Seroma Cytology in Breast Cancer: An Underappreciated Issue.

BACKGROUND: The presence of malignant cells in postoperative seroma has been ignored in current breast cancer treatment. We aimed to assess the presence of malignant seroma cytology and to evaluate its relationship with the known prognostic factors for breast cancer. PATIENTS AND METHODS: The solution from irrigation of the operation field and postoperative drainage fluid from 68 patients were prospectively collected and examined for malignant cytology. The results were evaluated according to the tumor characteristics and patient demographics. RESULTS: Malignant cytology was found in none of the intraoperative samples but was found in the postoperative samples from 4 patients. Of these 4 patients, 3 were free of axillary metastasis. None of the common risk factors for breast cancer was associated with the finding of malignant cytology. CONCLUSION: Malignant cells can be seen in the drainage fluids from breast cancer patients independent of any contamination occurring during surgery, even in those without axillary metastasis.

Does breast composition influence late adverse effects in breast radiotherapy?

BACKGROUND: Large breast size is associated with increased risk of late adverse effects after surgery and radiotherapy for early breast cancer. It is hypothesised that effects of radiotherapy on adipose tissue are responsible for some of the effects seen. In this study, the association of breast composition with late effects was investigated along with other breast features such as fibroglandular tissue distribution, seroma and scar. METHODS: The patient dataset comprised of 18 cases with changes in breast appearance at 2 years follow-up post-radiotherapy and 36 controls with no changes, from patients entered into the FAST-Pilot and UK FAST trials at The Royal Marsden. Breast composition, fibroglandular tissue distribution, seroma and scar were assessed on planning CT scan images and compared using univariate analysis. The association of all features with late-adverse effect was tested using logistic regression (adjusting for confounding factors) and matched analysis was performed using conditional logistic regression. RESULTS: In univariate analyses, no statistically significant differences were found between cases and controls in terms of breast features studied. A statistically significant association (p < 0.05) between amount of seroma and change in photographic breast appearance was found in unmatched and matched logistic regression analyses with odds ratio (95% CI) of 3.44 (1.28-9.21) and 2.57 (1.05-6.25), respectively. CONCLUSIONS: A significant association was found between seroma and late-adverse effects after radiotherapy although no significant associations were noted with breast composition in this study. Therefore, the cause for large breast size as a risk factor for late effects after surgery and optimally planned radiotherapy remains unresolved.

Report on the Clinical Outcomes of Permanent Breast Seed Implant for Early-Stage Breast Cancers.

PURPOSE: Permanent breast seed implant is an accelerated partial breast irradiation technique realizing the insertion of (103)Pd seeds in the seroma after lumpectomy. We report the 5-year efficacy and tolerance for a cohort, pooling patients from 3 clinical trials. METHODS AND MATERIALS: The trials accrued postmenopausal patients with infiltrating ductal carcinoma or ductal carcinoma in situ ≤3 cm and clear surgical margins, who were node negative, and had a planning target volume <120 cm(3). The outcomes included overall and disease-free survival and local and contralateral recurrence at 5 years. The true local recurrence rate was compared using 2-tailed paired t tests for estimates calculated using the Tufts University ipsilateral breast tumor recurrence and Memorial Sloan Kettering ductal carcinoma in situ nomograms. RESULTS: The cohort included 134 patients, and the observed local recurrence rate at a median follow-up period of 63 months was 1.2% ± 1.2%, similar to the estimate for whole breast irradiation (P=.23), significantly better than for surgery alone (relative risk 0.27; P<.001), and significantly lower than contralateral recurrence (relative risk 0.33; P<.001). The 5-year overall survival rate was 97.4% ± 1.9%, and the disease-free survival rate was 96.4% ± 2.1%. At 2 months, 42% of the patients had erythema, 20% induration, and 16% moist desquamation. The rate of mainly grade 1 telangiectasia was 22.4% at 2 years and 24% at 5 years. The rate of asymptomatic induration was 23% at 2 years and 40% at 5 years. CONCLUSIONS: The 5-year data suggest that permanent breast seed implantation is a safe accelerated partial breast irradiation option after lumpectomy for early-stage breast cancer with a tolerance profile similar to that of whole breast irradiation.

[Comparison of the volume and localization of internal gross target volume and planning target volume delineated by clips and seroma based on 4D-CT scan for external-beam partial breast irradiation after breast conserving surgery].

