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To investigate patterns of failure in institutional credentialing submissions to NRG/RTOG 1005 with the aim of improving the quality and consistency for future breast cancer protocols. NRG/RTOG 1005 allowed the submission of 3-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), and simultaneous integrated boost (SIB) breast plans. Credentialing required institutions to pass a 2-step quality assurance (QA) process: (1) benchmark, requiring institutions to create a plan with no unacceptable deviations and ≤1 acceptable variation among the dose volume (DV) criteria, and (2) rapid review, requiring each institution's first protocol submission to have no unacceptable deviations among the DV criteria or contours. Overall rates, number of resubmissions, and reasons for resubmission were analyzed for each QA step. In total, 352 institutions participated in benchmark QA and 280 patients enrolled had rapid review QA. Benchmark initial failure rates were similar for 3DCRT (18%), IMRT (17%), and SIB (18%) plans. For 3DCRT and IMRT benchmark plans, ipsilateral lung most frequently failed the DV criteria, and SIB DV failures were seen most frequently for the heart. Rapid review contour initial failures (35%) were due to target rather than organs at risk. For 29% of the rapid review initial failures, the planning target volume boost eval volume was deemed an unacceptable deviation. The review of the benchmark and rapid review QA submissions indicates that acceptable variations or unacceptable deviations for the ipsilateral lung and heart dose constraints were the most commonly observed cause of benchmark QA failure, and unacceptable deviations in target contouring, rather than normal structure contouring, were the most common cause of rapid review QA failure. These findings suggest that a rigorous QA process is necessary for high quality and homogeneity in radiation therapy in multi-institutional trials of breast cancer to ensure that the benefits of radiation therapy far outweigh the risks. [ABSTRACT FROM AUTHOR]

Purpose As indications for regional nodal irradiation (RNI) for breast cancer have expanded, so too has scrutiny over potential late toxicity from radiotherapy. This emphasizes the need for careful radiation treatment planning to maximize the therapeutic ratio. We sought to evaluate how often unacceptable doses (UDs) to organs at risk (OARs) occur and the associated factors for patients receiving RNI in daily practice. Methods and materials Treatment records of patients who received RNI from February 2012 to May 2015 were studied. The NSABP B51/RTOG 1304 clinical dose-volume constraints for targets/OARs receiving RNI were used as the benchmark. Dose-volume histograms were analyzed for the rate of ≥1 UD delivered to the following organs: heart, mean >5 Gy; ipsilateral lung, V20 >35%, V10 >60%, V5 >70%; contralateral lung (CL), V5 >15%; and contralateral breast, V4.1 >5%. Logistic regression was used to test the association between UDs to OAR and key variables. Results Two hundred three consecutive cases received RNI (105 left, 98 right), to the chest wall in 171 (84%) and to the internal mammary nodes in 170 (84%); 77.4% of cases met all OAR constraints. The most common OAR UDs were delivered to the contralateral breast (n = 32, 15.7%) and ipsilateral lung V5 (n = 22, 10.8%). On multivariate analysis, use of intensity modulated radiation therapy (odds ratio [OR], 64.7; 95% confidence interval, 20.8-201.5; P < .001) and use of nodal boost (OR, 5.5; 95% confidence interval, 1.1-27.1; P = .04), but not internal mammary node irradiation (OR, 2.7; P = .35) or reconstruction (OR, 0.62; P = .33), were independently associated with higher OAR UD rate. For 3-dimensional conformal radiation therapy plans, 7.9% had OAR UDs. Conclusion The OAR UD rate with 3-dimensional conformal radiation therapy ± deep inspiration breath-hold in routine clinical practice is low and not independently associated with internal mammary node irradiation or reconstruction presence. Women treated with intensity modulated radiation therapy had a significantly higher overall OAR UD rate, and clinicians should be aware of this as they initiate RNI treatment planning. [ABSTRACT FROM AUTHOR]

Purpose To update the accelerated partial breast irradiation Consensus Statement published in 2009 and provide guidance on use of intraoperative radiation therapy (IORT) for partial breast irradiation in early-stage breast cancer, based on published evidence complemented by expert opinion. Methods and materials A systematic PubMed search using the same terms as the original Consensus Statement yielded 419 articles; 44 articles were selected. The authors synthesized the published evidence and, through a series of conference calls and e-mails, reached consensus regarding the recommendations. Results The new recommendations include lowering the age in the “suitability group” from 60 to 50 years and in the “cautionary group” to 40 years for patients who meet all other elements of suitability (Table 1). Patients with low-risk ductal carcinoma in situ, as per Radiation Therapy Oncology Group 9804 criteria, were categorized in the “suitable” group. The task force agreed to maintain the current criteria based on margin status. Recommendations for the use of IORT for breast cancer patients include: counseling patients regarding the higher risk of ipsilateral breast tumor recurrence with IORT compared with whole breast irradiation; the need for prospective monitoring of long-term local control and toxicity with low-energy radiograph IORT given limited follow-up; and restriction of IORT to women with invasive cancer considered “suitable.” Conclusion These recommendations will provide updated clinical guidance regarding use of accelerated partial breast irradiation for radiation oncologists and other specialists participating in the care of breast cancer patients. [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]

When surgery is the first line of breast cancer treatment, numerous randomized clinical trials and meta-analyses have demonstrated that postmastectomy radiation therapy (PMRT) improves locoregional control and survival for many women with axillary lymph node–positive disease. In contrast, there are no randomized data regarding the use of PMRT in women who receive neoadjuvant chemotherapy (NAC) first followed by mastectomy. This has led to controversy regarding which patient with breast cancer will benefit from PMRT after NAC, particularly in women with clinically node-positive axillary disease that responds well and is down staged to pathologically negative disease at surgery (ypN0). We review the current evidence on this topic, which forms the underlying basis for the ongoing phase III clinical trial—National Surgical Adjuvant Breast and Bowel Project (NSABP) B51/RTOG 1304—that is examining the role of regional nodal irradiation in patients with clinical N1 disease that responds to NAC and becomes ypN0 at surgery. [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]

Abstract: Background: Despite the high efficacy of the levonorgestrel-releasing intrauterine system (LNG-IUS) in preventing pregnancy, uptake of the intrauterine devices remains low in the United States. Decreasing pain at the time of intrauterine device insertion may be one way to increase interest in this method of contraception. Study Design: We conducted a double-blind, placebo-controlled trial, randomizing women to 800 mg ibuprofen or placebo 45 min prior to LNG-IUS insertion to determine effect of ibuprofen on the pain of LNG-IUS insertion. Results: Eighty-one women completed the study: 44 received ibuprofen, and 37 received placebo. Women in the ibuprofen and placebo groups had similar mean scores for anticipated pain (4.07 and 3.91, respectively; p=.79), pain with tenaculum placement (3.86 and 3.81, respectively; p=.90) and pain with insertion (3.69 and 3.34, respectively; p=.91). Conclusion: Administration of ibuprofen prophylaxis for LNG-IUS insertion does not decrease pain at the time of insertion. [Copyright &y& Elsevier]

Abstract: Purpose: Low α/β ratio for breast cancer has drawn a growing interest for exploring hypofractionation for breast irradiation. This work is to confirm the low α/β ratio based on large randomized clinical trials of breast irradiation. Methods and materials: A model based on the generalized linear-quadratic (LQ) model and Poisson statistical model was developed to calculate disease-free survival with consideration of clonogen proliferation during the course of radiation treatment and exponential behavior of survival rate with follow-up time. Outcome data from a series of randomized clinical trials of early-stage breast radiotherapy were fitted to estimate the model parameters. Other clinical outcomes, including treatments with surgery alone or radiotherapy alone were used to validate the model and the estimated parameters. Hypofractionation regimens were proposed based on the newly estimated LQ parameters. Results: Plausible population averaged radiobiologic parameters for breast cancer (95% confidence level) are α/β =2.88 (0.75–5.01) Gy; α =0.08±0.02Gy−1; potential doubling time T d =14.4±7.8day. The analysis of the radiation-alone data suggested an α/β ratio of 3.89±6.25Gy, verifying the low α/β ratio based on the post-lumpectomy irradiation data. The hypofractionation regimens that are equivalent to the conventional regimen of 2.0Gy×25 in 5weeks include 2.26Gy×20, 3.34Gy×10, 4.93Gy×5 or 3.39Gy×10 (BID). Conclusions: The analysis of the available clinical data from multiple institutions support that breast cancer has a low ratio of α/β, encouraging hypofractionated radiotherapy regimens for breast cancer. [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]

Purpose: Quality Research in Radiation Oncology™ (QRRO™) has embarked on a new national process survey to provide benchmark data that will allow radiation oncologists to assess the quality of care in their own practices by measuring quality indicators (QIs) and comparing individual with national practice. Methods: Investigators at QRRO developed QIs on the basis of nationally recognized, evidence-based guidelines such as those of the National Comprehensive Cancer Network, as well as additional emerging QIs for processes involving rapidly emerging technology. They specifically defined the QIs as clinical performance measures. Published results of the national survey database for patients treated in 1998 and 1999 were reviewed and additional analyses conducted to assess data adequacy to measure compliance with these clinical performance measures. Results: Examples of workup QIs for breast cancer patients showed that 97% underwent diagnostic bilateral mammography, 96% underwent pathology reviews, 83% underwent the determination of estrogen receptor status, 81% underwent the determination of progesterone receptor status, and 31% underwent the determination of human epidermal growth factor receptor 2 status. Compliance with treatment QIs for field recommendations on the basis of nodal findings can be measured. Of patients with prostate cancer, 90% underwent digital rectal examinations, 99% underwent prostate-specific antigen tests, and 99% had their Gleason scores determined. Compliance with QIs on the basis of prognostic group can also be measured. Conclusions: Benchmarking utilization patterns provides a foundation for assessing the appropriateness of cancer care in the future. The QRRO database is a rich data source, and the new survey will provide contemporary benchmark data for these measures. [Copyright &y& Elsevier]

