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Background: We used two models to simulate a proposed noninferiority trial of radiotherapy (RT) omission in low-risk invasive breast cancer to illustrate how modeling could be used to predict the trial's outcomes, inform trial design, and contribute to practice debates.Methods: The proposed trial was a prospective randomized trial of no-RT vs RT in women age 40 to 74 years undergoing lumpectomy and endocrine therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative, stage I breast cancer with an Oncotype DX score of 18 or lower. The primary endpoint was recurrence-free interval (RFI), including locoregional recurrence, distant recurrence, and breast cancer death. Noninferiority required the two-sided 90% confidence interval of the RFI hazard ratio (HR) for no-RT vs RT to be entirely below 1.7. Model inputs included published data. The trial was simulated 1000 times, and results were summarized as percent concluding noninferiority and mean (standard deviation) of hazard ratios for Model GE and Model M, respectively.Results: Noninferiority was demonstrated in 18.0% and 3.7% for the two models. The respective means (SD) of the RFI hazard ratios were 1.8 (0.7) and 2.4 (0.9); most were locoregional recurrences. The mean five-year RFI rates for no-RT vs RT (SD) were 92.7% (2.9%) vs 95.5% (2.2%) and 88.4% (2.0%) vs 94.5% (1.6%). Both models showed little or no difference in breast cancer-specific or overall survival. Alternative definitions of low risk based on combinations of age and grade produced similar results.Conclusions: The proposed trial was unlikely to show noninferiority of omitting radiotherapy even using alternative definitions of low-risk, as the endpoint included local recurrence. Future trials regarding radiotherapy should address absolute reduction in recurrence and impact of type of recurrence on the patient. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy after breast conservation has become the standard of care. Prior meta-analyses on effects of radiotherapy predated availability of gene expression profiling (GEP) to assess recurrence risk and/or did not include all relevant outcomes. This analysis used GEP information with pooled individual-level data to evaluate the impact of omitting radiotherapy on recurrence and mortality.Methods: We considered trials that evaluated or administered radiotherapy after lumpectomy in women with low-risk breast cancer. Women included had undergone lumpectomy and were treated with hormonal therapy for stage I, ER+ and/or PR+, HER2- breast cancer with Oncotype scores no greater than 18. Recurrence-free interval (RFI), type of RFI (locoregional or distant), and breast cancer-specific and overall survival were compared between no radiotherapy and radiotherapy using adjusted Cox models. All statistical tests were two-sided.Results: The final sample included 1778 women from seven trials. Omission of radiotherapy was associated with an overall adjusted hazard ratio of 2.59 (95% confidence interval [CI] = 1.38 to 4.89, P = .003) for RFI. There was a statistically significant increase in any first locoregional recurrence (P = .001), but not distant recurrence events (P = .90), or breast cancer-specific (P = .85) or overall survival (P = .61). Five-year RFI rate was high (93.5% for no radiotherapy vs 97.9% for radiotherapy; absolute reduction = 4.4%, 95% CI = 0.7% to 8.1%, P = .03). The effects of radiotherapy varied across subgroups, with lower RFI rates for those with Oncotype scores of less than 11 (vs 11-18), older (vs younger), and ER+/PR+ status (vs other).Conclusions: Omission of radiotherapy in hormone-sensitive patients with low recurrence risk may lead to a modest increase in locoregional recurrence event rates, but does not appear to increase the rate of distant recurrence or death. [ABSTRACT FROM AUTHOR]

