Cancer

The standard treatment for women with a relatively small breast cancer without arguments for involvement of the axillary lymph nodes, is breast conserving surgery followed by radiotherapy of the whole breast, often with a complementary dose to the operated area (boost). A delay of 3-4 weeks after surgery is advisable for allowing wound healing before the start of radiotherapy. Historically, whole breast radiotherapy plus boost are delivered in 6-7 weeks. This treatment can be associated with temporary fatigue and decrease in quality of life. Randomized trials have shown that shorter schedules, delivering slightly more dose per day during 3 weeks, are equal to the long schedules. In an earlier clinical study, the investigators have tested such a short schedule and shown that it is equally safe and equally well tolerated as the conventional schemes. Other hospitals have examined (and still are examining) the safety and tolerance of even shorter schedules, delivering radiotherapy in 1 week.

This clinical study involves delivering radiotherapy in 1 week and before the surgery in stead of following surgery. In the postoperative setting, it is often debatable which volume should be included in the boost. Often boost-volumes remain large because of uncertainties in delineation. Preoperative radiotherapy has the advantage that the tumor is visible on imaging. This can result in smaller boost volumes. The surgery will follow shortly after termination of the radiotherapy, resulting in a very short treatment period.

This study is an open study investigating the effect on quality of life of a very short preoperative radiotherapy for early breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Tomotherapy

Detailed Description

Women with early breast cancer are treated with breast conserving surgery (BCS) followed by whole breast irradiation (WBI) and a complementary dose to the lumpectomy cavity (boost). A delay of 3-4 weeks after surgery is advisable for allowing wound healing before the start of radiotherapy. Historically, WBI plus boost are delivered in 6-7 weeks. This treatment is associated with fatigue and a decreased quality of life. Randomized trials have shown that shorter hypofractionated schedules, delivering radiotherapy in 3 weeks, are equal to the long schedules. The investigators have shown that a hypofractionated tomotherapy with a simultaneous integrated boost is oncologically safe, well tolerated and has less impact on quality of life than the conventional schemes.

In the postoperative setting, it is often debatable which volume should be included in the boost. Surgical clips can help to decrease inter-observer variability, but often boost-volumes remain large because of uncertainties in delineation. Preoperative radiotherapy has the advantage that the gross tumor volume (GTV) is visible on imaging. This can result in smaller boost volumes.

The aim of this study is to investigate the feasibility of a short preoperative tomotherapy. The potential benefits are

• a decrease in overall treatment time
• a positive effect on quality of life
• a more precise target delineation
• profitable health economics.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1020
    • CHU Brugmann
  • Brussels, Belgium, 1090
    • UZ Brussel
  • Dendermonde, Belgium, 9200
    • AZ Sint Blasius

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age ≥ 18 years
• Histological diagnosis of unifocal invasive breast carcinoma, no special type (ductal carcinoma)
• Tumor Staging: cT1-2N0M0
• Luminal A or B
• Candidate for breast conserving surgery
• N0-status confirmed by lymph node cytology

Exclusion Criteria:

• Multifocal/multicentric disease
• Prior thoracic radiotherapy
• Pregnancy
• SBR3 grading
• Triple negative status which benefit neoadjuvant chemotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: preoperative tomotherapy; This study is an open study investigating the effect on quality of life of a very short preoperative radiotherapy for early breast cancer, including approximately 24 women. Radiotherapy will be performed in 1 week and before the surgery in stead of following surgery.Preoperative radiotherapy has the advantage that the tumor is visible on imaging. This can result in smaller boost volumes. The surgery will follow shortly after termination of the radiotherapy, resulting in a very short treatment period.

Radiation: Tomotherapy; Dose prescription: Whole breast irradiation: 25 Gy in 5 daily fractions of 5 Gy Boost: 30 Gy in 5 daily fractions of 6 Gy The boost will be delivered as a simultaneous integrated boost (SIB). Target volumes: Clinical target volume (CTV) breast: defined by the soft tissue of the breast down to the pectoralis fascia, but excluding the skin and the underlying muscle, ribs, lung and heart. Gross tumor volume (GTV) boost: includes all gross tumor volume, as visible on computer tomography, mammography and/or magnetic resonance imaging (MRI). MRI imaging is preferentially performed in treatment position. CTV boost: includes the primary tumor, with a margin of 1.0 cm in all directions to encompass potential microscopic disease extension. The CTV boost excludes the skin, pectoralis muscle, ribs, lung and heart. Planning target volume (PTV): CTV plus a margin of 5 mm in all directions, but limited at 5 mm below the skin surface.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of the surgical procedure	Duration of the breast conserving surgery (lumpectomy + sentinel lymph node procedure)	from 2 to 8 days after the last radiotherapy session.
Quantity of blood lost	Quantity of blood that has been lost during the breast conservation surgery, performed 2 to 8 days after the last radiotherapy session.	from 2 to 8 days after the last radiotherapy session.
Dindo score	Post operative morbidity assessment according to Dindo, Demartines et al.	Week 6 after radiotherapy start
Wound disruption (yes/no)	Presence of wound disruption defined as skin dehiscence from any cause including seroma or hematoma.	up to 30 days post operative
Wound infection (yes/no)	Presence of wound infection, defined as: purulent drainage, cellulitis, abscess or wound requiring drainage, debriding, and antibiotics associated with a clinical diagnosis of infection.	up to 30 days post operative
Number of adverse events	Acute radiation toxicity measure	up to three months after radiotherapy start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QLQ-C30 questionnaire	Assessment of the quality of life, according to the QLQC30 questionnaire	week 3 after radiotherapy start
QLQ-C30 questionnaire	Assessment of the quality of life, according to the QLQC30 questionnaire	week 6 after radiotherapy start
EORTC QLQ-BR23 questionnaire	Assessment of the quality of life, according to the EORTC BR23 questionnaire	week 3 after radiotherapy start
EORTC QLQ-BR23 questionnaire	Assessment of the quality of life, according to the EORTC BR23 questionnaire	week 6 after radiotherapy start
Number of adverse events	Late toxicity measure	from three months after radiotherapy start till end of study (up to 1 years)
Local recurrence (yes/no)	Local control: presence of local cancer recurrence	up till the end of study (1 year)

