Breast Neoplasms: Arthur DW

Smith BD, Arthur DW, Buchholz TA, Haffty BG, Hahn CA, Hardenbergh PH, Julian TB, Marks LB, Todor DA, Vicini FA, Whelan TJ, White J, Wo JY, Harris JR. · Radiation Oncology Flight, Wilford Hall Medical Center, Lackland AFB, TX, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #19545784 No free full text.

Abstract: 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.

Taylor ME, Haffty BG, Rabinovitch R, Arthur DW, Halberg FE, Strom EA, White JR, Cobleigh MA, Edge SB. · Washington University, Saint Louis, Missouri 63110-1032, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #19251087 No free full text.

Abstract: 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.

Arthur DW, Vicini FA, Kuske RR, Wazer DE, Nag S, Anonymous00286. · Virginia Commonwealth University, Medical College of Virginia Campus, Richmond 23298-0058, USA. · Brachytherapy. · Pubmed #15062164 No free full text.

Abstract: Logistical barriers of time and travel created by the conventional six week course of radiotherapy prevent many women from pursuing breast conservation treatment. For the past 12 years, Accelerated Partial Breast Irradiation (APBI) has been investigated as a potential alternative treatment approach in women with early stage breast cancer. The ability to complete treatment in five days has the potential to provide additional women with the option of breast conservation. The validity of this APBI is supported in the study of in-breast recurrence patterns, pathologic data and the clinical treatment experience. The review of the recent data on contemporary APBI reveals that patient selection criteria and brachytherapy quality assurance are clearly critical components and necessary to assure a successful treatment outcome. This updated report from the American Brachytherapy Society on Accelerated Partial Breast Irradiation reviews the appropriate background data supporting this treatment approach with conclusions regarding patient selection criteria and treatment delivery.

Arthur DW, Vicini FA, Kuske RR, Wazer DE, Nag S, Anonymous00345. · Department of Radiation Oncology, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond 23298-0058, USA. · Brachytherapy. · Pubmed #15062155 No free full text.

Abstract: Logistical barriers of time and travel created by the conventional six-week course of radiotherapy prevent many women from pursuing breast conservation treatment. For the past 12 years, Accelerated Partial Breast Irradiation (APBI) has been investigated as a potential alternative treatment approach in women with early stage breast cancer. The ability to complete treatment in five days has the potential to provide additional women with the option of breast conservation. The validity of this APBI is supported in the study of in-breast recurrence patterns, pathologic data and the clinical treatment experience. The review of the recent data on contemporary APBI reveals that patient selection criteria and brachytherapy quality assurance are clearly critical components and necessary to assure a successful treatment outcome. This updated report from the American Brachytherapy Society on Accelerated Partial Breast Irradiation reviews the appropriate background data supporting this treatment approach with conclusions regarding patient selection criteria and treatment delivery.

Arthur DW, Vicini FA. · No affiliation provided · Ann Surg Oncol. · Pubmed #15249340 No free full text.

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Keisch M, Arthur DW. · Department of Radiation Oncology, Mount Sinai Comprehensive Cancer Center, Miami Beach, FL 33140, USA. · Brachytherapy. · Pubmed #16182215 No free full text.

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Vicini FA, Arthur DW. · Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073-6769, USA. · Semin Radiat Oncol. · Pubmed #15809936 No free full text.

Abstract: Accelerated partial breast irradiation (APBI) has been investigated for over a decade as a potential alternative adjuvant treatment approach after lumpectomy for women with early-stage breast cancer. The rationale for APBI is based on pathologic data regarding the spread of cancer within the breast and study of the patterns of in-breast recurrence after breast-conserving therapy performed with or without whole-breast irradiation. This report reviews the North American experience using interstitial brachytherapy for APBI. Studies achieving low failure rates have universally been distinguished from those with high failure rates by requiring documented microscopically negative surgical margins, using a target definition consisting of the lumpectomy cavity plus a 1- to 2-cm margin, and having a rigorous quality assurance program to assure target coverage. We conclude that APBI brachytherapy programs that include all of these components have great potential to overcome many of the barriers that have prevented women from pursuing standard breast-conserving therapy.

Arthur DW, Vicini FA. · Radiation Oncology Department, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA, USA. · J Clin Oncol. · Pubmed #15755981 No free full text.

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Arthur DW, Morris MM, Vicini FA. · Department of Radiation Oncology, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, Virginia, USA. · Oncology (Williston Park). · Pubmed #15648295 No free full text.