Purpose: To investigate whether helical tomotherapy can provide conformal, uniform target-dose coverage for partial-breast irradiation (PBI) of patients positioned prone while achieving organ-at-risk sparing compliant with National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 guidelines; and to report our initial experience with the delivery of prone-breast PBI treatments using tomotherapy. Methods and Materials: For our pilot study, we generated helical tomotherapy plans upon the images of 10 prone-positioned patients previously treated using conventional techniques. We also generated plans for 4 left-breast prone-positioned PBI patients who were treated using helical tomotherapy, and recalculated the planned sinograms upon the pretreatment megavoltage computed tomographic images. Of the planning target volume (PTV), 95% was prescribed to receive 38.5 Gy, administered twice daily for 5 days. Results: For our pilot study, on average the maximum point dose to the PTV was 41.3 Gy, and 99% or more of the PTV received 90% or more of the prescribed dose. RTOG 0413 dose–volume histogram objectives were fulfilled for all organs at risk except the contralateral breast, which received a maximum point dose as high as 3.2 Gy in 1 case. For the prospective prone-positioned tomotherapy PBI plans, all objectives were met except the contralateral-breast maximum dose, which was 3.7 Gy on average. Dose calculation using the planned sinogram upon the pretreatment megavoltage computed tomographic images indicated consistency with the planned dose distributions. Conclusions: Helical tomotherapy can provide conformal and uniform target-dose coverage simultaneous with adequate sparing of critical structures; in this study only the contralateral breast dose exceeded RTOG 0413 guidelines. Dosimetric results for our 4 prospective patient cases were consistent with those for our 10-case pilot study. [Copyright &y& Elsevier]

Background: During the past 2 decades, breast conservation therapy (BCT) has become firmly established as a standard therapeutic approach for eligible women with early-stage breast cancer. Breast radiation after conservative surgery is an integral component of BCT, resulting in comparable local control and equivalent survival to mastectomy. Successful breast conservation relies on understanding key elements for patient selection, evaluation, treatment contraindications, radiation therapy methods, and integration with systemic therapy. Methods: The Appropriateness Criteria Committee of the American College of Radiology convened an expert panel to examine BCT for early-stage breast cancer. By using a modified Delphi technique to generate consensus, the expert panel responded to questionnaires on 9 clinical cases that address various key elements of breast conservation. A literature review on BCT led to the generation of an evidence table to support the consensus and overview. Results: Consensus for appropriateness criteria for BCT was produced for various clinical scenarios commonly encountered in practice. These topics include radiation oncology management issues related to young patient age, sentinel node biopsy, elderly patients, other histology, positive margins, extensive intraductal component, node-positive breast cancer, genetic breast cancer, partial breast irradiation, and systemic therapy. Radiation methods for BCT are reviewed. Conclusion: The Breast Cancer Panel has generated a consensus of up-to-date guidelines for the appropriate use of radiation for BCT by using a modified Delphi process for the American College of Radiology Appropriateness Criteria. [Copyright &y& Elsevier]

Purpose: The Patterns of Care Study performed this first known practice survey to establish a national profile of the delivery of postmastectomy radiotherapy (RT) in operable breast cancer.Methods and materials: A Patterns of Care Study research associate collected data from 55 randomly selected institutions. The survey data included 132 items describing the patient, pathologic features, and treatment course for patients with clinical Stage I, II, and IIIA breast cancer undergoing postmastectomy RT in 1998 and 1999. A multivariate analysis was performed to determine the impact of tumor factors and type of treatment facility on the radiation fields used.Results: A weighted sample size of 13,720 was obtained from a sampling of 405 patient records. The mean tumor size was 3.5 cm, and the mean number of axillary nodal metastases was 4.55. Lymphatic vascular invasion was noted in 34%, microscopic skin or dermal lymphatic invasion in 16%, positive or close margins in 36%, and extracapsular nodal extension in 23%. Radiotherapy included the chest wall in all cases and the regional nodes in 78%. When nodal RT was delivered, it included a supraclavicular field, supplemental axillary field, and/or an internal mammary field in 98%, 46%, and 23% of cases, respectively. Chest wall and supraclavicular RT was delivered in >90% of instances with 6-MV photons to doses between 45 and 50 Gy. More variation was seen in the delivery of the axillary and internal mammary RT. On multivariate analysis, the presence of four or more positive nodes and treatment at a large-volume facility were the factors most frequently associated with the use of regional radiation fields.Conclusion: This Patterns of Care Study survey has demonstrated that breast cancer patients undergoing postmastectomy RT in 1998 and 1999 had a high proportion of factors associated with an increased risk of locoregional failure. The practice patterns established in this study provide a baseline for comparison with future survey results. [Copyright &y& Elsevier]

Examines the theoretical capacity of G-protein-coupled receptors (GPCR) to interact with a wide range of proteins. GPCR structure; Interactions between GPCR and ion channels; GPCR signalling, internalization and desensitization.

Breast cancer–related lymphedema (BCRL) is a treatment complication that significantly reduces patient quality of life. Regional nodal irradiation (RNI) may increase the risk of BCRL. Recently, a region of the axilla known as the axillary-lateral thoracic vessel juncture (ALTJ) was identified as a potential organ at risk (OAR). Here, we set out to validate whether radiation dose to the ALTJ is associated with BCRL. We identified patients with stage II-III breast cancer treated with adjuvant RNI from 2013 to 2018, excluding those with BCRL preradiation. We defined BCRL as difference in arm circumference between the ipsilateral and contralateral limb >2.5 cm at any 1 encounter or ≥2 cm on ≥2 visits. All patients suspected of having BCRL at routine follow-up visits were referred to physical therapy for confirmation. The ALTJ was retrospectively contoured and dose metrics were collected. Cox proportional hazards regression models were used to test the association between clinical and dosimetric parameters with the development of BCRL. The study population included 378 patients with a median age of 53 years, median body mass index of 28.4 kg/m2, and median of 18 axillary nodes removed; 71% underwent mastectomy. Median follow-up was 70 months (interquartile range, 55-89.7 months). BCRL developed in 101 patients at a median of 18.9 months (interquartile range, 9.9-32.4 months), with a corresponding 5-year cumulative incidence BCRL of 25.8%. On multivariate analysis, none of the ALTJ metrics were associated with BCRL risk. Only increasing age, increasing body mass index, and increasing number of nodes were associated with a higher risk of developing BCRL. The 6-year locoregional recurrence rate was 3.2%, the axillary recurrence rate was 1.7%, and the isolated axillary recurrence rate was 0%. The ALTJ is not validated as a critical OAR for reducing BCRL risk. Until such an OAR is discovered, the axillary PTV should not be modified or dose reduced in efforts to reduce BCRL. [ABSTRACT FROM AUTHOR]

Introduction In 2014, the NRG Oncology Group initiated the first National Cancer Institute-sponsored, phase 1 clinical trial of stereotactic body radiation therapy (SBRT) for the treatment of multiple metastases in multiple organ sites (BR001; NCT02206334). The primary endpoint is to test the safety of SBRT for the treatment of 2 to 4 multiple lesions in several anatomic sites in a multi-institutional setting. Because of the technical challenges inherent to treating multiple lesions as their spatial separation decreases, we present the technical requirements for NRG-BR001 and the rationale for their selection. Methods and materials Patients with controlled primary tumors of breast, non-small cell lung, or prostate are eligible if they have 2 to 4 metastases distributed among 7 extracranial anatomic locations throughout the body. Prescription and organ-at-risk doses were determined by expert consensus. Credentialing requirements include (1) irradiation of the Imaging and Radiation Oncology Core phantom with SBRT, (2) submitting image guided radiation therapy case studies, and (3) planning the benchmark. Guidelines for navigating challenging planning cases including assessing composite dose are discussed. Results Dosimetric planning to multiple lesions receiving differing doses (45-50 Gy) and fractionation (3-5) while irradiating the same organs at risk is discussed, particularly for metastases in close proximity (≤ 5 cm). The benchmark case was selected to demonstrate the planning tradeoffs required to satisfy protocol requirements for 2 nearby lesions. Examples of passing benchmark plans exhibited a large variability in plan conformity. Discussion NRG-BR001 was developed using expert consensus on multiple issues from the dose fractionation regimen to the minimum image guided radiation therapy guidelines. Credentialing was tied to the task rather than the anatomic site to reduce its burden. Every effort was made to include a variety of delivery methods to reflect current SBRT technology. Although some simplifications were adopted, the successful completion of this trial will inform future designs of both national and institutional trials and would allow immediate clinical adoption of SBRT trials for oligometastases. [ABSTRACT FROM AUTHOR]

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]

