Clinical trial NCT00981864: Concurrent Boost Radiotherapy
Official title: A Feasibility Study to Evaluate Intensity Modulated Radiation Therapy (IMRT) for Concomitant Boost Breast Radiotherapy (CBRT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: radiation therapy in breast cancer
concurrent radiation
Breast cancer patients
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Princess Margaret Hospital, Canada
First posted: 2009-09-22
Enrollment: 17
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary aim of this study is to evaluate the feasibility of delivering 42.5 Gy to the breast with a concomitant 10 Gy boost to the tumour bed in 16 fractions for a total duration of 3.5 weeks using intensity modulated radiotherapy (IMRT). The primary end-point is the proportion of patients treated without major treatment deviation.

Detailed description: Rather than a sequential boost, we propose delivering a concomitant boost using intensity modulated radiotherapy (IMRT). IMRT is a sophisticated technique deliberately using multiple non-uniform beams, resulting in complex, conformal dose distributions. This technique offers several advantages. A concomitant IMRT boost potentially offers improved dose distributions by allowing more conformal doses around the boost volume and increased sparing of the remaining breast and adjacent organs at risk. Several studies have shown better target dose homogeneity resulting in less toxicity with adjuvant breast IMRT . One study found a significant reduction in the rates of moist desquamation with IMRT compared to wedged tangential fields (31% vs. 48%, P=0.0014).

Longer treatment duration increases the inconvenience and decreases patient compliance. Furthermore, this places extra financial and emotional hardship on the patient and her family, particularly if they must travel long distances between home and the treatment centre. Studies have found 10-30% of patients do not receive adjuvant radiotherapy after lumpectomy,placing these patients at higher risk for local recurrence and death from disease. Radiobiologically, a boost increases the risk of late normal tissue effects. In the EORTC study, they found significantly higher but limited rates of severe fibrosis at 10 years of 4.4% vs. 1.6% (p\<0.0001) with the boost. No age effect was noted on the incidence of fibrosis. One study compared a shorter hypofractionated schedule of 42.5 Gy/16 fractions over 3.5 weeks with the standard schedule of 50 Gy/25 fractions over 5 weeks and observed comparable 5 year local recurrence rates and cosmetic outcomes.

Eligibility criteria: Inclusion Criteria:

1. Female patient with a new histological diagnosis of invasive carcinoma OR ductal carcinoma-in-situ (DCIS) of the breast and no evidence of metastatic disease.
2. Any of the following indications for boost radiotherapy to tumour bed:

   1. Age ≤ 60 years
   2. Positive or close resection margins (≤ 2 mm)
   3. Lymphovascular space invasion
   4. Extensive intraductal component (DCIS \>25% of tumour volume)
3. Three or fewer axillary nodes involved as determined either by:

   1. Sentinel node biopsy OR
   2. Axillary node dissection OR
   3. Clinical exam for patients with DCIS only or age greater than 70 years of age.
4. Informed consent.

Exclusion Criteria:

1. Age \< 18 years.
2. Seroma or surgical cavity on CT estimated to be \> 30% of the breast volume.
3. More than one primary tumour in different quadrants of the same breast.
4. Previous irradiation to the ipsilateral breast that would preclude whole breast irradiation.
5. Presence of an ipsilateral breast implant or pacemaker.
6. Serious non-malignant disease (e.g. cardiovascular, pulmonary, systemic lupus erythematosus (SLE), scleroderma) which would preclude definitive radiation treatment.
7. For patients not treated with adjuvant chemotherapy: unable to commence radiation therapy within 12 weeks of the last surgical procedure on the breast.
8. For patients treated with adjuvant chemotherapy: unable to commence within 8 weeks of the last dose of chemotherapy.
9. Previous or concomitant malignancies except for patients with nonmelanoma skin cancer, contralateral non-invasive breast cancer or carcinoma in situ of any other site. In addition, patients with invasive cancers treated more than 5 years previously and without evidence of recurrence will be eligible.
10. Currently pregnant or lactating.
11. Psychiatric or addictive disorders which would preclude obtaining informed consent or adherence to protocol.
12. Geographic inaccessibility for follow-up.
13. Regional lymphatic irradiation planned.

Primary outcomes:
measure: To evaluate the feasibility of delivering 42.5 Gy to the breast with a concomitant 10 Gy boost to the tumour bed in 16 fractions without major treatment deviation.
timeFrame: 2 years
Secondary outcomes:
measure: To evaluate acute and late morbidity related to treatment
timeFrame: 2 years
measure: To identify factors and parameters associated with increased risk of treatment morbidity
timeFrame: 2 years
measure: To evaluate local control rates
timeFrame: 2 years
measure: To develop treatment protocol outlining appropriate guidelines for planning and delivery
timeFrame: 2 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network, Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Princess Margaret Hospital
name: Fei-Fei Liu, MD
role: PRINCIPAL_INVESTIGATOR
References: