A prospective Phase III trial evaluating patient self-reported pain and cosmesis in accelerated partial breast irradiation utilizing 3-D versus intensity-modulated radiotherapy.

PURPOSE/OBJECTIVE: The primary objective is to examine patient self-assessment of breast pain and cosmesis between three-dimensional (3D-CRT) versus intensity-modulated radiotherapy (IMRT). The secondary objective is to evaluate any relationship of treatment planning conformality of both cohorts to patient-assessed pain. Assessments were performed at interim 12, 24, 36, and 48 months with a final 5-year assessment. MATERIALS/METHODS: In total, 656 patients (3D-CRT n = 328; IMRT n = 328) were randomly assigned to either IMRT or 3D-CRT accelerated partial breast radiotherapy to 38.5 Gy in 10 BID 3.85 Gy fractions. RESULTS: Median follow-up was 3 years. Multivariate analysis showed that pain severity significantly decreased from baseline to the 12-month follow-up visit (<0.001 for both 3D-CRT and IMRT) in each cohort. There was significantly less pain at 2 (p = 0.002) and 3 years (0.045) in the IMRT arm versus the 3D-CRT arm when compared to the baseline pain level. There was no difference in patient-assessed cosmesis at any follow-up point; however, although MD-assessed cosmesis showed no difference from years 1 to 4, there was significantly better cosmesis for 3D-CRT versus IMRT (p = 0.047) at 5 years. There was a significant correlation between a maximum pain score and an increase in the CI100 (indicating less conformity) in the IMRT cohort (p < 0.01) and in the IMRT subgroup when the CI100 was ≤0.37 cohort arm (p = 0.01). CONCLUSION: In the analysis of our primary objective we found that at 2 years, IMRT resulted in more interval improvement in breast pain after baseline when compared to patients treated with 3D-CRT planning. As seen in our secondary analysis, this may be due to the ability of IMRT to achieve higher conformality (as evidenced by lower CI values) resulting in less fibrosis. There were no differences in patient-assessed cosmesis or MD-assessed cosmesis for years 1-4; however, physician-assessed 5-year cosmesis was better with 3D-CRT.

External beam accelerated partial breast irradiation yields favorable outcomes in patients with prior breast augmentation.

PURPOSE: To report outcomes in breast cancer patients with prior breast augmentation treated with external beam accelerated partial breast irradiation (EB-APBI) utilizing intensity-modulated radiotherapy or 3-dimensional conformal radiotherapy, both with IGRT. MATERIALS AND METHODS: Sixteen stage 0/1 breast cancer patients with previous elective bilateral augmentation were treated post-lumpectomy on institutional EB-APBI trials (01185132 and 01185145 on clinicaltrials.gov). Patients received 38.5 Gy in 10 fractions over five consecutive days. Breast/chest wall pain and cosmesis were rated by patient; cosmesis was additionally evaluated by physician per RTOG criteria. RESULTS: The median follow-up from accelerated partial breast irradiation (APBI) completion was 23.9 months (range, 1.2-58.6). Little to no change in cosmesis or pain from baseline was reported. Cosmetic outcomes at last follow-up were judged by patients as excellent/good in 81.2% (13/16), and by physicians as excellent/good in 93.8% (15/16). Ten patients (62.5%) reported no breast/chest wall pain, five (31.2%) reported mild pain, and one (6.2%) reported moderate pain. All patients remain disease free at last follow-up. The median ipsilateral breast, planning target volume (PTV), and implant volumes were 614, 57, and 333 cm(3). The median ratios of PTV/ipsilateral breast volume (implant excluded) and PTV/total volume (implant included) were 9 and 6%. CONCLUSION: These 16 breast cancer cases with prior bilateral augmentation treated with EB-APBI demonstrate favorable clinical outcomes. Further exploration of EB-APBI as a treatment option for this patient population is warranted.

Four-year clinical update from a prospective trial of accelerated partial breast intensity-modulated radiotherapy (APBIMRT).

This prospective Phase II single-arm study gathered data on the use of intensity-modulated radiotherapy (IMRT) to deliver accelerated partial breast irradiation (APBI). Four-year efficacy, cosmesis, and toxicity results are presented. Between February 2004 and September 2007, 136 consecutive patients with Stage 0/I breast cancer and negative margins ≥0.2 cm were treated on protocol. Patients received 38.5 Gy in 10 equal fractions delivered twice daily. Breast pain and cosmesis were rated by patient, and cosmesis was additionally evaluated by physician per Radiation Therapy Oncology Group (RTOG) criteria. The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v3.0) was used to grade toxicities. 136 patients (140 breasts) with median follow-up of 53.1 months (range, 8.9-83.2) were evaluated. Population characteristics included median age of 61.9 years and Tis (13.6 %), T1a (18.6 %), T1b (36.4 %), and T1c (31.4 %). Kaplan-Meier estimates at 4 years: ipsilateral breast tumor recurrence 0.7 %; contralateral breast failure 0 %; distant failure 0.9 %; overall survival 96.8 %; and cancer-specific survival 100 %. At last follow-up, patients and physicians rated cosmesis as excellent/good in 88.2 and 90.5 %, respectively; patients rated breast pain as none/mild in 97.0 %. Other observations included edema (1.4 %), telangiectasia (3.6 %), five cases of grade 1 radiation recall (3.6 %), and two cases of rib fractures (1.4 %). This analysis represents the largest cohort and longest follow-up of APBI utilizing IMRT reported to date. Four-year results continue to demonstrate excellent local control, survival, cosmetic results, and toxicity profile.

Accelerated partial breast intensity-modulated radiotherapy in women who have prior breast augmentation.

PURPOSE: To examine the outcome of breast cancer patients who have prior breast augmentation treated with lumpectomy followed by accelerated partial breast external intensity-modulated radiotherapy (APBIMRT) with image-guided radiotherapy (IGRT). METHODS AND MATERIALS: Four patients with previous elective subpectoral breast augmentation were enrolled on this APBIMRT trial. These four patients were treated with 10 equal twice daily 3.85 Gy fractions over 5 consecutive days (total dose of 38.5 Gy) using APBIMRT and IGRT. Patients were assessed for pain and cosmetic outcome (physician and a patient self-assessment). RESULTS: At last follow-up, two patients reported an excellent cosmetic results (at 2 years and at 8 months, respectively), one reported good cosmetic results (at 2 years), and one reported poor cosmetic results (at 20 months). Physicians rated the cosmetic outcomes as excellent in two (CEL; at 2 years and 8 months, respectively), good in one (CEL; at 20 months) and excellent in one (KTH; at 2 years). Three patients reported no breast/chest wall pain (two at 2 years and one at 1 year) and the fourth reported mild pain (at 20 months). The mean percent volume of ipsilateral breast receiving 100%, 75%, 50%, and 25% of the prescribed dose was 7.28%, 17.55%, 24.33%, and 33.1%, respectively. The mean breast, planning target volume (PTV), and implant volumes were 399.88 cc, 43.55 cc, and 313.36 cc, respectively. The mean breast prosthesis/total volume (breast tissue plus prosthesis) ratio was 44.55%. The mean PTV/ipsilateral breast and PTV/total volume ratios were 11.1% and 6.1%, respectively. CONCLUSION: The results show that a regimen of APBIMRT with IGRT is possible in patients who have prior breast augmentation.

Clinical experience with image-guided radiotherapy in an accelerated partial breast intensity-modulated radiotherapy protocol.

PURPOSE: To explore the feasibility of fiducial markers for the use of image-guided radiotherapy (IGRT) in an accelerated partial breast intensity modulated radiotherapy protocol. METHODS AND MATERIALS: Nineteen patients consented to an institutional review board approved protocol of accelerated partial breast intensity-modulated radiotherapy with fiducial marker placement and treatment with IGRT. Patients (1 patient with bilateral breast cancer; 20 total breasts) underwent ultrasound guided implantation of three 1.2- x 3-mm gold markers placed around the surgical cavity. For each patient, table shifts (inferior/superior, right/left lateral, and anterior/posterior) and minimum, maximum, mean error with standard deviation were recorded for each of the 10 BID treatments. The dose contribution of daily orthogonal films was also examined. RESULTS: All IGRT patients underwent successful marker placement. In all, 200 IGRT treatment sessions were performed. The average vector displacement was 4 mm (range, 2-7 mm). The average superior/inferior shift was 2 mm (range, 0-5 mm), the average lateral shift was 2 mm (range, 1-4 mm), and the average anterior/posterior shift was 3 mm (range, 1 5 mm). CONCLUSIONS: This study shows that the use of IGRT can be successfully used in an accelerated partial breast intensity-modulated radiotherapy protocol. The authors believe that this technique has increased daily treatment accuracy and permitted reduction in the margin added to the clinical target volume to form the planning target volume.

Predictors for clinical outcomes after accelerated partial breast intensity-modulated radiotherapy.

PURPOSE: To correlate the treatment planning parameters with the clinical outcomes in patients treated with accelerated partial breast intensity-modulated radiotherapy. METHODS AND MATERIALS: A total of 105 patients with Stage I breast cancer were treated between February 2004 and March 2007 in a Phase II prospective trial and had detailed information available on the planning target volume (PTV), ipsilateral breast volume (IBV), PTV/IBV ratio, lung volume, chest wall volume, surgery to radiotherapy interval, follow-up interval, breast pain, and cosmesis. The first 7 of these patients were treated to 34 Gy, and the remaining 98 were treated to 38.5 Gy. All patients were treated twice daily for 5 consecutive days. Univariate and multivariate analyses were performed. RESULTS: The median follow-up was 13 months. No recurrences or deaths were observed. Of the 105 patients, 30 reported mild or moderate breast pain in their most recently recorded follow-up visit. The irradiated lung volume (p < 0.05) and chest wall volume receiving >35 Gy (p < 0.01) were associated with pain. The PTV, but not the PTV/IBV ratio, also correlated with pain (p < 0.01 and p = 0.42, respectively). A total of 72 patients reported excellent, 32 reported good, and 1 reported poor cosmesis. Physician-rated cosmesis reported 90 excellent and 15 good. None of the tested variables correlated with the cosmetic outcomes. CONCLUSION: Radiotherapy to the chest wall (chest wall volume receiving >35 Gy) and to lung correlated with reports of mild pain after accelerated partial breast intensity-modulated radiotherapy. Also, the PTV, but not the PTV/IBV ratio, was predictive of post-treatment reports of pain.

Accelerated partial-breast intensity-modulated radiotherapy results in improved dose distribution when compared with three-dimensional treatment-planning techniques.

PURPOSE: To compare dose distribution and normal tissue sparing in partial-breast treatment using three-dimensional conformal radiotherapy (3D-CRT) vs. intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Sixty-three patients with Tis-1N0M0 breast cancer were treated on a Phase II prospective accelerated partial-breast IMRT protocol at two facilities between April 2004 and January 2006. Fifty-six patients had data sets sufficient to adequately contour all structures. These cases were subsequently replanned with 3D-CRT techniques using the same contours, to compare the dose distribution patterns of 3D-CRT vs. IMRT. RESULTS: The average planning target volume (PTV) to ipsilateral breast (IB) ratio was 24% (range, 7-58%). The average volume of IB receiving 25%, 50%, 75%, and 100% of the prescribed dose was 4.0%, 5.0%, 5.5%, and 10.5% less with IMRT than with 3D (p < 0.01). The dose reduction to normal breast was further improved in the subset of patients whose PTV to IB ratio was >25%, and in patients with contoured breast volume <750 cm(3). No difference was detected in delivery to the lumpectomy cavity or clinical target volume. The PTV volume receiving 95% of the dose was higher in the 3D conformal plans (p < 0.01), but no significant difference was observed in the PTV volume receiving 90% (p = 0.17). The irradiated heart and lung volumes were small with both techniques but also favored IMRT. CONCLUSIONS: In T1N0 patients treated with external beam partial-breast radiotherapy, IMRT improves normal tissue sparing in the ipsilateral breast compared with 3DRT, without compromising dose delivery to the lumpectomy cavity and clinical target volume.

Prospective trial of accelerated partial breast intensity-modulated radiotherapy.

PURPOSE: To examine the feasibility and acute toxicities of an accelerated, partial breast, intensity-modulated radiotherapy (IMRT) protocol. METHODS AND MATERIALS: Between February 2004 and August 2005, 55 patients with Stage I breast cancer and initial follow-up were enrolled at four facilities on a HealthONE and Western institutional review board-approved accelerated partial breast IMRT protocol. All patients were treated in 10 equal fractions delivered twice daily within 5 consecutive days. The first 7 patients were treated to 34 Gy, and the remaining 48 patients were treated to 38.5 Gy. RESULTS: The median follow-up after IMRT was 10 months (range, <1-19) and after diagnosis was 11.5 months (range, 2-21). No local or distant recurrences developed. The T stage distribution was as follows: T1a in 11 patients, T1b in 24, and T1c in 20. The median tumor size was 9 mm (range, 1-20 mm). Breast cosmesis was judged by the patient as poor by 2, good by 12, and excellent by 40 (1 patient was legally blind) and by the physician as poor for 1, good for 10, and excellent for 44 patients. Breast pain, as judged by patient, was none in 34, mild in 19, moderate in 2, and severe in 0 patients. There was a single report of telangiectasia but no incidents of significant edema. Compared with historic controls for whom three-dimensional treatment planning techniques were used, IMRT provided similar dose delivery to the target while reducing the volume of normal breast included in the 100%, 75%, and 50% isodose lines. CONCLUSION: This initial report prospectively explored the feasibility of accelerated partial breast IMRT. After short-term follow-up, the dose delivery and clinical outcomes were very acceptable. We believe this regimen deserves additional investigation under institutional review board guidance.

Excision only for tubular carcinoma of the breast.

The purpose of this study was to assess the rationale of excision only (without breast irradiation) in patients with small (< or =3 cm) tubular/well-differentiated breast cancers. A total of 44 patients with pure tubular invasive breast cancer who have undergone complete excision only and have had a minimum 1-year follow-up were identified from the Colorado Cancer Registry and assessed for recurrence rates as well as median local disease-free and overall survival. Treatment dates were October 1972 to April 2001. The median age was 67 years (range 40-96 years). The median tumor size was 6.5 mm (range 2-30 mm). All patients had a complete excision with negative margins. Staging was as follows: T1N0 (11), T1Nx (27), T2N0 (1), T1N1 (3); 2 were unable to be staged accurately. After a median follow-up of 5.4 years (range 1.1-26.3 years) there were only two local recurrences in the ipsilateral breast (at 7.6 and 8.8 years), for a crude local control rate of 96% (2/44). Both patients were salvaged, are alive, and currently have no evidence of disease (NED) at last follow-up of 9 and 13.3 years. Actuarial 5- and 10-year local control rates were 100% and 87%. Actuarial 5- and 10-year overall and disease-free survivals were 80% and 52%, and 100% and 91%. Twenty-five patients had more than 5 years of follow-up. The median follow-up for this group was 9.1 years (range 5.1-26.3 years) and both recurrences were in this group. Although the number of cases in this report is small, it represents the largest total and longest follow-up for tubular breast cancer cases after excision alone. This report suggests that breast irradiation could be omitted after conservative surgery in older patients with smaller (< or =3 cm) tubular/well-differentiated breast cancers. However, due to the retrospective nature of our report, we cannot categorically make this recommendation.