Purpose: To examine 10-year rates of local, regional, and distant recurrences, patterns of recurrence, and survival rates for breast cancer patients enrolled on Study NRG Oncology/Radiation Therapy Oncology Group 9517, a multi-institutional prospective trial that studied one of the earliest methods of accelerated partial breast irradiation (APBI), multicatheter brachytherapy (MCT).Methods and Materials: Eligibility included stage I/II unifocal breast cancer <3 cm in size after lumpectomy with negative surgical margins and 0 to 3 positive axillary nodes without extracapsular extension. The APBI dose delivered was 34 Gy in 10 twice-daily fractions over 5 days for high-dose-rate (HDR); and 45 Gy in 3.5 to 5 days for low-dose-rate (LDR) brachytherapy. The primary endpoint was HDR and LDR MCT reproducibility. This analysis focuses on long-term ipsilateral breast recurrence (IBR), contralateral breast cancer events (CBE), regional recurrence (RR), and distant metastases (DM), disease-free, and overall survival.Results: The median follow-up was 12.1 years. One hundred patients were accrued from 1997 to 2000; 98 were evaluable; 65 underwent HDR and 33 LDR MCT. Median age was 62 years; 88% had T1 tumors; 81% were pN0. Seventy-seven percent were estrogen receptor and/or progesterone receptor positive; 33% received adjuvant chemotherapy and 64% antiendocrine therapy. There have been 4 isolated IBRs and 1 IBR with RR, for 5.2% 10-year IBR without DM. There was 1 isolated RR, 1 with IBR, and 1 with a CBE, for 3.1% 10-year RR without DM. The 10-year CBE rate was 4.2%, with 5 total events. Eleven patients have developed DM, 8 have died of breast cancer, and 22 have died from other causes. The 10-year DFS and OS rates are 69.8% and 78.0%, respectively.Conclusion: This multi-institutional, phase 2 trial studying MCT-APBI continues to report durable in-breast cancer control rates with long-term follow-up. [ABSTRACT FROM AUTHOR]

Postmastectomy radiation therapy (PMRT) improves breast cancer survival in many women with lymph node-positive disease who undergo surgery followed by adjuvant chemotherapy. The role of PMRT after women receive neoadjuvant chemotherapy (NAC) is less clear. The available data suggest that clinical extent of disease at presentation before NAC, pathologic residual disease (especially pathologically involved lymph nodes) after NAC, and response to NAC are key prognostic factors for locoregional recurrence. Therefore, accurate axillary staging before the initiation of NAC and assessment of response to chemotherapy are critically important. Here, the authors review the literature addressing the radiotherapy management of patients with breast cancer who received NAC and underwent mastectomy with a special focus on the imaging modalities used to assess axillary lymph node status. Cancer 2015;121:1187-1194. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

Abstract: Hypofractionated radiation refers to treatment with greater than 2Gy per fraction, usually in fewer number and an overall shorter treatment period, compared to conventional radiation fractionation. Randomized prospective trials of hypofractionated whole breast irradiation (WBI) have demonstrated comparable outcomes as conventional fractionation in early stage postlumpectomy radiation in selected groups of patients. These data have changed the traditional radiobiology estimation of the alpha/beta ratio that predicted fractionation sensitivity for breast cancer, suggesting that further increase in dose per fraction is possible for early stage breast cancer without significantly increasing late effects. Many questions remain regarding hypofractionated WBI and span from optimal patient selection to radiation technique including dose planning optimization and the incorporation of a tumor bed boost. A concurrent radiation boost has been studied in a number of single institution studies and has shown to be feasible with acceptable acute and short-term late toxicity. A phase III trial by the Radiation Therapy Oncology Group (RTOG 1005) in North America and other trials in Europe are currently studying in-breast cancer control from hypofractionated WBI with a concurrent tumor bed boost. Results from these current trials could improve the acceptance and broaden the applicability of hypofractionation treatment courses for the treatment of patients with early stage breast cancer. [Copyright &y& Elsevier]

Abstract: Purpose: The Radiation Therapy Oncology Group (RTOG) has published consensus guidelines for contouring relevant anatomy for postmastectomy radiation therapy (RT). How these contours relate to current treatment practices is unknown. We analyzed the dose-volume histograms (DVHs) for these contours using current clinical practice at University of Texas MD Anderson Cancer Center and compared them with the proposed treatment plans to treat RTOG-defined targets to full dose. Methods and Materials: We retrospectively analyzed treatment plans for 20 consecutive women treated with postmastectomy RT for which the treatment targets were the chest wall (CW), level III axilla (Ax3), supraclavicular (SCV), and internal mammary (IM) nodes. The RTOG consensus definitions were used to contour the following anatomic structures: CW; level I, II, and III axillary nodes (Ax1, Ax2, Ax3); SCV; IM; and heart (H). DVHs for these contours and the ipsilateral lung were generated from clinically designed treatment that had actually been delivered to each patient. For comparison regarding dose to normal tissue, new treatment plans were generated with the goal of covering 95% of the anatomic contours to 45 Gy. Results: The prescribed dose was 50 Gy in each case. The mean percent of volumes that received 45 Gy (V45) for the RTOG guideline-based contours were CW 74%, Ax1 84%, Ax2 88%, Ax3 96%, SCV 84%, and IM 80%. Mean heart V10 values were 11% for treatment of left-sided tumors and 6% for right-sided tumors. Mean ipsilateral lung V20 values were 28% for left-sided tumors and 34% for right-sided tumors. For the contour-based plans, mean V45 values were CW 94%, Ax1 95%, Ax2 97%, Ax3 98%, SCV 98%, and IM 85%. Mean heart V10 values were 14% for treatment of left-sided tumors and 12% for right-sided tumors. Mean ipsilateral lung V20 values were 32% for left-sided tumors and 45% for right-sided tumors. Conclusions: Clinically derived treatment plans, which have proven efficacy and are the current standard, cover 74% to 96% of the anatomy-based RTOG consensus volumes to the prescription dose. This discrepancy should be considered if treatment planning protocol guidelines are designed to incorporate these new definitions. [Copyright &y& Elsevier]

Purpose: To examine the respiratory motion for target and normal structures during whole breast and nodal irradiation and the resulting dosimetric impact. Methods and Materials: Four-dimensional CT data sets of 18 patients with early-stage breast cancer were analyzed retrospectively. A three-dimensional conformal dosimetric plan designed to irradiate the breast was generated on the basis of CT images at 20% respiratory phase (reference phase). The reference plans were copied to other respiratory phases at 0% (end of inspiration) and 50% (end of expiration) to simulate the effects of breathing motion on whole breast irradiation. Dose–volume histograms, equivalent uniform dose, and normal tissue complication probability were evaluated and compared. Results: Organ motion of up to 8.8mm was observed during free breathing. A large lung centroid movement was typically associated with a large shift of other organs. The variation of planning target volume coverage during a free breathing cycle is generally within 1%–5% (17 of 18 patients) compared with the reference plan. However, up to 28% of V45 variation for the internal mammary nodes was observed. Interphase mean dose variations of 2.2%, 1.2%, and 1.4% were observed for planning target volume, ipsilateral lung, and heart, respectively. Dose variations for the axillary nodes and brachial plexus were minimal. Conclusions: The doses delivered to the target and normal structures are different from the planned dose based on the reference phase. During normal breathing, the dosimetric impact of respiratory motion is clinically insignificant with the exception of internal mammary nodes. However, noticeable degradation in dosimetric plan quality may be expected for the patients with large respiratory motion. [Copyright &y& Elsevier]

This study compared the 7 treatment plan options in achieving the dose-volume criteria required by the Radiation Therapy Oncology Group (RTOG) 1005 protocol. Dosimetry plans were generated for 15 representative patients with early-stage breast cancer (ESBC) based on the protocol-required dose-volume criteria for each of the following 7 treatment options: 3D conformal radiotherapy (3DCRT), whole-breast irradiation (WBI) plus 3DCRT lumpectomy boost, 3DCRT WBI plus electron boost, 3DCRT WBI plus intensity-modulated radiation therapy (IMRT) boost, IMRT WBI plus 3DCRT boost, IMRT WBI plus electron boost, IMRT WBI plus IMRT boost, and simultaneous integrated boost (SIB) with IMRT. A variety of dose-volume parameters, including target dose conformity and uniformity and normal tissue sparing, were compared for these plans. For the patients studied, all plans met the required acceptable dose-volume criteria, with most of them meeting the ideal criteria. When averaged over patients, most dose-volume goals for all plan options can be achieved with a positive gap of at least a few tenths of standard deviations. The plans for all 7 options are generally comparable. The dose-volume goals required by the protocol can in general be easily achieved. IMRT WBI provides better whole-breast dose uniformity than 3DCRT WBI does, but it causes no significant difference for the dose conformity. All plan options are comparable for lumpectomy dose uniformity and conformity. Patient anatomy is always an important factor when whole-breast dose uniformity and conformity and lumpectomy dose conformity are considered. [ABSTRACT FROM AUTHOR]

Purpose: NRG Oncology RTOG 0319 was the first cooperative group trial in the United States to evaluate 3-dimensional conformal radiation therapy (3D-CRT) accelerated partial breast irradiation (APBI). This report updates secondary endpoints of toxicity and efficacy.Methods and Materials: Patients with stage I or II invasive breast cancer (tumor size ≤3 cm, ≤3 positive lymph nodes, negative margins) were eligible for 3D-CRT APBI: 38.5 Gy in 10 twice-daily fractions. Patient characteristics and treatment details have previously been reported. Adverse events were graded with CTCAE v3.0 (National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0). This analysis updates the rates of ipsilateral breast recurrence (IBR), contralateral breast recurrence, ipsilateral node recurrence (INR), metastatic sites (distant metastases [DM]), mastectomy, disease-free survival, mastectomy-free survival, and overall survival.Results: Of 58 enrolled patients, 52 were eligible, with a median age of 61 years; 94% had stage I cancer and 83% had estrogen receptor positive disease. The median follow-up period was 8 years (minimum-maximum, 1.7-9.0 years). The 7-year estimate of isolated IBR (no DM) was 5.9%. The 7-year estimates of all IBRs, INR, mastectomy rate, and DM were 7.7%, 5.8%, 7.7%, and 7.7%, respectively. All 4 IBRs were invasive, of which 3 had a component within the planning target volume. The patterns of failure were as follows: 3 IBRs, 1 INR, 2 DM, 1 INR plus DM, and 1 IBR plus INR plus DM. The 7-year estimates of mastectomy-free survival, disease-free survival, and overall survival were 71.2%, 71.2%, and 78.8%, respectively. Thirteen patients died: 3 of breast cancer and 10 of other causes. Grade 3 (G3) treatment-related adverse events were reported by 4 patients (7.7%). No G3 pain or pulmonary or cardiac toxicities were reported.Conclusions: This phase 1 and 2 trial of 3D-CRT APBI continues to show durable tumor control and minimal G3 toxicity, comparable to other APBI techniques. Mature phase 3 results will determine the appropriateness and limitations of this noninvasive APBI technique. [ABSTRACT FROM AUTHOR]

Purpose: Obesity, as measured by the body mass index (BMI), is a risk factor for distant recurrence and decreased survival in breast cancer. We sought to determine whether the BMI correlated with local recurrence and reduced survival in a cohort of predominantly obese women treated with breast conservation therapy.Methods and Materials: From 1998 to 2010, 154 women with early-stage invasive breast cancer and 39 patients with ductal carcinoma in situ underwent prone whole breast irradiation. Cox proportional hazards regression, Kaplan-Meier methods with the log-rank test, and multivariate analysis were used to explore the association of the outcomes with the BMI.Results: The median patient age was 60 years, and the median follow-up duration was 73 months. The median BMI was 33.2 kg/m(2); 91% of the patients were overweight (BMI ≥25 kg/m(2)) and 69% of the patients were clinically obese (BMI ≥30 kg/m(2)). The BMI was significantly associated with the locoregional recurrence-free interval for patients with invasive cancer and ductal carcinoma in situ (hazard ratio [HR], 1.09; P=.047). Also, a trend was seen for increased locoregional recurrence with a higher BMI (P=.09) for patients with invasive disease, which was significant when examining the outcomes with a BMI stratified by the median value of 33.2 kg/m(2) (P=.008). A greater BMI was also significantly associated with decreased distant recurrence-free interval (HR, 1.09; P=.011) and overall survival (HR, 1.09; P=.004); this association remained on multivariate analysis (distant recurrence-free interval, P=.034; overall survival, P=.0007).Conclusions: These data suggest that the BMI might affect the rate of locoregional recurrence in breast cancer patients. A higher BMI predicted a worse distant recurrence-free interval and overall survival. The present investigation adds to the increasing evidence that BMI is an important prognostic factor in early-stage breast cancer treated with breast conservation therapy. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Radiation Therapy Oncology Group (RTOG) 95-17, a Phase II trial to evaluate multicatheter brachytherapy (mCathBrachy) as the sole method of radiation therapy for Stage I–II breast cancer (BrCa), was the first cooperative group trial in North America to evaluate accelerated partial breast irradiation (APBI) and include patient-reported outcomes (PROs). This report presents the year-5 toxicity and cosmesis data. Methods and Materials: After lumpectomy and axillary dissection for invasive BrCa (tumor size <3cm with zero to three positive lymph nodes), 100 patients (pts), 98 evaluable, were treated (txed) with mCathBrachy from 1997 to 2000 with 34Gy administered twice daily in 10 high-dose-rate fractions or 45Gy in 3.5–6 days as a low-dose-rate implant to 1–2cm beyond the lumpectomy bed. The PROs and physician-reported outcomes of toxicity, cosmesis, and tx satisfaction at year-5 are reported here, defined as data submitted 54–78 months after tx. Results: Grade (G) 1–2 skin toxicity developed in 78% of the pts and G3 in 13% (no G4). The tx effects included skin dimpling/indentation (37%), fibrosis (45%), telangiectasias (45%), skin catheter marks (54%), and symptomatic fat necrosis (15%). Breast asymmetry was reported in 73%. Rates of excellent-to-good cosmesis were similar between PROs (66%) and radiation oncologists (68%). The PROs of tx satisfaction at year-5 was 75%. Conclusions: RTOG 95-17 documents the year-5 skin toxicity and tx effects of mCathBrachy APBI, which are associated with PROs of good-to-excellent cosmesis and high tx satisfaction. This emphasizes the importance of PROs when assessing BrCa tx. National Surgical Adjuvant Breast and Bowel Project B39/RTOG 0413 will allow for definitive comparisons between APBI and whole breast radiation therapy. [Copyright &y& Elsevier]

Purpose: Late toxicities and cosmetic analyses of patients treated with accelerated partial breast irradiation (APBI) on RTOG 0319 are presented. Methods and Materials: Patients with stages I to II breast cancer ≤3 cm, negative margins, and ≤3 positive nodes were eligible. Patients received three-dimensional conformal external beam radiation therapy (3D-CRT; 38.5 Gy in 10 fractions twice daily over 5 days). Toxicity and cosmesis were assessed by the patient (P), the radiation oncologist (RO), and the surgical oncologist (SO) at 3, 6, and 12 months from the completion of treatment and then annually. National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to grade toxicity. Results: Fifty-two patients were evaluable. Median follow-up was 5.3 years (range, 1.7-6.4 years). Eighty-two percent of patients rated their cosmesis as good/excellent at 1 year, with rates of 64% at 3 years. At 3 years, 31 patients were satisfied with the treatment, 5 were not satisfied but would choose 3D-CRT again, and none would choose standard radiation therapy. The worst adverse event (AE) per patient reported as definitely, probably, or possibly related to radiation therapy was 36.5% grade 1, 50% grade 2, and 5.8% grade 3 events. Grade 3 AEs were all skin or musculoskeletal-related. Treatment-related factors were evaluated to potentially establish an association with observed toxicity. Surgical bed volume, target volume, the number of beams used, and the use of bolus were not associated with late cosmesis. Conclusions: Most patients enrolled in RTOG 0319 were satisfied with their treatment, and all would choose to have the 3D-CRT APBI again. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: External beam accelerated partial breast irradiation (EB-aPBI) is noninvasive with broader potential applicability than aPBI using brachytherapy. However, it has inherent challenges in daily reproducibility. Image-guide radiotherapy (IGRT) can improve daily reproducibility, allowing smaller treatment margins. Our institution proposed IG-IMRT in the prone position to evaluate dose homogeneity, conformality, normal tissue avoidance, and reliable targeting for EB-aPBI. We report preliminary results and toxicity from a phase I/II study evaluating the feasibility of EB-aPBI in the prone position using IG-IMRT. Materials and methods: Twenty post-menopausal women with node-negative breast cancer, excised tumors <3.0cm, negative sentinel lymph node biopsy, and surgical clips demarcating the lumpectomy cavity underwent prone EB-aPBI using IG-IMRT on an IRB-approved phase I/II study. All patients underwent CT planning in the prone position. The lumpectomy cavity PTV represented a 2.0cm expansion. 38.5Gy was delivered in 10 fractions over 5days, such that 95% of the prescribed dose covered >99% of the PTV. Dose constraints for the whole breast, lungs and heart were met. Results: The median patient age was 61.5. Mean tumor size was 1.0cm. 35% of patients had DCIS. Median PTV was 243cc (108–530) and median breast reference volume was 1698cc (647–3627). Average daily shifts for IGRT were (0.6, −4.6, 1.7mm) with standard deviations of (6.3, 6.5, 6.4mm). Acute toxicity was G1 erythema in 80%, and G2 erythema, G2 fatigue, and G2 breast pain each occurred in 1 patient. With a median follow-up of 18.9months (12–35), 40% of patients have G1 fibrosis and 30% have G1 hyperpigmentation. 95% of patients have good to excellent cosmesis. There have been no recurrences. Conclusions: These data demonstrate that EB-aPBI in the prone position using IG-IMRT is well tolerated, yields good dosimetric conformality, and results in promising early toxicity profiles. [Copyright &y& Elsevier]

Purpose: To report our institution''s experience using prone positioning for three-dimensional conformal radiotherapy (3D-CRT) to deliver post-lumpectomy whole breast irradiation (WBI) in a cohort of women with large and/or pendulous breasts, to determine the rate of acute and late toxicities and, more specifically, cosmetic outcomes. We hypothesized that using 3D-CRT for WBI in the prone position would reduce or eliminate patient and breast size as negative prognostic indicators for toxicities associated with WBI. Methods and Materials: From 1998 to 2006, 110 cases were treated with prone WBI using 3D-CRT. The lumpectomy, breast target volumes, heart, and lung were contoured on all computed tomography scans. A dose of 45–50 Gy was prescribed to the breast volume using standard fractionation schemes. The planning goals were ≥95% of prescription to 95% of the breast volume, and 100% of boost dose to 95% of lumpectomy planning target volume. Toxicities and cosmesis were prospectively scored using the Common Terminology Criteria for Adverse Effects Version 3.0 and the Harvard Scale. The median follow-up was 40 months. Results: The median body mass index (BMI) was 33.6 kg/m2, and median breast volume was 1396 cm3. The worst toxicity encountered during radiation was Grade 3 dermatitis in 5% of our patient population. Moist desquamation occurred in 16% of patients, with only 2% of patients with moist desquamation outside the inframammary/axillary folds. Eleven percent of patients had Grade ≥2 late toxicities, including Grade 3 induration/fibrosis in 2%. Excellent to good cosmesis was achieved in 89%. Higher BMI was associated with moist desquamation and breast pain, but BMI and breast volume did not impact fibrosis or excellent to good cosmesis. Conclusion: In patients with higher BMI and/or large–pendulous breasts, delivering prone WBI using 3D-CRT results in favorable toxicity profiles and high excellent to good cosmesis rates. Higher BMI was associated with moist desquamation, but prone positioning removed BMI and breast size as factors for poorer cosmetic outcomes. This series adds to the growing literature demonstrating that prone WBI may be advantageous in select patients. [Copyright &y& Elsevier]

Purpose: In patients with early-stage breast cancer treated with breast-conserving surgery, randomized trials have found little difference in local control and survival outcomes between patients treated with conventionally fractionated (CF-) whole breast irradiation (WBI) and those receiving hypofractionated (HF)-WBI. However, it remains controversial whether these results apply to all subgroups of patients. We therefore developed an evidence-based guideline to provide direction for clinical practice. Methods and Materials: A task force authorized by the American Society for Radiation Oncology weighed evidence from a systematic literature review and produced the recommendations contained herein. Results: The majority of patients in randomized trials were aged 50 years or older, had disease Stage pT1-2 pN0, did not receive chemotherapy, and were treated with a radiation dose homogeneity within ±7% in the central axis plane. Such patients experienced equivalent outcomes with either HF-WBI or CF-WBI. Patients not meeting these criteria were relatively underrepresented, and few of the trials reported subgroup analyses. For patients not receiving a radiation boost, the task force favored a dose schedule of 42.5 Gy in 16 fractions when HF-WBI is planned. The task force also recommended that the heart should be excluded from the primary treatment fields (when HF-WBI is used) due to lingering uncertainty regarding late effects of HF-WBI on cardiac function. The task force could not agree on the appropriateness of a tumor bed boost in patients treated with HF-WBI. Conclusion: Data were sufficient to support the use of HF-WBI for patients with early-stage breast cancer who met all the aforementioned criteria. For other patients, the task force could not reach agreement either for or against the use of HF-WBI, which nevertheless should not be interpreted as a contraindication to its use. [ABSTRACT FROM AUTHOR]

Purpose: This prospective study (Radiation Therapy Oncology Group 0319) examines the use of three-dimensional conformal external beam radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI). Initial data on efficacy and toxicity are presented. Methods and Materials: Patients with Stage I or II breast cancer with lesions ≤3 cm, negative margins and with ≤3 positive nodes were eligible. The 3D-CRT was 38.5 Gy in 3.85 Gy/fraction delivered 2×/day. Ipsilateral breast, ipsilateral nodal, contralateral breast, and distant failure (IBF, INF, CBF, DF) were estimated using the cumulative incidence method. Mastectomy-free, disease-free, and overall survival (MFS, DFS, OS) were recorded. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3, was used to grade acute and late toxicity. Results: Fifty-eight patients were entered and 52 patients are eligible and evaluable for efficacy. The median age of patients was 61 years with the following characteristics: 46% tumor size <1 cm; 87% invasive ductal histology; 94% American Joint Committee on Cancer Stage I; 65% postmenopausal; 83% no chemotherapy; and 71% with no hormone therapy. Median follow-up is 4.5 years (1.7–4.8). Four-year estimates (95% CI) of efficacy are: IBF 6% (0–12%) [4% within field (0–9%)]; INF 2% (0–6%); CBF 0%; DF 8% (0–15%); MFS 90% (78–96%); DFS 84% (71–92%); and OS 96% (85–99%). Only two (4%) Grade 3 toxicities were observed. Conclusions: Initial efficacy and toxicity using 3D-CRT to deliver APBI appears comparable to other experiences with similar follow-up. However, additional patients, further follow-up, and mature Phase III data are needed to evaluate the extent of application, limitations, and value of this particular form of APBI. [Copyright &y& Elsevier]

Purpose: To present guidance for patients and physicians regarding the use of accelerated partial-breast irradiation (APBI), based on current published evidence complemented by expert opinion. Methods and Materials: A systematic search of the National Library of Medicine''s PubMed database yielded 645 candidate original research articles potentially applicable to APBI. Of these, 4 randomized trials and 38 prospective single-arm studies were identified. A Task Force composed of all authors synthesized the published evidence and, through a series of meetings, reached consensus regarding the recommendations contained herein. Results: The Task Force proposed three patient groups: (1) a “suitable” group, for whom APBI outside of a clinical trial is acceptable, (2) a “cautionary” group, for whom caution and concern should be applied when considering APBI outside of a clinical trial, and (3) an “unsuitable” group, for whom APBI outside of a clinical trial is not generally considered warranted. Patients who choose treatment with APBI should be informed that whole-breast irradiation (WBI) is an established treatment with a much longer track record that has documented long-term effectiveness and safety. Conclusion: Accelerated partial-breast irradiation is a new technology that may ultimately demonstrate long-term effectiveness and safety comparable to that of WBI for selected patients with early breast cancer. This consensus statement is intended to provide guidance regarding the use of APBI outside of a clinical trial and to serve as a framework to promote additional clinical investigations into the optimal role of APBI in the treatment of breast cancer. [Copyright &y& Elsevier]

This summary focuses on the role of postoperative radiation therapy in patients treated with modified radical mastectomy for invasive breast cancer, particularly in patients receiving systemic therapy. [Copyright &y& Elsevier]

Purpose: To quantify the multi-institutional and multiobserver variability of target and organ-at-risk (OAR) delineation for breast-cancer radiotherapy (RT) and its dosimetric impact as the first step of a Radiation Therapy Oncology Group effort to establish a breast cancer atlas. Methods and Materials: Nine radiation oncologists specializing in breast RT from eight institutions independently delineated targets (e.g., lumpectomy cavity, boost planning target volume, breast, supraclavicular, axillary and internal mammary nodes, chest wall) and OARs (e.g., heart, lung) on the same CT images of three representative breast cancer patients. Interobserver differences in structure delineation were quantified regarding volume, distance between centers of mass, percent overlap, and average surface distance. Mean, median, and standard deviation for these quantities were calculated for all possible combinations. To assess the impact of these variations on treatment planning, representative dosimetric plans based on observer-specific contours were generated. Results: Variability in contouring the targets and OARs between the institutions and observers was substantial. Structure overlaps were as low as 10%, and volume variations had standard deviations up to 60%. The large variability was related both to differences in opinion regarding target and OAR boundaries and approach to incorporation of setup uncertainty and dosimetric limitations in target delineation. These interobserver differences result in substantial variations in dosimetric planning for breast RT. Conclusions: Differences in target and OAR delineation for breast irradiation between institutions/observers appear to be clinically and dosimetrically significant. A systematic consensus is highly desirable, particularly in the era of intensity-modulated and image-guided RT. [Copyright &y& Elsevier]

Purpose: The Radiation Therapy Oncology Group (RTOG) protocol 95-17 was a Phase I/II trial to evaluate multicatheter brachytherapy as the sole method of adjuvant breast radiotherapy for Stage I/II breast carcinoma after breast-conserving surgery. Low- or high-dose-rate sources were allowed. Dose prescription and treatment evaluation were based on recommendations in the International Commission on Radiation Units and Measurements (ICRU), Report 58 and included the parameters mean central dose (MCD), average peripheral dose, dose homogeneity index (DHI), and the dimensions of the low- and high-dose regions.Methods and Materials: Three levels of quality assurance were implemented: (1) credentialing of institutions was required before entering patients into the study; (2) rapid review of each treatment plan was conducted before treatment; and (3) retrospective review was performed by the Radiological Physics Center in conjunction with the study chairman and RTOG dosimetry staff.Results: Credentialing focused on the accuracy of dose calculation algorithm and compliance with protocol guidelines. Rapid review was designed to identify and correct deviations from the protocol before treatment. The retrospective review involved recalculation of dosimetry parameters and review of dose distributions to evaluate the treatment. Specifying both central and peripheral doses resulted in uniform dose distributions, with a mean dose homogeneity index of 0.83 +/- 0.06.Conclusions: Vigorous quality assurance resulted in a high-quality study with few deviations; only 4 of 100 patients were judged as representing minor variations from protocol, and no patient was judged as representing major deviation. This study should be considered a model for quality assurance of future trials. [ABSTRACT FROM AUTHOR]

Purpose: We present the results of the initial clinical testing of the MammoSite balloon breast brachytherapy applicator in women with early-stage breast cancer treated with breast-conserving therapy.Methods and Materials: Seventy patients were enrolled in a multicenter prospective trial testing the applicator for safety and performance. Fifty-four patients were implanted, and 43 patients were ultimately eligible for and received brachytherapy as the sole radiation modality after lumpectomy. Patients were staged T1N0M0 with negative pathologic margins and age >45 years. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using 192Ir high-dose-rate brachytherapy. A minimum skin-to-balloon surface distance of 5 mm was required for treatment. Device performance, complications, and cosmesis were assessed.Results: Computed tomography imaging post-balloon inflation showed 8, 14, and 21 patients with 5–6 mm, 7–9 mm, and >10 mm of skin spacing, respectively. Two patients were explanted because of inadequate skin spacing and 7 because of suboptimal conformance of the surgical cavity to the applicator balloon. One patient was explanted because of positive nodal status and another because of age. The most common side effects related to device placement included mild erythema, drainage, pain, and echymosis. No severe side effects related to implantation, brachytherapy, or explantation occurred. Side effects related to radiation therapy were generally mild with erythema, pain, and dry desquamation being the most common. At 1 month, 88% of patients were evaluated as having good-to-excellent cosmetic results.Conclusions: The MammoSite balloon breast brachytherapy applicator performed well clinically. All eligible patients completed treatment. Side effects were mild to moderate and self-limiting. Skin-balloon surface distance and balloon-cavity conformance were the main factors limiting the initial use of the device. [Copyright &y& Elsevier]