Abstract: Background and purpose: To demonstrate and examine the ability of a newly developed software tool to estimate and analyze consensus contours from manually created contours by expert radiation oncologists. Material and methods: Several statistical methods and a graphical user interface were developed. For evaluation purposes, we used three breast cancer CT scans from the RTOG Breast Cancer Atlas Project. Specific structures were contoured before and after the experts’ consensus panel meeting. Differences in the contours were evaluated qualitatively and quantitatively by the consensus software tool. Estimates of consensus contours were analyzed for the different structures and Dice-similarity and Dice-Jaccard coefficients were used for comparative evaluation. Results: Based on kappa statistics, highest levels of agreement were seen in the left-breast, lumpectomy, and heart. Significant improvements between pre- and post-consensus contours were seen in delineation of the chestwall and breasts while significant variations were noticed in the supraclavicular and internal mammary nodes. Dice calculations for all pre-consensus STAPLE estimations and final consensus panel structures reached 0.80 or greater for the heart, left/right-breast, case-A lumpectomy, and chestwall. Conclusions: Using the consensus software tool incorporating STAPLE estimates provided the ability to create contours similar to the ones generated by expert physicians. [Copyright &y& Elsevier]

Purpose: Intra- and interfractional errors for breast cancer patients undergoing breast irradiation in the prone position were analyzed. Methods and Materials: To assess intrafractional error resulting from respiratory motion, four-dimensional computed tomography scans were acquired for 3 prone and 3 supine patients, and the respiratory motion was compared for the two positions. To assess the interfractional error caused by daily set-up variations, daily electronic portal images of one of the treatment beams were taken for 15 prone-positioned patients. Portal images were then overlaid with images from the planning system that included the breast contour and the isocenter, treatment beam portal, and isocenter. The shift between the planned and actual isocenter was recorded for each portal image, and descriptive statistics were collected for each patient. The margins were calculated using the 2Sigma + 0.7sigma recipe, as well as 95% confidence interval based on the pooled standard deviation of the datasets. Results: Respiratory motion of the chest wall is drastically reduced from 2.3 +/- 0.9 mm in supine position to -0.1 +/- 0.4 mm in prone position. The daily set-up errors vary in magnitude from 0.0 cm to 1.65 cm and are patient dependent. The margins were defined by considering only the standard deviation to be 1.1 cm, and 2.0 cm when the systematic errors were considered using the 2Sigma + 0.7sigma recipe. Conclusions: Prone positioning of patients for breast irradiation significantly reduces the uncertainty introduced by intrafractional respiratory motion. The presence of large systematic error in the interfractional variations necessitates a large clinical target volume-to-planning target volume margin and indicates the importance of image guidance for partial breast irradiation in the prone position, particularly using imaging modality capable of identifying the lumpectomy cavity. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Accelerated partial breast irradiation (APBI) is being studied in a phase III randomized trial as an alternative to whole breast irradiation (WBI) for early stage breast cancer patients. There are three methods for APBI: multi-catheter brachytherapy (MCT), MammoSite® brachytherapy (MST), or 3D conformal (3DCRT). There is a paucity of data comparing among methods. Using a linear–quadratic (LQ) model, we evaluated the anticipated efficacy among the APBI methods for equivalent uniform dose (EUD), Tumor Control Probability (TCP), and Normal Tissue Complication Probability (NTCP). Materials and methods: Treatment plans from five patients treated by each APBI modality were retrospectively selected. Dose-volume-histograms (DVH) for planning target volume (PTV), breast, and lung were generated. The LQ parameters α =0.3Gy−1 and α/β =10Gy were used for calculations. The values of EUD, TCP, and NTCP were calculated based on DVHs. Results: The average EUD (normalized to 3.4Gy BID) for the MCT, MST, and 3DCRT APBI was 35, 37.2, and 37.6Gy. When normalized to 2Gy fractionation these become, 42.2, 46.4, and 46.9Gy. Average TCP for MCT, MST, and 3DCRT PBI was 94.8%, 99.1%, and 99.2%. The NTCP values for breast and lung were low for all three methods. Conclusions: The EUD for PTV and TCP were most similar in MST and 3DCRT APBI and were lower in MCT APBI. This questions the equivalence of the three APBI modalities that are currently being evaluated in the NSABP-B39/RTOG 0413 protocol. [Copyright &y& Elsevier]

Purpose: The Patterns of Care Study survey process evaluation has been an effective means of assessing the evaluation and treatment practices used by radiation oncologists in the United States for Stage I-II breast cancer. The current 1998¿1999 report updates the previous 1989 and 1993¿1994 analyses and reflects the recent changes in surgery and systemic therapy observed nationally in the management of early-stage disease. Methods and Materials: A weighted sample size of 71,877 patient records of women treated with breast-conserving surgery and radiotherapy (RT) was obtained from a stratified two-stage sampling of 353 patient records. These cases were centrally reviewed from academic and private radiation oncology practices across the United States. The data collected included patient characteristics, clinical and pathologic factors, and surgical and RT details. The results were compared with those of previous Patterns of Care Study survey reports. Results: Of the patients in the current survey, 97% had undergone mammography before biopsy. A review of the primary tumor pathologic findings indicated improved quantification of an intraductal component from 7.0% in 1993¿1994 to 20.4% in 1998¿1999 (p = 0.01). The tumor characteristics were better defined, with estrogen and progesterone receptor measurement performed in 91.4% and 91.3% in the 1998¿1999 survey vs. 83.7% and 80.3% in the 1989 survey, respectively (p = 0.03 and p = 0.002, respectively). Axillary dissection was performed in 82.2% in the present survey compared with 93.6% in the 1993¿1994 survey (p = 0.0004); sentinel node biopsy was performed in 20.1% of the present cases. The use of CT for planning was increased in the current survey, with 22.9% cases CT planned vs. 9% in 1993¿1994 (p = 0.10). In the present survey, 100% had received whole breast RT. When a supraclavicular field was added, the dose was prescribed to a specified depth in 67.5% of cases, most commonly 3 cm. When an axillary field was added, the dose was generally prescribed to the mid-plane. Chemotherapy and tamoxifen was used in 36% and 55.8% of patients, respectively, in the 1998¿1999 survey, representing a statistically significant increase compared with the 1993¿1994 survey, despite comparable pathologic tumor size and nodal involvement. Conclusion: The present results demonstrate a high level of compliance of the sampled radiation oncology practices with current breast conservation standards and continued improvement in many categories compared with prior patterns of care study surveys. The estimates in the current survey after whole breast RT will serve as a benchmark against newer trends in breast cancer RT, such as partial breast RT. [Copyright &y& Elsevier]

GABAB receptors have been implicated in the GABAergic modulation of catecholaminergic and serotonergic pathways in the central nervous system. The GABAB receptor may require two subunits, GABABR1 and GABABR2, for functional activity. Using dual immunofluorescent labelling on adjacent cryostat sections, we investigated the presence of immunoreactivity for the GABABR1 and GABABR2 subunits in brainstem catecholamine (tyrosine hydroxylase-immunoreactive) and serotonin (tryptophan hydroxylase-immunoreactive) neurons. All neurons (>98%) examined in catecholamine groups A1, A2, A5, A6, C1, and serotonin groups B1–3 and B6–8 were immunoreactive for the GABABR1 subunit. All A5 and A6 neurons (>97%) and at least 86% of A1, A2, C1, B2, B3, B7 and B8 neurons examined were GABABR2-immunoreactive. The proportion of neurons with immunoreactivity for the GABABR2 subunit varied between 0% and 99% for B1 neurons, and between 35% and 93% for B6 neurons. Statistical analysis showed that similar proportions of sampled neurons were immunoreactive for GABABR1 and GABABR2 in the A1, A5, A6, C1, B2 and B7 cell groups, whereas a smaller proportion of A2, B1, B3, B6 and B8 neurons were GABABR2-immunoreactive than GABABR1-immunoreactive. In general, our results suggest that GABABR1 and GABABR2 co-exist in the great majority of brainstem catecholamine and serotonin neurons. In the neurons that lack GABABR2, the GABABR1 subunit may act alone or with another protein. [Copyright &y& Elsevier]

• We found that >15% of RNI patients developed symptomatic esophagitis. • IMRT use was associated with higher rates of esophagitis. • The esophagus OAR was systematically contoured from cricoid to carina. • We propose these esophageal OAR constraints: mean <11 Gy, V10 <30%, and V20 <15%. Rates of acute esophagitis in breast cancer patients undergoing regional nodal irradiation (RNI) are under-reported. We set to identify esophageal dose–volume constraints associated with grade 2 esophagitis (G2E). We hypothesized that the G2E rate was higher with intensity modulated radiation therapy (IMRT) vs. 3D conformal radiation therapy (3DCRT). We identified patients that received RNI (50 Gy/25 fractions) from 1/2013 to 6/2019. We retrospectively contoured the esophagus in a consistent manner and recorded esophageal mean dose, max dose, and V10–V50. Our primary endpoint was the G2E rate. Receiver operating characteristics curves analysis (e.g., Youden's J statistic) were used to determine the cutpoints for the dosimetric parameters which were then tested in logistic regression models. We identified 531 patients (50% left-sided; 41% IMRT; 16.2% G2E). G2E was significantly higher in IMRT vs. 3DCRT patients (23.6% vs. 10.9%, p < 0.0001). All esophageal dosimetric parameters were significantly associated with G2E after adjusting for age and laterality. The cutpoints for esophageal mean dose, V10 and V20 were 11 Gy, 30%, and 15%, respectively. The associations between the dichotomized dose–volume parameters and G2E were OR = 3.82 (95% CI 2.28–6.40, p < 0.0001) for esophageal mean dose, OR = 5.37 (95% CI 3.01–9.58, p < 0.0001) for esophageal V10, and OR = 3.23 (95% CI 1.93–5.41, p < 0.0001) for esophageal V20. In patients receiving RNI with modern techniques, we found that G2E occurs in >15%, and more frequently with IMRT. These data strongly support the routine contouring of the esophagus in RNI planning, and our constraints should be incorporated in future prospective protocols of RNI. [ABSTRACT FROM AUTHOR]

Purpose: Clinical trials support adjuvant regional nodal irradiation (RNI) after breast-conserving surgery or mastectomy for patients with lymph node-positive breast cancer. Advanced treatment planning techniques (eg, intensity modulated radiation therapy [IMRT]) can reduce dose to organs at risk (OARs) in this situation. However, uncertainty persists about when IMRT is clinically indicated (vs 3-dimensional conformal radiation therapy [3DCRT]) for RNI. We hypothesized that an adaptive treatment planning algorithm (TPA) for IMRT adoption would allow OAR constraints for RNI to be met when 3DCRT could not without significantly changing toxicity and locoregional recurrence (LRR) patterns.Methods and Materials: Since 2013, all RNI patients also underwent an adaptive TPA that began with 3DCRT and then changed to IMRT when OAR constraints (mean heart dose ≤500 cGy; ipsilateral lung V20 ≤35%) could not be met. Patients received 2 Gy/d to the prospectively contoured target volumes (including internal mammary nodes). We retrospectively evaluated the dosimetry and clinical outcomes of the treatment groups (IMRT vs 3DCRT). The primary endpoint was the cumulative incidence of LRR as the site of first recurrence, and we specifically address patterns of failure based on dose to the posterior supraclavicular nodal region (SCL-post).Results: Two hundred forty patients (60% stage III; mean 4.0 + nodes) underwent an adaptive-TPA for RNI after mastectomy (74%) or breast-conserving surgery (26%), resulting in 168 patients treated with 3DCRT and 72 patients treated with IMRT. There were 7 LRRs (2 IMRT, 5 3DCRT) resulting in 4-year LRR of 2.8% for IMRT versus 1.8% for 3DCRT (P = .99). Three patients (2 IMRT, 1 3DCRT) had SCL nodal failures (1 in the SCL-post).Conclusions: An adaptive TPA for use of IMRT when 3DCRT does not meet critical OAR constraints resulted in rare high-grade toxicity and no difference in failure patterns between patients treated with IMRT and 3DCRT. These data should provide reassurance that IMRT maintains the therapeutic ratio by preserving cancer control outcomes without excess toxicity when 3DCRT fails to meet OAR constraints. [ABSTRACT FROM AUTHOR]

Purpose: To determine the associated toxicity, tolerance, and safety of partial-breast reirradiation.Methods and Materials: Eligibility criteria included in-breast recurrence occurring >1 year after whole-breast irradiation, <3 cm, unifocal, and resected with negative margins. Partial-breast reirradiation was targeted to the surgical cavity plus 1.5 cm; a prescription dose of 45 Gy in 1.5 Gy twice daily for 30 treatments was used. The primary objective was to evaluate the rate of grade ≥3 treatment-related skin, fibrosis, and/or breast pain adverse events (AEs), occurring ≤1 year from re-treatment completion. A rate of ≥13% for these AEs in a cohort of 55 patients was determined to be unacceptable (86% power, 1-sided α = 0.07).Results: Between 2010 and 2013, 65 patients were accrued, and the first 55 eligible and with 1 year follow-up were analyzed. Median age was 68 years. Twenty-two patients had ductal carcinoma in situ, and 33 had invasive disease: 19 ≤1 cm, 13 >1 to ≤2 cm, and 1 >2 cm. All patients were clinically node negative. Systemic therapy was delivered in 51%. All treatment plans underwent quality review for contouring accuracy and dosimetric compliance. All treatment plans scored acceptable for tumor volume contouring and tumor volume dose-volume analysis. Only 4 (7%) scored unacceptable for organs at risk contouring and organs at risk dose-volume analysis. Treatment-related skin, fibrosis, and/or breast pain AEs were recorded as grade 1 in 64% and grade 2 in 7%, with only 1 (<2%) grade ≥3 and identified as grade 3 fibrosis of deep connective tissue.Conclusion: Partial-breast reirradiation with 3-dimensional conformal radiation therapy after second lumpectomy for patients experiencing in-breast failures after whole-breast irradiation is safe and feasible, with acceptable treatment quality achieved. Skin, fibrosis, and breast pain toxicity was acceptable, and grade 3 toxicity was rare. [ABSTRACT FROM AUTHOR]

Purpose: The NRG-BR001 trial is the first National Cancer Institute-sponsored trial to treat multiple (range 2-4) extracranial metastases with stereotactic body radiation therapy. Benchmark credentialing is required to ensure adherence to this complex protocol, in particular, for metastases in close proximity. The present report summarizes the dosimetric results and approval rates.Methods and Materials: The benchmark used anonymized data from a patient with bilateral adrenal metastases, separated by <5 cm of normal tissue. Because the planning target volume (PTV) overlaps with organs at risk (OARs), institutions must use the planning priority guidelines to balance PTV coverage (45 Gy in 3 fractions) against OAR sparing. Submitted plans were processed by the Imaging and Radiation Oncology Core and assessed by the protocol co-chairs by comparing the doses to targets, OARs, and conformity metrics using nonparametric tests.Results: Of 63 benchmarks submitted through October 2015, 94% were approved, with 51% approved at the first attempt. Most used volumetric arc therapy (VMAT) (78%), a single plan for both PTVs (90%), and prioritized the PTV over the stomach (75%). The median dose to 95% of the volume was 44.8 ± 1.0 Gy and 44.9 ± 1.0 Gy for the right and left PTV, respectively. The median dose to 0.03 cm3 was 14.2 ± 2.2 Gy to the spinal cord and 46.5 ± 3.1 Gy to the stomach. Plans that spared the stomach significantly reduced the dose to the left PTV and stomach. Conformity metrics were significantly better for single plans that simultaneously treated both PTVs with VMAT, intensity modulated radiation therapy, or 3-dimensional conformal radiation therapy compared with separate plans. No significant differences existed in the dose at 2 cm from the PTVs.Conclusions: Although most plans used VMAT, the range of conformity and dose falloff was large. The decision to prioritize either OARs or PTV coverage varied considerably, suggesting that the toxicity outcomes in the trial could be affected. Several benchmarks met the dose-volume histogram metrics but produced unacceptable plans owing to low conformity. Dissemination of a frequently-asked-questions document improved the approval rate at the first attempt. Benchmark credentialing was found to be a valuable tool for educating institutions about the protocol requirements. [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]

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: 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]

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: To investigate respiration-induced heart motion for left-sided breast irradiation using a four-dimensional computed tomography (4DCT) technique and to determine novel indications to assess heart motion and identify breast patients who may benefit from a gated treatment. Methods and Materials: Images of 4DCT acquired during free breathing for 20 left-sided breast cancer patients, who underwent whole breast irradiation with or without regional nodal irradiation, were analyzed retrospectively. Dose distributions were reconstructed in the phases of 0%, 20%, and 50%. The intrafractional heart displacement was measured in three selected transverse CT slices using DLAD (the distance from left ascending aorta to a fixed line [connecting middle point of sternum and the body] drawn on each slice) and maximum heart depth (MHD, the distance of the forefront of the heart to the line). Linear regression analysis was used to correlate these indices with mean heart dose and heart dose volume at different breathing phases. Results: Respiration-induced heart displacement resulted in observable variations in dose delivered to the heart. During a normal free-breathing cycle, heart-induced motion DLAD and MHD changed up to 9 and 11 mm respectively, resulting in up to 38% and 39% increases of mean doses and V25.2 for the heart. MHD and DLAD were positively correlated with mean heart dose and heart dose volume. Respiratory-adapted gated treatment may better spare heart and ipsilateral-lung compared with the conventional non-gated plan in a subset of patients with large DLAD or MHD variations. Conclusion: Proposed indices offer novel assessment of heart displacement based on 4DCT images. MHD and DLAD can be used independently or jointly as selection criteria for respiratory gating procedure before treatment planning. Patients with great intrafractional MHD variations or tumor(s) close to the diaphragm may particularly benefit from the gated treatment. [ABSTRACT FROM AUTHOR]

Purpose: In this work, we quantify the interfractional variations in the shape of the clinical target volume (CTV) by analyzing the daily CT data acquired during CT-guided partial breast irradiation (PBI) and compare the effectiveness of various repositioning alignment strategies considered to account for the variations. Methods and Materials: The daily CT data for 13 breast cancer patients treated with PBI in either prone (10 patients) or supine (3 patients) with daily kV CT guidance using CT on Rails (CTVision, Siemens, Malvern, PA) were analyzed. For approximately 25 points on the surface of the CTV, deformation vectors were calculated by means of deformable image registration and verified by visual inspection. These were used to calculate the distances along surface normals (DSN), which directly related to the required margin expansions for each point. The DSN values were determined for seven alignment methods based on volumetric imaging and also two-dimensional projections (portal imaging). Results: The margin expansion necessary to cover 99% of all points for all days was 2.7 mm when utilizing the alignment method based on deformation field data (the best alignment method). The center-of-mass based alignment yielded slightly worse results (a margin of 4.0 mm), and shifts obtained by operator placement (7.9 mm), two-dimensional-based methods (7.0–10.1 mm), and skin marks (13.9 mm) required even larger margin expansions. Target shrinkage was evident for most days by the negative values of DSN. Even with the best alignment, the range of DSN values could be as high as 7 mm, resulting in a large amount of normal tissue irradiation, unless adaptive replanning is employed. Conclusion: The appropriate alignment method is important to minimize the margin requirement to cover the significant interfractional target deformations observed during PBI. The amount of normal tissue unnecessarily irradiated is still not insignificant, and can be minimized if adaptive radiotherapy is applied. [ABSTRACT FROM AUTHOR]