OBJECTIVE: To explore the differences in volume and localization of the internal gross target volume and planning target volume delineated by clips and/or seroma based on four-dimensional computed tomography (4D-CT) during free-breathing in breast cancer patients after breast conserving surgery. METHODS: Fifteen breast cancer patients after breast-conserving surgery (BCS) were recruited for external-beam partial breast irradiation (EB-PBI). On the ten sets CT images, the gross tumor volumes (GTV) formed by the clips, the seroma, and both the clips and seroma were delineated and defined as GTVc, GTVs and GTVc+s, respectively. Ten GTVc, GTVs and GTVc+s on the ten sets CT images produced the IGTVc, IGTVs, IGTVc+s. The PTVc, PTVs, PTVc+s were created by adding 15 mm to the IGTVc, IGTVs, IGTVc+s, respectively. The IGTV and PTV volume and distance between the centers of IGTVc, IGTVs, IGTVc+s and PTVc, PTVs, PTVc+s were all recorded. Conformity index (CI) and degree of inclusion (DI) were calculated for IGTV/IGTV and PTV/PTV, respectively. RESULTS: The volume of IGTVc+s[(35.73 ± 19.77) cm³] was significantly larger than the IGTVc [(28.35 ± 17.54) cm³] and IGTVs [(24.19 ± 21.53) cm³] (P < 0.05), and the volume of PTVc+s [(191.59 ± 69.74) cm³] was significantly larger than that of the PTVc [(161.53 ± 61.07) cm³] and PTVs [(148.98 ± 62.22)cm³] (P < 0.05). There were significant differences between the DIs of IGTVc in IGTVc+s and IGTVc+s in IGTVc, the DIs of IGTVs in IGTVc+s and IGTVc+s in IGTVs, the DIs of PTVc in PTVc+s and PTVc+s in PTVc, and the DIs of PTVs vs. PTVc+s and PTVc+s in PTVs (P < 0.05 for all). The CI of IGTVc/IGTVc+s (0.63 ± 0.14) and the CI of IGTVs/IGTVc+s (0.54 ± 0.17) were significant larger than that of the CI of IGTVc/IGTVs (0.40 ± 0.14)(P < 0.05). There were non-significant differences among the CI of PTVc/PTVs, PTVc/PTVc+s and PTVs/PTVc+s (0.73 ± 0.12, 0.78 ± 0.13 vs. 0.75 ± 0.17). The DIs and CIs of IGTV/IGTV and PTV/PTV were negatively correlated with their centroid distance (P < 0.05). CONCLUSIONS: There are volume difference and spatial mismatch between the target volumes delineated on the basis of surgical clips and seroma. The DI and CI between the PTVs are larger than that between the IGTV. External-beam partial breast irradiation should be implemented based on the PTV that is defined based on both seroma and surgical clips.

Displacement of the lumpectomy cavity defined by surgical clips and seroma based on 4D-CT scan for external-beam partial breast irradiation after breast-conserving surgery: a comparative study.

OBJECTIVE: To compare the displacements of the lumpectomy cavity delineated by the surgical clips and the seroma based on four-dimensional CT (4D-CT) for external-beam partial breast irradiation (EB-PBI) after breast-conserving surgery (BCS). METHODS: 14 breast cancer patients after BCS were recruited for EB-PBI and undertook 4D-CT simulation. On the 10 sets of the 4D-CT images, all the surgical clips in the cavity were delineated. The gross tumour volume (GTV) formed by the clips, the seroma, and both the clips and the seroma were defined as GTVc, GTVs and GTVc+s, respectively. The displacements of the centre of mass (COM) of the clips, GTVc, GTVs, GTVc+s and the selected clips in the three-dimensional (3D) directions were recorded and compared. RESULTS: In the left-right, anterior-posterior and superior-inferior directions, the displacements were 2.20, 1.80 and 2.70 mm for the clip COM; 0.90, 1.05 and 1.20 mm for GTVc; 0.80, 1.05 and 0.80 mm for GTVs; and 0.90, 1.20 and 1.40 mm for GTVc+s, respectively. In the 3D directions, the displacements of the clip COM were greater than the GTVc, GTVs, GTVc+s, and the displacements of the clip COM, GTVc+s, GTVc and GTVs were significantly greater than the displacements of the selected clips (p<0.05). CONCLUSION: The displacements of the clip COM were greater than that of the GTVc, GTVs, GTVc+s and the four selected clips. The optimal internal target volume should be defined based on the boundary displacements. ADVANCES IN KNOWLEDGE: When the GTV was delineated using the clips and/or the seroma, there was displacement difference between the lumpectomy cavity centre and the boundary for the EB-PBI. The optimal internal target volume should be defined based on the boundary displacements of the lumpectomy cavity.

Evaluation of dosimetric consequences of seroma contour variability in accelerated partial breast irradiation using a constructed representative seroma contour.