Abstract: Conventional radiotherapeutic treatment for early and advanced breast cancer has been based on broad-field radiation treatment principles that date back several decades. Although these strategies have been successful, newer techniques now offer the ability to incorporate improved target imaging, dosimetric planning, and treatment delivery into the treatment design. These newer techniques include accelerated partial-breast irradiation and hypofractionated whole-breast irradiation for early-stage breast cancer, and intensity-modulated radiotherapy (IMRT) for both early and advanced breast cancer. Accelerated partial-breast irradiation and hypofractionated whole-breast radiotherapy are treatment approaches that promise both reduced overall treatment times and the potential for increased use of breast-conservation therapy. IMRT offers unparalleled dose homogeneity and conformality that enables dose reduction to normal structures with the potential to reduce treatment toxicity and improve cosmesis. Based on the published literature, an increasing number of treatment facilities are offering treatment with these techniques. However, further clinical study remains important to thoroughly define the appropriate clinical setting, patient selection criteria, and limitations for each of these innovative treatment approaches.

Kuerer HM, Arthur DW, Haffty BG. · Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. · Cancer. · Pubmed #15160329 links to  free full text

Abstract: Mastectomy is the current standard of care for in-breast local recurrence of breast carcinoma. The objective of the current study was to critically review the rationale for and the theoretic and actual risks and benefits of repeat breast-conserving surgery followed by partial breast irradiation (PBI) for in-breast local recurrence of breast carcinoma. The main outcomes of interest were local control and survival after in-breast local recurrence and side effects, complications, and cosmesis after reirradiation of the breast. The risk of local recurrence was not found to be eliminated with mastectomy; approximately 2-32% of patients treated with mastectomy develop a chest wall recurrence. The interpretation of local control rates in evaluating repeat breast-conserving surgery studies is difficult because of the lack of information regarding preoperative diagnostic mammography to rule out concurrent multicentric disease and microscopic margin status after surgery. Rates of subsequent local recurrence in these studies appeared to be between 19-50%, similar to reported rates of in-breast local recurrence in patients with a first diagnosis of breast carcinoma who were treated with conservative surgery without irradiation. Early follow-up studies of breast reirradiation suggest that catheter-based interstitial brachytherapy and standard external beam radiation therapy can be delivered to the breast more than once without significant side effects in most patients and with acceptable cosmesis in some patients. Mastectomy may not be necessary in all patients with an in-breast local recurrence of breast carcinoma. Recent advances in conformal radiation delivery and single-center published reports concerning repeat breast-conserving therapy support well designed prospective trials to formally test this hypothesis.

Nag S, Kuske RR, Vicini FA, Arthur DW, Zwicker RD. · James Cancer Hospital and Solove Research Institute, Ohio State University, Columbus, Ohio, USA. · Oncology (Williston Park). · Pubmed #11252933 No free full text.

Abstract: Whole-breast external-beam radiation therapy (EBRT) involves a 6-week course of fractionated treatments. In contrast, brachytherapy can be completed in a 4- to 5-day treatment course. Because of this shortened time frame, there has been interest in breast brachytherapy as a sole modality after lumpectomy. The American Brachytherapy Society (ABS) has issued guidelines specifically for the use of brachytherapy in breast carcinoma. In these guidelines, the ABS addresses important areas of controversy related to the indications, execution, and evaluation of breast implants when utilized in the following settings: as the sole treatment modality following lumpectomy, as an alternative to a 6-week course of EBRT following lumpectomy, as a boost following whole-breast irradiation, and for the treatment of local recurrences following breast-conservation treatment. The ABS recommends a precise definition and meticulous delineation of the clinical target volume. In addition, the Society recommends the routine use of dose-volume histograms and a dose-homogeneity index as tools to ensure reproducible brachytherapy and to allow interinstitutional comparisons. Brachytherapy as a sole modality is currently considered investigational and should be performed in the context of a controlled clinical trial. Practitioners and cooperative groups are encouraged to use these guidelines to formulate treatment and dose-reporting policies, but responsibility for medical decisions ultimately rests with the treating radiation oncologist.

Arthur DW, Winter K, Kuske RR, Bolton J, Rabinovitch R, White J, Hanson WF, Wilenzick RM, McCormick B. · Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA 23298-0058, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18294778 No free full text.