Collaborators and Investigators

• Sponsor: Andre Nazac
• Investigators: Principal Investigator: Mark De Ridder, MD, CHU Brugmann/UZ Brussel

Publications and helpful links

General Publications

• Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.
• Bartelink H, Horiot JC, Poortmans PM, Struikmans H, Van den Bogaert W, Fourquet A, Jager JJ, Hoogenraad WJ, Oei SB, Warlam-Rodenhuis CC, Pierart M, Collette L. Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial. J Clin Oncol. 2007 Aug 1;25(22):3259-65. doi: 10.1200/JCO.2007.11.4991. Epub 2007 Jun 18.
• Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, Dobbs HJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Simmons S, Sydenham MA, Venables K, Bliss JM, Yarnold JR; START Trialists' Group. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol. 2013 Oct;14(11):1086-1094. doi: 10.1016/S1470-2045(13)70386-3. Epub 2013 Sep 19.
• Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, Shelley W, Grimard L, Bowen J, Lukka H, Perera F, Fyles A, Schneider K, Gulavita S, Freeman C. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010 Feb 11;362(6):513-20. doi: 10.1056/NEJMoa0906260.
• Versmessen H, Vinh-Hung V, Van Parijs H, Miedema G, Voordeckers M, Adriaenssens N, Storme G, De Ridder M. Health-related quality of life in survivors of stage I-II breast cancer: randomized trial of post-operative conventional radiotherapy and hypofractionated tomotherapy. BMC Cancer. 2012 Oct 25;12:495. doi: 10.1186/1471-2407-12-495.
• Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E, Zackrisson S, Cardoso F; ESMO Guidelines Committee. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015 Sep;26 Suppl 5:v8-30. doi: 10.1093/annonc/mdv298. No abstract available.
• Van Parijs H, Miedema G, Vinh-Hung V, Verbanck S, Adriaenssens N, Kerkhove D, Reynders T, Schuermans D, Leysen K, Hanon S, Van Camp G, Vincken W, Storme G, Verellen D, De Ridder M. Short course radiotherapy with simultaneous integrated boost for stage I-II breast cancer, early toxicities of a randomized clinical trial. Radiat Oncol. 2012 Jun 1;7:80. doi: 10.1186/1748-717X-7-80.
• van Mourik AM, Elkhuizen PH, Minkema D, Duppen JC; Dutch Young Boost Study Group, van Vliet-Vroegindeweij C. Multiinstitutional study on target volume delineation variation in breast radiotherapy in the presence of guidelines. Radiother Oncol. 2010 Mar;94(3):286-91. doi: 10.1016/j.radonc.2010.01.009. Epub 2010 Mar 2.
• Kirby AN, Jena R, Harris EJ, Evans PM, Crowley C, Gregory DL, Coles CE. Tumour bed delineation for partial breast/breast boost radiotherapy: what is the optimal number of implanted markers? Radiother Oncol. 2013 Feb;106(2):231-5. doi: 10.1016/j.radonc.2013.02.003. Epub 2013 Mar 13.
• Nichols EM, Dhople AA, Mohiuddin MM, Flannery TW, Yu CX, Regine WF. Comparative analysis of the post-lumpectomy target volume versus the use of pre-lumpectomy tumor volume for early-stage breast cancer: implications for the future. Int J Radiat Oncol Biol Phys. 2010 May 1;77(1):197-202. doi: 10.1016/j.ijrobp.2009.04.063.

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2017
• Primary Completion (Actual): March 3, 2022
• Study Completion (Actual): March 3, 2022

Study Registration Dates

• First Submitted: August 4, 2016
• First Submitted That Met QC Criteria: August 4, 2016
• First Posted (Estimate): August 8, 2016

Study Record Updates

• Last Update Posted (Actual): July 20, 2022
• Last Update Submitted That Met QC Criteria: July 19, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Radiotherapy; Short preoperative tomotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: CHUB-Preop-Breast

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No