Between May 1, 2007 and August 31, 2011, 123 women consented to participate, of whom 2 were ineligible (1 bilateral breast surgery, 1 retracted consent). Of the 121 eligible, 62 were assigned to conventional RT, 59 to short-course IGRT. For the present study, two patients had no follow-up physical therapy assessment, and one patient with a baseline weight of 150 kg was excluded, on consideration of that extreme outlying value relative to other patients’ weight range which was 42–102 kg, leaving 118 patients evaluable for analyses. One patient had a contralateral arm paralysis since childhood, the scapular distance and arm mobility could not be measured and were assigned as missing values. One patient was confined to a wheelchair at pre-RT assessment, retroflexion was not measurable and was assigned as missing value. Two patients had pre-RT measurements of retroflexion exceeding 90°, the corresponding records could not be checked, these were also assigned as missing values.
Follow-up cutoff date was October 14, 2011. Median times of physical therapy assessment were 38 days (interquartile range IQR 31–45) from surgery to first physical therapy (baseline) assessment, 6 days (IQR 3–9) from baseline to start of RT, and 105 days (IQR 93–121) between baseline and the first post-RT follow-up. summarizes the patients’ characteristics. The age distribution of the patients enrolled in the trial tended to be younger than patients treated in the institution,38
reflecting that older patients were reluctant to accept randomization. Nevertheless, patients older than 70 years represented a substantial 12.7% of patients recruited. Regarding body mass index, half of the study population were overweight. Arm symptoms were present prior to RT in 18.6%. Half of the patients received breast conserving surgery with sentinel nodes biopsy only.
Distribution of the Δ RIDs showed for volume that 28% (=33/118) of the patients had a Δ volume RID exceeding 5% (CTCAE grade 1 limb edema). Excess Δ volume RID was on the ipsilateral limb (positive Δ volume RID) in 19 (=58% of 33) patients, on the contralateral limb in the other 14 (=42% of 33) patients (negative Δ volume RID indicating a relative volume increase of the contralateral limb). By CTCAE grade 2 or more limb edema, Δ volume RID exceeding 10% was observed on the ipsilateral limb in 5% (=6/118) and on the contralateral limb in 3% (=3/118) of the patients (, top left histogram). Regarding mobility, Δ RID exceeded 10% on the ipsilateral limb by abduction in 21% (=25/117), retroflexion in 22% (=25/114), by anteflexion in 17% (=20/117), by endorotation in 23% (=28/114), and by scapular distance in 17% (=20/117) of the patients. Δ RID exceeded 10% on the contralateral limb by abduction in 15% (=18/117), retroflexion in 25% (=29/114), by anteflexion in 3% (=4/117), by endorotation in 31% (=35/114), and by scapular distance in 21% (=24/117) of the patients (, other histograms). Considering combined Δ RIDs exceeding 10%, 25% (=29/118) of the patients had at least one of volume or abduction impairment of the ipsilateral limb, and 18% (=21/118) had at least a volume or abduction impairment of the contralateral limb.
Distributions of the pre- to post-radiotherapy changes (Δ) of the relative interlimb differences (RID).
Comparisons of the means of pre- and post-RT measurements found no significant changes between baseline and 2-months follow-up, other than a significant mean weight increase of 0.8 kg and a contralateral arm loss of abduction of 6 degrees (). Notably, none of the arm volume assessments either by absolute measure or by relative difference showed a significant change.
Arm and shoulder changes from pre to post-radiotherapy.
Multivariate correlations among the different measurements and between ipsilateral and contralateral arms are displayed in . The corresponding graphical display is shown in –. In order to interpret the correlations, we need to recall the conventions that we used: morbidity is indicated by increases of measurements regarding arm volume, endorotation, and scapular distance, whereas morbidity is indicated by decreases of measurements of abduction, retroflexion, and anteflexion. Hence, the significant correlations indicated concordant impairments within the ipsilateral arm (ipsilateral vs. ipsilateral, upper left quarter of ): increase of arm volume correlated with loss of abduction (correlation coefficient R = −0.32) and impairment of scapular movement (R = 0.19). Likewise, concordant impairments were noted between abduction, anteflexion, and endorotation. Retroflexion however showed no significant correlation. Within the contralateral arm (contralateral vs. contralateral, lower right quarter of ), a similar relationship was noted between arm volume and abduction (R = −0.24), and between arm volume and scapular distance (R = 0.32). Impairment of abduction significantly correlated with anteflexion, endorotation, and scapular distance in the same limb. No significant correlation was found for the contralateral retroflexion.
Ipsilateral and contralateral correlations (95% confidence intervals) of shoulder-arm Δ changes.
Correlations among ipsilateral shoulder-arm changes.
Correlations between ipsilateral and contralateral shoulder-arm changes.
Comparison of ipsilateral vs. contralateral arm shows that changes affecting one limb strongly correlated with changes affecting the other limb (upper right quarter of ). The highest correlations were abduction (R = 0.78), retroflexion (R = 0.73), scapular distance (R = 0.65), and arm volume (R = 0.57), all P-values <0.001. Other correlations also indicated concordant impairments. The only discordant exception that we found was the −0.16 coefficient between ipsilateral retroflexion and contralateral abduction.
Results of the exploratory analyses according to the type of response outcome are summarized in .
Risk factors of shoulder-arm changes from baseline.
By RIDs, only the presence of pre-RT arm symptoms was identified as a significant factor. The sign of the coefficient for the presence of pre-RT arm symptoms indicated that pre-RT arm symptoms were associated with improved ipsilateral abduction and anteflexion, relatively to the contralateral arm.
By absolute assessments, increased body weight and axillary lymph node dissection were positively associated with change of arm volume, ipsilaterally as well as contralaterally. Axillary lymph node dissection was associated with impairment of ipsilateral and contralateral scapular movement. Radiotherapy to regional nodes was associated with impaired ipsilateral abduction, while aromatase inhibitor therapy was associated with impaired contralateral abduction. The presence of pre-RT arm symptoms was associated with improved ipsilateral abduction, anteflexion, and endorotation. We also note an association between mastectomy and improvement of ipsilateral anteflexion and contralateral scapular distance.