Abstract: PURPOSE: Radiation Therapy Oncology Group 95-17 is a prospective Phase II cooperative group trial of accelerated partial breast irradiation (APBI) alone using multicatheter brachytherapy after lumpectomy in select early-stage breast cancers. Tumor control and survival outcomes are reported. METHODS AND MATERIALS: Eligibility criteria included Stage I/II breast carcinoma confirmed to be <3 cm, unifocal, invasive nonlobular histology with zero to three positive axillary nodes without extracapsular extension. APBI treatment was delivered with either low-dose-rate (LDR) (45 Gy in 3.5-5 days) or high-dose-rate (HDR) brachytherapy (34 Gy in 10 twice-daily fractions over 5 days). End points evaluated included in-breast control, regional control, mastectomy-free rate, mastectomy-free survival, disease-free survival, and overall survival. The study was designed to analyze the HDR and LDR groups separately and without comparison. RESULTS: Between 1997 and 2000, 100 patients were accrued and 99 were eligible; 66 treated with HDR brachytherapy and 33 treated with LDR brachytherapy. Eighty-seven patients had T1 lesions and 12 had T2 lesions. Seventy-nine were pathologically N0 and 20 were N1. Median follow-up in the HDR group is 6.14 years with the 5-year estimates of in-breast, regional, and contralateral failure rates of 3%, 5%, and 2%, respectively. The LDR group experienced similar results with a median follow-up of 6.22 years. The 5-year estimates of in-breast, regional, and contralateral failure rates of 6%, 0%, and 6%, respectively. CONCLUSION: Patients treated with multicatheter partial breast brachytherapy in this trial experienced excellent in-breast control rates and overall outcome that compare with reports from APBI studies with similar extended follow-up.

Kuske RR, Winter K, Arthur DW, Bolton J, Rabinovitch R, White J, Hanson W, Wilenzick RM. · Arizona Oncology Services and Foundation for Cancer Research and Education, Phoenix, AZ 85013, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #16503383 No free full text.

Abstract: PURPOSE: Accelerated partial breast irradiation (APBI) can be delivered with brachytherapy within 4-5 days compared with 5-6 weeks for conventional whole breast external beam radiotherapy. Radiation Therapy Oncology Group 95-17 is the first prospective phase I-II cooperative group trial of APBI alone after lumpectomy in select patients with breast cancer. The toxicity rates are reported for low-dose-rate (LDR) and high-dose-rate (HDR) APBI on this trial. METHODS AND MATERIALS: The inclusion criteria for this study included invasive nonlobular tumors < or =3 cm after lumpectomy with negative surgical margins and axillary dissection with zero to three positive axillary nodes without extracapsular extension. The patients were treated with either LDR APBI (45 Gy in 3.5-5 days) or HDR APBI (34 Gy in 10 twice-daily fractions within 5 days). Chemotherapy (> or =2 weeks after APBI) and/or tamoxifen could be given at the discretion of the treating physicians. RESULTS: Between August 1997 and March 2000, 100 women were enrolled in this study, and 99 were evaluated. Of the 99 women, 33 were treated with LDR and 66 with HDR APBI. The median follow-up for all patients was 2.7 years (range, 0.6-4.4 years) and was 2.9 years for LDR and 2.7 years for HDR patients. Toxicities attributed to APBI included erythema, edema, tenderness, pain, and infection. Of the 66 patients treated with HDR APBI, 2 (3%) had Grade 3 or 4 toxicity. Of the 33 patients treated with LDR, 3 (9%) had Grade 3 or 4 toxicity during brachytherapy. Late toxicities included skin thickening, fibrosis, breast tenderness, and telangiectasias. No patient experienced late Grade 4 toxicity; the rate of Grade 3 toxicity was 18% for the LDR and 4% for the HDR groups. CONCLUSION: Acute and late toxicity for this invasive breast radiation technique was modest and acceptable. Patients receiving chemotherapy, a nonprotocol therapy, had a greater rate of Grade 3 toxicity. The study design did not allow for this to be tested statistically.

George R, Keall PJ, Kini VR, Vedam SS, Siebers JV, Wu Q, Lauterbach MH, Arthur DW, Mohan R. · Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia 23298, USA. · Med Phys. · Pubmed #12722807 No free full text.

Abstract: Respiratory motion during intensity modulated radiation therapy (IMRT) causes two types of problems. First, the clinical target volume (CTV) to planning target volume (PTV) margin needed to account for respiratory motion means that the lung and heart dose is higher than would occur in the absence of such motion. Second, because respiratory motion is not synchronized with multileaf collimator (MLC) motion, the delivered dose is not the same as the planned dose. The aims of this work were to evaluate these problems to determine (a) the effects of respiratory motion and setup error during breast IMRT treatment planning, (b) the effects of the interplay between respiratory motion and multileaf collimator (MLC) motion during breast IMRT delivery, and (c) the potential benefits of breast IMRT using breath-hold, respiratory gated, and 4D techniques. Seven early stage breast cancer patient data sets were planned for IMRT delivered with a dynamic MLC (DMLC). For each patient case, eight IMRT plans with varying respiratory motion magnitudes and setup errors (and hence CTV to PTV margins) were created. The effects of respiratory motion and setup error on the treatment plan were determined by comparing the eight dose distributions. For each fraction of these plans, the effect of the interplay between respiratory motion and MLC motion during IMRT delivery was simulated by superimposing the respiratory trace on the planned DMLC leaf motion, facilitating comparisons between the planned and expected dose distributions. When considering respiratory motion in the CTV-PTV expansion during breast IMRT planning, our results show that PTV dose heterogeneity increases with respiratory motion. Lung and heart doses also increase with respiratory motion. Due to the interplay between respiratory motion and MLC motion during IMRT delivery, the planned and expected dose distributions differ. This difference increases with respiratory motion. The expected dose varies from fraction to fraction. However, for the seven patients studied and respiratory trace used, for no breathing, shallow breathing, and normal breathing, there were no statistically significant differences between the planned and expected dose distributions. Thus, for breast IMRT, intrafraction motion degrades treatment plans predominantly by the necessary addition of a larger CTV to PTV margin than would be required in the absence of such motion. This motion can be limited by breath-hold, respiratory gated, or 4D techniques.

Li XA, Tai A, Arthur DW, Buchholz TA, Macdonald S, Marks LB, Moran JM, Pierce LJ, Rabinovitch R, Taghian A, Vicini F, Woodward W, White JR, Anonymous00081. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #19215827 No free full text.

Abstract: 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.

Cuttino LW, Todor D, Rosu M, Arthur DW. · Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA, USA. · Brachytherapy. · Pubmed #19211310 No free full text.

Abstract: PURPOSE: Accelerated partial breast irradiation (APBI) continues to increase in popularity. Up to 14% of patients treated with the MammoSite (MS) report some degree of chronic pain, which may be related to chest wall toxicity. Reports from several institutions using the multicatheter (MC) technique have not shown associated elevated chest wall toxicity. Additionally, a recent investigation has suggested that increased toxicity may occur with the MS when the dose to the chest wall exceeds 125% of the prescribed dose. This investigation compares the skin and chest wall doses of a cohort of patients treated with the MC technique to a group treated with the MS. METHODS AND MATERIALS: The dosimetric data for 43 patients treated with the MC technique and 83 patients treated with the MS at Virginia Commonwealth University were reviewed. This cohort represents consecutively treated patients from our most recent experience to minimize any learning curve effect on dosimetry. Plans were generated using 3D software (Brachyvision, Varian Medical Systems, Inc., Palo Alto, CA). Multiple dwell positions were used for all MS patients to optimize dose delivery. The minimum distances from the planning target volume to the skin and chest wall were calculated, as well as the maximum doses delivered to the skin and chest wall. RESULTS: The mean skin distances for patients treated with the MC technique and the MS were 0.5 and 0.9cm, respectively (p<0.002). Despite the significantly smaller mean skin distance, the mean skin dose for the MC technique was only 2.3Gy per fraction (67% of prescription dose). The mean skin dose for the MS was 3.2Gy per fraction (94% of prescription dose, p<0.001). The mean chest wall distance was 0.9cm for the MC technique and 1.0cm for the MS (p=0.55). Again, the mean chest wall dose for the MC technique was only 2.3Gy per fraction (67% of prescription dose). The mean skin dose for the MS was 3.6Gy per fraction (105% of prescription dose, p<0.001). The percentage of patients receiving skin doses in excess of 125% for the MC and MS were 0% and 9.6%, respectively. The percentage of patients receiving chest wall doses in excess of 125% for the MC and MS were 0% and 38.6%, respectively. CONCLUSION: The MC technique results in more conformal dose delivery, with significantly lower mean skin and chest wall doses. Treatment with the MS was associated with significantly more patients receiving doses to the skin or chest wall in excess of 125% of the prescription. Given the limited followup available for the MS, and the significant dose delivered to the chest wall, the use of this device may be associated with a higher incidence of late chest wall toxicity than previously expected.

McIntosh A, Read PW, Khandelwal SR, Arthur DW, Turner AB, Ruchala KJ, Olivera GH, Jeswani S, Sheng K. · Department of Radiation Oncology, University of Virginia, Charlottesville, VA 22908, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18474316 No free full text.

Abstract: PURPOSE: To investigate the use of topotherapy for accelerated partial breast irradiation through field-design optimization and dosimetric comparison to linear accelerator-based three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: Hypothetical 3-cm lumpectomy sites were contoured in each quadrant of a left breast by using dosimetric guidelines from the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 protocol. Coplanar intensity-modulated topotherapy treatment plans were optimized by using two-, three-, four-, five-, and seven-field arrangements for delivery by the tomotherapy unit with fixed gantry angles. Optimized noncoplanar five-field 3D-CRT and IMRT were compared with corresponding topotherapy plans. RESULTS: On average, 99.5% +/- 0.5% of the target received 100% of the prescribed dose for all topotherapy plans. Average equivalent uniform doses ranged from 1.20-2.06, 0.79-1.76, and 0.10-0.29 Gy for heart, ipsilateral lung, and contralateral lung, respectively. Average volume of normal breast exceeding 90% of the prescription and average area of skin exceeding 35 Gy were lowest for five-field plans. Average uniformity indexes for five-field plans using 3D-CRT, IMRT, and topotherapy were 1.047, 1.050, and 1.040, respectively. Dose-volume histograms and calculated equivalent uniform doses of all three techniques illustrate clinically equivalent doses to ipsilateral breast, lung, and heart. CONCLUSIONS: This dosimetric evaluation for a single patient shows that coplanar partial breast topotherapy provides good target coverage with exceptionally low dose to organs at risk. Use of more than five fields provided no additional dosimetric advantage. A comparison of five-field topotherapy to 3D-CRT and IMRT for accelerated partial breast irradiation illustrates equivalent target conformality and uniformity.

Cuttino LW, Keisch M, Jenrette JM, Dragun AE, Prestidge BR, Quiet CA, Vicini FA, Rescigno J, Wazer DE, Kaufman SA, Ramakrishnan VR, Patel R, Arthur DW. · Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, VA 23298-0058, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18037585 No free full text.

Abstract: PURPOSE: To present a retrospective multi-institutional experience of patients treated with the MammoSite radiation therapy system (RTS). METHODS AND MATERIALS: Nine institutions participated in a pooled analysis of data evaluating the clinical experience of the MammoSite RTS for delivering accelerated partial breast irradiation. Between 2000 and 2004, 483 patients were treated with the MammoSite RTS to 34 Gy delivered in 10 fractions. Treatment parameters were analyzed to identify factors affecting outcome. RESULTS: Median follow-up was 24 months (minimum of 1 year). Overall, infection was documented in 9% of patients, but the rate was only 4.8% if the catheter was placed after lumpectomy. Six patients (1.2%) experienced an in-breast failure; four failures occurred remote from the lumpectomy site (elsewhere failure). Cosmetic results were good/excellent in 91% of patients. Treatment parameters identified as significant on univariate analysis were tested in multivariate regression analysis. The closed-cavity placement technique significantly reduced the risk of infection (p = 0.0267). A skin spacing of <6 mm increased the risk of severe acute skin reaction (p = 0.0178) and telangiectasia (p = 0.0280). The use of prophylactic antibiotics reduced the risk of severe acute skin reaction (p < 0.0001). The use of multiple dwell positions reduced the risk of severe hyperpigmentation (p = 0.0278). Infection was associated with an increased risk of fair or poor overall cosmesis (p = 0.0009). CONCLUSIONS: In this series of patients, the MammoSite RTS seems to have acceptable toxicity rates and cosmetic outcomes, comparable to those with whole-breast radiotherapy. On the basis of these data, the closed-cavity placement technique, use of prophylactic antibiotics, use of multiple dwell positions, and a minimum skin spacing of 6 mm seem to improve patient outcome.

Dogan N, Cuttino L, Lloyd R, Bump EA, Arthur DW. · Department of Radiation Oncology, Virginia Commonwealth University Medical Center, 401 College Street, Richmond, VA 23298, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #17512134 No free full text.

Abstract: PURPOSE: To determine whether the use of intensity-modulated radiotherapy (IMRT) would lead to improved dosimetry for the breast and regional nodes. METHODS AND MATERIALS: Ten patients with left-sided breast cancer were selected. The clinical target volume included left breast and internal mammillary (IM), supraclavicular (SC), and axillary (AX) nodes. The critical structures included heart, right and left lungs, contralateral breast, esophagus, thyroid, and humeral head. Conventional and a series of IMRT plans were generated for comparison. RESULTS: The average heart D(3) was reduced from 31.4 +/- 18.9 with three-dimensional conformal radiotherapy (3D-CRT) to 15 +/- 7.2 Gy with 9-field (9-FLD IMRT). The average left lung D(30) was also decreased from 27.9 +/- 11.5 Gy (3D-CRT) to 12.6 +/- 8.2 Gy (9-FLD IMRT). The average contralateral breast D(2) was reduced from 4.4 +/- 5.3 Gy (3D-CRT) to 1.8 +/- 1.2 Gy (4-FLD IMRT). Esophagus D(2) was increased from 9.3 +/- 8.1 Gy (3D-CRT) to 29.4 +/- 5.4 (9-FLD IMRT); thyroid D(50) was increased from 0.9 +/- 0.6 Gy (3D-CRT) to 11.9 +/- 6.6 (9-FLD IMRT); humeral head D(2) was increased from 36.1 +/- 13.1 Gy (3D-CRT) to 39.9 +/- 6.5 (9-FLD IMRT). CONCLUSIONS: The use of IMRT improves breast and regional node coverage while decreasing doses to the lungs, heart, and contralateral breast when compared with 3D-CRT. Doses to esophagus, thyroid, and humeral head, however, were increased with IMRT.

Cuttino LW, Todor D, Pacyna L, Lin PS, Arthur DW. · Department of Radiation Oncology, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, VA 23298-0058, USA. · Am J Clin Oncol. · Pubmed #17023782 No free full text.

Abstract: OBJECTIVE: This study is an evaluation of the biologic equivalence of the dose prescriptions for brachytherapy and 3-dimensional conformal external beam radiotherapy (3D-CRT) accelerated partial breast irradiation (APBI), using actual patient dose matrix data, and is based on the concept of equivalent uniform biologically effective dose (EUBED). This formalism allows a nonuniform dose distribution to be reduced to an equivalent uniform dose, while also accounting for fraction size. MATERIALS AND METHODS: Five computed tomography scans were selected from a group of patients treated with multicatheter interstitial APBI. Dose matrices for the brachytherapy plans were computed and analyzed with in-house software. For each patient, the EUBED for the brachytherapy dose matrix was generated based on calculations performed at the voxel-level. These EUBED values were then used to calculate the biologically equivalent fraction size for 3D-CRT (eud). RESULTS: The mean equivalent fraction size (eudmean) and maximum equivalent fraction size (eudmax) were calculated for each patient using 100 different values of the alpha/beta ratio. The eudmean ranged from 3.67 to 3.69 Gy, while the eudmax ranged from 3.79 to 3.82 Gy. For all values of the alpha/beta ratio, the maximum fraction size calculated to deliver a biologically equivalent dose with 3D-CRT was 3.82 Gy, with an equivalent total prescription dose of 38.2 Gy. CONCLUSION: Utilizing a wide range of established radiobiological parameters, this study suggests that the maximum fraction size needed to deliver a biologically equivalent dose using 3D-CRT is 3.82 Gy, supporting the continued use of 3.85Gy BID in the current national cooperative trial.

Arthur DW, Cuttino LW, Neuschatz AC, Koo DT, Morris MM, Bear HD, Kaplan BJ, Dawson K, Wazer DE. · Deparment of Radiation Oncology, Virginia Commonwealth University, Medical College of Virginia Campus, 401 College Street, Box 58, Richmond, Virginia 23298, USA. · Ann Surg Oncol. · Pubmed #16614879 No free full text.

Abstract: BACKGROUND: We evaluated the necessity of a tumor bed boost after whole-breast radiotherapy for early-stage breast cancer after breast-conserving surgery and negative re-excision. METHODS: Of patients treated at the Virginia Commonwealth and Tufts Universities with breast-conservation therapy for early-stage breast cancer between 1983 and 1999, 205 required re-excision of the tumor cavity to obtain clear margins and were found to be without residual disease. Adjuvant conventionally fractionated whole-breast radiotherapy was given to a total dose of 50 Gy in 25 fractions. The tumor bed boost was omitted. RESULTS: The median follow-up was 98 months (range, 6-229 months). The tumor histological diagnosis was primarily infiltrating ductal carcinoma (183 cases; 89%). Nodal involvement was documented in 49 cases (24%). There were four documented recurrences at the tumor bed site. Five in-breast recurrences were documented to be in a location removed from the tumor bed. The overall Kaplan-Meier 15-year in-breast control rate was 92.4%, and the freedom from true recurrence rate was 97.6%. CONCLUSIONS: The findings support the concept that postlumpectomy radiotherapy can be tailored according to the degree of surgical resection. There is an easily identifiable subgroup of patients who can avoid a tumor bed boost, thus resulting in a reduced treatment time and improved cosmesis, while maintaining local control rates that approach 100%. The data suggest that in patients who undergo a negative re-excision, treatment with whole-breast radiotherapy to 50 Gy is a sufficient dose to maximally reduce the risk of local recurrence.

Wazer DE, Kaufman S, Cuttino L, DiPetrillo T, Arthur DW. · Department of Radiation Oncology, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA 02111, and Department of Radiation Oncology, Rhode Island Hospital, Providence, RI, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #16246495 No free full text.

Abstract: PURPOSE: To perform a detailed analysis of variables associated with late tissue effects of high-dose-rate (HDR) interstitial brachytherapy accelerated partial breast irradiation (APBI) in a large cohort of patients with prolonged follow-up. METHODS AND MATERIALS: Beginning in 1995, 75 women with Stage I/II breast cancer were enrolled in identical institutional trials evaluating APBI as monotherapy after lumpectomy. Patients eligible included those with T1-2, N0-1 (<or=3 nodes positive), M0 tumors of nonlobular histology with negative surgical margins, no extracapsular nodal extension, and negative results on postexcision mammogram. All patients underwent surgical excision and postoperative irradiation with HDR interstitial brachytherapy. The planning target volume was defined as the excision cavity plus a 2-cm margin. Treatment was delivered with a high-activity Ir-192 source at 3.4 Gy per fraction twice daily for 5 days to a total dose of 34 Gy. Dosimetric analyses were performed with three-dimensional postimplant dose and volume reconstructions. All patients were evaluated at 3-6-month intervals and assessed with a standardized cosmetic rating scale and according to Radiation Therapy Oncology Group late normal tissue toxicity scoring criteria. Clinical and therapy-related features were analyzed for their relationship to cosmetic outcome and toxicity rating. Clinical features analyzed included age, volume of resection, history of diabetes or hypertension, extent of axillary surgery, and systemic therapies. Therapy-related features analyzed included volume of tissue encompassed by the 100%, 150%, and 200% isodose lines (V100, V150, and V200, respectively), the dose homogeneity index (DHI), number of source dwell positions, and planar separation. RESULTS: The median follow-up of all patients was 73 months (range, 43-118 months). The cosmetic outcome at last follow-up was rated as excellent, good, and fair/poor in 67%, 24%, and 9% of patients, respectively. Suboptimal cosmetic outcome was significantly associated with the number of source dwell positions, V150, and V200 and inversely associated with DHI (0.77 vs. 0.73; p=0.05). Late skin toxicity was rated as Grade 0, 1, or 2 in 77%, 19%, and 4% of patients, respectively. The risk of Grade 1/2 skin toxicity was significantly associated with V150 and V200 and inversely associated with DHI (0.77 vs. 0.71; p=0.009). Late subcutaneous toxicity was rated as Grade 0, 1, 2, 3, or 4 in 55%, 15%, 12%, 5%, and 13% of patients, respectively. The risk of Grade 0/1 vs. Grade 2-4 subcutaneous toxicity was significantly associated only with a lower value of DHI (0.77 vs. 0.73; p=0.02). To further explore factors that might contribute to the risk of fat necrosis (symptomatic or asymptomatic), a separate analysis showed that only dose hotspots as reflected in V150 and V200 were significantly associated with elevated risk. The use of adriamycin-based chemotherapy after APBI was found to be associated with a significant increase in the incidence of higher-grade skin toxicity and a higher risk of fat necrosis and suboptimal cosmetic outcome. Patient age, volume of resection, extent of axillary surgery, a history of diabetes or hypertension, and the use of tamoxifen were not found to be significantly associated with cosmetic outcome or late normal tissue complications. CONCLUSIONS: Long-term cosmetic results and the risk of late skin and subcutaneous toxicity after APBI with interstitial HDR brachytherapy can be correlated with specific treatment-related variables. These data provide dosimetric parameters that might be used to minimize the risk of normal tissue injury after APBI interstitial brachytherapy.

Alpert TE, Kuerer HM, Arthur DW, Lannin DR, Haffty BG. · Department of Radiation Oncology, Upstate Medical University, Syracuse, NY, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #16199315 No free full text.

