Trial Outcomes & Findings for Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer (NCT NCT03414970)

Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer

The primary endpoint of this trial is the rate of ipsilateral breast reconstruction complications defined (in the protocol in 10.0. Measurement of effect) as; Capsular contracture (Baker Grade III or IV only), Complete failure of the implant/skin flap, Unplanned admission for reconstruction related issue(s) including but not limited to infection, wound healing complication or pain, Unplanned return to the operating room for recon related issue including but not limited to infection, prosthesis exposure, failed reconstruction, implant removal, wound healing complications or contracture management. Note: Routine revisions such as dog-ear corrections, fat grafting, and contralateral breast revision will be recorded, but not counted towards the primary endpoint; ii) Complications related to the contralateral breast will be collected but will not count towards the assessment of the primary endpoint, ipsilateral breast complications will be counted towards the primary endpoint.

The proportion of patients with acute or late radiation complications, will be estimated separately by treatment arm and will be compared across the two arms using two-sample test of proportions (Z test) with a two-sided alternative.

The cumulative incidence of local and local regional recurrence will be estimated separately by treatment arm using the cumulative incidence function treating death as the competing risk and will be compared using Gray's test.

Local and local regional recurrence free survival rate at three years will be summarized for each arm using the Kaplan-Meier estimators, and will be compared using a log rank test. Any recurrence or death will be considered an event.

Between-arm differences in reconstruction complication rates will be assessed separately within each of the six subgroups based on type and timing of reconstruction. Between-arm differences in complication rates will also be assessed within the two broader subgroups of patients who receive implant only and those who receive autologous based reconstruction. Within each subgroup, the comparison will be done using a two-sample Z test of proportions with a two-sided alternative.

Two year photographic cosmetic scores will be summarized by treatment arm and will be compared across the treatment arms using a Wilcoxon rank-sum test with a two-sided alternative. The proportions of patients with poor global cosmetic score (defined as a cosmetic score of 3: poor or large difference) at 24 months after radiation will be summarized separately by treatment arm and will be compared using a two-sample test of proportions with a two-sided alternative.

Two year photographic cosmetic scores and the proportions of patients with poor global cosmetic score will be assessed separately by timing and method of reconstruction subgroups using similar method described above.

The proportions of patients with arm lymphedema (defined as a change of 10% or greater in ipsilateral arm volume from the pre-radiation therapy \[RT\] volume) at 2 year post radiation will be summarized and will be compared across the two treatment arms using a two-sample test of proportions (Z test) with a two-sided alternative. Change in ipsilateral arm volume at each of the following time-points: 6, 12, 24 and 60 months post-radiation (relative to pre-RT) will be compared using a two sample t-test with a two-sided alternative. The changes in arm volume at these time points will also be analyzed as a repeated measure using a linear mixed model with patient as the random effect.

Change in Lymphedema and Breast Cancer Questionnaire and Breast Lymphedema scores at 24 months post-radiation (relative to pre-RT) and patient satisfaction scores as measured by the Breast Questionnaire overall outcome scale will be summarized and will be compared across the treatment arms using a two-sample t-test with a two-sided alternative. Linear mixed models will also be used to assess these scores longitudinally.

Was It Worth It questionnaire responses to each of the five questions at 24 months will be summarized and the will be compared across treatment arms using a chi-square tests with a two-sided alternative.

Direct costs of medical care to each patient will be estimated using utilization information from the health care expense survey and the health care utilization survey, along with publicly available Medicare reimbursement rates. In particular, based on the reported number of outpatient visits to the radiation oncologist, medical oncologist, surgeon who performed mastectomy, plastic surgeon or physical therapist, and the number of visits to the emergency room, the number of hospital admissions, and the number of surgical procedures to breast reconstruction, Medicare reimbursement rates can be used to estimate what the direct cost to each patient would be if that patient were covered by Medicare. Generalized linear models will then be used to model these costs as a function of treatment, time on study, and all available baseline patient characteristics to assess the extent to which estimated direct cost is impacted by the type of radiation dosing.