PURPOSE: Contouring variability of the seroma can have important implications in the planning and delivery of accelerated partial breast irradiation (APBI). This study aimed to quantify the dosimetric impact of these interobserver and intraobserver contouring variations by construction of a representative seroma contour (RSC). METHODS AND MATERIALS: Twenty-one patients with a seroma suitable for APBI underwent four computed tomography (CT) scans: one planning CT and three additional CTs on the first, third, and fifth days of treatment. Three radiation oncologists contoured the seroma on each CT scan. For 3 patients, oncologists repeated contouring twice to assess intraobserver variations. Seroma contour variability was quantified by construction of an RSC. In addition, the percent volume overlap (PVO) was calculated. Root-mean-square (RMS) differences in seroma volume, size, and center of mass position compared to those of the RSC were calculated. Treatment fields from the original plan were applied to the repeated CTs by using the same isocenter shifts as the original plan. The dosimetric impact of the contour variations was assessed using V(95) (volume receiving at least 95% of the prescribed dose) and equivalent uniform dose (EUD). RESULTS: Interobserver RMS volume differences were, on average, 5.6 times larger than intraobserver differences. The median interobserver RMS seroma volume difference was 1.48 cm(3). The median PVO was 51.6%. V(95) and EUD of the seroma contours were similar for all patients. The median RMS differences of the seroma V(95) and EUD were 0.01% (range, 0%-3.99%) and 0.05 Gy (range, 0-0.98 Gy). CONCLUSIONS: Construction of the RSC showed that interobserver variations were most responsible for contour variations of the seroma. Current planning margins provided adequate dose coverage of the seroma despite these contour variations.

Clinical factors associated with seroma volume reduction in breast-Conserving Therapy for early-stage breast cancer: a multi-institutional analysis.

PURPOSE: To correlate clinical factors with seroma volume and reduction; and to determine whether cone-beam CT (CBCT) could be used clinically to monitor seroma reduction. PATIENTS AND METHODS: This investigation included 102 women from five institutions with stage T1-2 breast cancer treated with breast-conserving therapy. Two CT scans were acquired: the planning CT (CT1) and a second CT (CT2) during radiotherapy (RT). Seroma was contoured on all scans, and correlations between seroma characteristics and clinical factors were investigated by univariate and multivariate analyses. In a substudy, 10 of the 102 patients received multiple CBCT scans during RT. Seroma were contoured by two observers in the substudy. Fifteen time points at which CT and CBCT were performed within 2 days were identified. The levels of correlation in seroma contours between CBCT and CT and between the two observers were examined. RESULTS: The mean relative seroma reduction from CT1 to CT2 was 54% (p < 0.001). A significant inverse relationship was found between relative seroma reduction per week and number of RT fractions given by univariate and multivariate analyses (p = 0.01, 0.03). The mean difference in contoured seroma volumes between CT and CBCT was 12% (3.3 cm(3)). When assessing the relative difference in seroma contours between Observer 1 and Observer 2, an interobserver difference of 12% was demonstrated. Neither discrepancy was clinically significant. CONCLUSIONS: Radiotherapy seems to hinder seroma reduction. Volume discrepancies between CBCT and CT were minor, with low interobserver variation, indicating that CBCT might be useful in monitoring seroma reduction.

Change in seroma volume during whole-breast radiation therapy.

PURPOSE: After breast-conserving surgery, a seroma often forms in the surgical cavity. If not drained, it may affect the volume of tumor bed requiring a boost after whole-breast radiation therapy (WBRT). Our objective was to evaluate the change in seroma volume that occurs during WBRT, before boost planning. METHODS AND MATERIALS: A retrospective review was performed of women receiving breast-conserving therapy with evidence of seroma at the time of WBRT planning. Computed tomography (CT) simulation was performed before WBRT and before the tumor bed boost. All patients received either a hypofractionated (42.4 Gy/16 fraction + 9.6 Gy/4 fraction boost) or standard fractionated (50.4 Gy/28 fraction + 10 Gy/5 fraction boost) regimen. Seroma volumes were contoured and compared on CT at the time of WBRT simulation and tumor bed boost planning. RESULTS: Twenty-four patients with evidence of seroma were identified and all patients received WBRT without drainage of the seroma. Mean seroma volume before WBRT and at boost planning were significantly different at 65.7 cm(3) (SD, 50.5 cm(3)) and 35.6 cm(3) (SD, 24.8 cm(3)), respectively (p < 0.001). Mean and median reduction in seroma volume during radiation were 39.6% (SD, 23.8%) and 46.2% (range, 10.7-76.7%), respectively. Fractionation schedule was not correlated with change in seroma volume. Length of time from surgery to start of radiation therapy showed an inverse correlation with change in seroma volume (Pearson correlation r = -0.53, p < 0.01). CONCLUSIONS: The volume of seroma changes significantly during WBRT. Consequently, the accuracy of breast boost planning is likely affected, as is the volume of normal breast tissue irradiated. CT-based boost planning before boost irradiation is suggested to ensure appropriate coverage.

