RAPID: Randomized Trial of Accelerated Partial Breast Irradiation
RAPID: Randomized Trial of Accelerated Partial Breast Irradiation
To determine if Accelerated Partial Breast Irradiation, using 3D CRT, is as effective as
 Whole Breast Irradiation following breast conserving surgery in women with an new
 histological diagnosis of ductal carcinoma in situ only or invasive breast cancer without
 evidence of metastatic disease. Effectiveness will be determined by the rate of ipsilateral
 breast tumour recurrence.

 General objective is to improve the convenience and quality of life of female patients who
 receive breast irradiation.
Following breast conserving surgery or on completion of chemotherapy, patients will be
 stratified according to age, tumour histology, tumour size, adjuvant hormonal therapy and
 clinical centre. Patients will be allocated to receive either whole breast irradiation or 3D
 CRT accelerated partial breast irradiation.

 Radiation therapy will be administered as soon as possible following the healing of the
 surgical incision (3-4 weeks) and within 12 weeks if the patient is not treated with
 chemotherapy. If the patient is treated with chemotherapy, radiation therapy will begin after
 2 weeks and not beyond 8 weeks after the last dose of chemotherapy.

 Patients treated with whole breast irradiation will receive a total dose of 42.5 Gy in 16
 fractions, given on a daily basis, over a time period of 22 days. Patients with large breast
 size are permitted to receive a total dose of 50 Gy in 25 fractions, given on a daily basis,
 over a time period of 35 days. Boost irradiation is permitted in patients treated with whole
 breast irradiation. Boost irradiation of 10 Gy/4-5 fractions daily over a time period of 4-7
 days is permitted for patients deemed at moderate to high risk of local recurrence as per
 local cancer centre guidelines.

 Patients treated with 3D CRT accelerated partial breast irradiation will receive a total dose
 of 38.5 Gy in 10 fractions, delivered twice a day, over a time period of 5-8 days. Each daily
 dose must be separated by 6-8 hours.

 Patients will be followed indefinitely and assessed formally at 6 and 12 months after the
 date of randomization and then on a yearly basis. Patients will be assessed for acute and
 late radiation toxicity, cardiac toxicity, recurrent disease, new primary cancer, cosmetic
 outcome, quality of life and overall survival.
Inclusion Criteria:

 -  1a. Female patient with a new histological diagnosis of DCIS only. OR

 1b. Female patient with a new histological diagnosis of invasive carcinoma of the
 breast and no evidence of metastatic disease.

 2. Treated by BCS with microscopically clear resection margins for invasive and
 non-invasive disease (or no residual disease on re- excision).

 3. Negative axillary node involvement including micrometastasis <= 0.2mm or positive
 cells only identified by IHC as determined either by: (i) sentinel node biopsy (ii)
 axillary node dissection or (iii) clinical exam for patients with DCIS only

 Exclusion Criteria:

 -  1. Age < 40 years.

 2. A known deleterious mutation in BRCA 1 and/or BRCA 2.

 3. Tumour size > 3 cm in greatest diameter on pathological examination (including both
 the invasive and non-invasive component).

 4. Tumour histology limited to lobular carcinoma only.

 5. History of cancer:

 -  Patients with another active malignancy or malignancy treated < 5 years prior to
 randomization are excluded.

 -  Patients with a prior diagnosis of invasive or non-invasive breast cancer in
 either breast are excluded regardless of disease free interval. Patients with
 concurrent invasive or non-invasive contralateral breast cancer are also
 excluded.

 -  Patients with prior or concurrent basal cell or squamous cell skin cancers are
 eligible for the trial.

 6. More than one primary tumour in different quadrants of the same breast.

 7. Previous irradiation to the ipsilateral breast that would preclude whole
 breast irradiation.

 8. Presence of an ipsilateral breast implant or pacemaker.

 9. Serious non-malignant disease (e.g. cardiovascular, pulmonary, systemic lupus
 erythematosus (SLE), scleroderma) which would preclude definitive radiation
 treatment.

 10. Estrogen receptor status (ER) not known.

 11. For patients not treated with adjuvant chemotherapy: unable to commence
 radiation therapy within 12 weeks of the last surgical procedure on the breast.

 12. For patients treated with adjuvant chemotherapy: unable to commence within 8
 weeks of the last dose of chemotherapy.

 13. Currently pregnant or lactating.

 14. Psychiatric or addictive disorders which would preclude obtaining informed
 consent or adherence to protocol.

 15. Geographic inaccessibility for follow-up.

 16. Inability to localize surgical cavity on CT (i.e., no evidence of surgical
 clips or seroma).

 17. Inability to adequately plan the patient for the experimental technique.