Abstract: PURPOSE: To compare outcomes of salvage mastectomy (SM) and salvage breast-conserving surgery (SBCS) and study the feasibility of SBCS. METHODS AND MATERIALS: Of 2,038 patients treated with breast-conserving therapy at Yale-New Haven Hospital before 1999, 166 sustained an ipsilateral breast tumor recurrence (IBTR). Outcomes and prognostic factors of patients treated with SM or SBCS were compared. Patients were considered amenable to SBCS if the recurrence was localized on mammogram and physical examination, and had pathologic size < 3 cm, confined to the biopsy site, without skin or lymphovascular invasion, and with < or = 3 positive nodes. RESULTS: Of the 146 patients definitively managed at IBTR, surgery was SM (n = 116) or SBCS (n = 30). The median length of follow-up after IBTR was 13.8 years. The SM and SBCS cohorts had no significant differences, except at IBTR the SM cohort had a greater tumor size (p = 0.049). Of the SM cohort, 65.5% were considered appropriate for SBCS, and a localized relapse was predicted by estrogen-receptor positive, diploid, and detection of recurrence by mammogram. Multicentric disease correlated with BRCA1/2 mutation, estrogen-receptor negative, lymph node positive at relapse, and detection of recurrence by physical examination. Survival after IBTR was 64.5% at 10 years, with no significant difference between SM (65.7%) and SBCS (58.0%). Only 2 patients in the SBCS cohort subsequently had a second IBTR, and were salvaged with mastectomy. CONCLUSIONS: While mastectomy is considered the standard surgical salvage of IBTR, SBCS is feasible and prognostic factors are related to favorable tumor biology and early detection. Patients with BRCA1/2 germline mutations may be less appropriate for SBCS, as multicentric disease was more prevalent. Patients who underwent SBCS had comparable outcomes as those who underwent SM, but remain at continued risk for IBTR. A prospective trial evaluating repeat lumpectomy and partial breast reirradiation is discussed.

Cuttino LW, Todor D, Arthur DW. · Department of Radiation Oncology, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, VA 23298-0058, USA. · Brachytherapy. · Pubmed #15737901 No free full text.

Abstract: PURPOSE: To evaluate the feasibility and dosimetric reliability of a CT-guided method of catheter insertion for accelerated partial breast brachytherapy (APBB). MATERIALS AND METHODS: From 1995 to 2002, 77 patients were treated with APBB using a multi-catheter low-dose-rate or high-dose-rate approach. Within that timeframe, 29 patients with early stage invasive breast cancer were treated with high-dose-rate partial breast brachytherapy and had CT scans of the brachytherapy implant available for analysis. Initially, catheter insertion was accomplished in the operating room at the time of lumpectomy using standard free-hand insertion techniques under fluoroscopic guidance and subsequent orthogonal film dosimetry. To improve the efficiency and quality of the technique, the procedure was moved to the departmental CT-simulation suite where the catheters were placed with CT guidance. Basic guidelines of needle insertion and implant construction were followed to assure appropriate intercatheter and interplanar spacing that allowed optimal dosimetric coverage of the target volume. Target volumes were delineated and a treatment plan generated using a 3D planning system (Varian Brachyvision). PTV 1 cm was defined as the lumpectomy cavity plus 1 cm and PTV 2 cm as the lumpectomy cavity plus 2 cm. Target coverage goals were set as delivery of 100% of the prescribed dose to >95% of PTV 1 cm and >90% of the dose to >90% of PTV 2 cm. Dose homogeneity index (DHI) was defined as (V150%-V100%/V100%) with a goal of achieving >0.75. Fifteen patients were treated using the initial method and 14 patients using the CT-guided technique. Targets were retrospectively entered in the initial group and dose volume histogram analysis completed on all patients. The ability of each technique to achieve the target coverage and homogeneity goals was compared. RESULTS: With the change from traditional techniques to a CT-guided technique, the percentage of patients satisfying all dosimetric goals increased from 42% to 93%. Mean dose coverage (defined as the percentage of PTV 2 cm receiving 90% of the prescribed dose) increased from 89% to 95% (p=0.007) and the mean DHI increased from 0.77 to 0.82 with the new technique (p < 0.005). CONCLUSIONS: Reproducible target coverage and dose homogeneity were achieved with CT-guided catheter insertion and 3D planning software. Catheters can be optimally placed with intraoperative CT evaluation and 3D planning software allows improved implant visualization resulting in optimized dosimetry. Improvements in target coverage and DHI may translate into optimized local control and improved cosmesis with a corresponding reduction in the risk of complications.

Vicini FA, Arthur DW, Wazer DE. · No affiliation provided · Brachytherapy. · Pubmed #15062163 No free full text.

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