Changes in excision cavity volume: prediction of the reduction in absolute volume during breast irradiation.

PURPOSE: The aim of this study was to determine the changes in the excision cavity volume due to the resolution of the surgical effects during the whole breast treatment. MATERIALS AND METHODS: Seventy-seven patients with early-stage (T1-2 N0) breast cancer treated with breast-conserving therapy were included for this study. All patients underwent a standard planning computed tomography (CT) scan before irradiation treatment. A second CT scan was performed in the week before the start of the boost. Excision cavity volumes were delineated based on the surgical clips and the (surrounding) seroma or hematoma or other surgical changes on both scans by an experienced physician. This resulted in the gross tumor volumes GTV1 and GTV2. RESULTS: The delineated volumes of the GTVs were on average 78.7 cm(3) (range, 1.1-236.0 cm(3)) and 29.7 cm(3) (range, 1.3-123.6 cm(3)) for, respectively, GTV1 and GTV2. The time between the CT scans was on average 37 days (range, 29-74 days). This resulted in a reduction of on average 62%. The absolute reduction per day of the GTV1 was -1.3 cm(3)/day (range, 0.3 to -5.4 cm(3)/day). A linear correlation (correlation coefficient r(2) = 0.81) was observed between the absolute volume of GTV1 and the absolute reduction per day. CONCLUSION: A significant reduction in excision cavity volume during whole breast irradiation was shown. The observed correlation might be helpful in the decision to perform a second CT scan to adapt the treatment plan.

When is CT-based postoperative seroma most useful to plan partial breast radiotherapy? Evaluation of clinical factors affecting seroma volume and clarity.

PURPOSE: To evaluate the effect of the time from surgery and other clinical factors on seroma volume and clarity and establish the optimal time to use the computed tomography (CT)-based seroma to plan partial breast irradiation (PBI). METHODS AND MATERIALS: A total of 205 women with early-stage breast cancer underwent planning CT after breast-conserving surgery. One radiation oncologist contoured the seroma volume and scored the seroma clarity, using a standardized Seroma Clarity Score scale, from 0 (not detectable) to 5 (clearest). Univariate and multivariate analyses were performed to evaluate the associations between the seroma characteristics and the interval from surgery and other clinical factors. RESULTS: The mean interval from surgery to CT was 84 days (standard deviation 59). During postoperative Weeks 3-8, the mean seroma volume decreased from 47 to 30 cm(3), stabilized during Weeks 9-14 (mean 21) and was involuted beyond 14 weeks (mean 9 cm(3)). The mean seroma clarity score was 3.4 at Weeks 3-8, 2.5 at Weeks 9-14, and 1.6 after 14 weeks. The seroma clarity was greater in patients aged >or=70 years. The seroma volume and clarity correlated significantly with the volume of excised breast tissue but not with the maximal tumor diameter, surgical re-excision, or chemotherapy use. CONCLUSION: The optimal time to obtain the planning CT scan for PBI is within 8 weeks after surgery. During Weeks 9-14, the seroma might remain adequately defined in some patients; however, after 14 weeks, alternate strategies are needed to identify the PBI target. The lack of correlation between the seroma volume and tumor size suggests that the CT-based seroma should not be the sole guide for PBI target volume definition.

Interfractional dose variation due to seromas in radiotherapy of breast cancer.

We investigated the interfractional dose variation due to seromas in radiotherapy of breast cancer patients. For 3 patients who received seroma aspiration during the period of radiotherapy, 2 sets of computed tomography (CT) scanning images were obtained before and after seroma aspiration. Three sets of plans employing a conventional technique and an intensity-modulated radiotherapy (IMRT) technique were generated: the first set of plans was the optimal plan for the CT images before seroma aspiration, the second set was the plans that applied the treatment parameters with the first plans but used CT images obtained after seroma treatment, and the third set was the optimal plans for CT images taken after seroma treatment. From the analysis of each set of plans, we found that the patient anatomy change had little effect on the prescription dose (1-2% variation for both techniques) but had significant effects on the dose homogeneity in the treatment volume, which increased the dose inhomogeneity up to 13.9% for conventional treatment and 20.7% for IMRT treatment, respectively.