Breast Neoplasms: Rabinovitch R

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.

White JR, Halberg FE, Rabinovitch R, Green S, Haffty BG, Solin LJ, Strom EA, Taylor ME, Edge SB. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226-4801 , USA. · J Am Coll Radiol. · Pubmed #18514949 No free full text.

Abstract: 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.

Rabinovitch R, Kavanagh B. · No affiliation provided · J Clin Oncol. · Pubmed #19349536 No free full text.

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Rabinovitch R. · No affiliation provided · Clin Breast Cancer. · Pubmed #15899067 No free full text.

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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.

Ibbott GS, Hanson WF, O'Meara E, Kuske RR, Arthur D, Rabinovitch R, White J, Wilenzick RM, Harris I, Tailor RC. · Radiological Physics Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18035213 links to  free full text

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

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.

Vicini F, Winter K, Straube W, Wong J, Pass H, Rabinovitch R, Chafe S, Arthur D, Petersen I, McCormick B. · Department of Radiation Oncology, Beaumont Cancer Institute, William Beaumont Hospital, Royal Oak, MI 48073, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #16198508 No free full text.

Abstract: BACKGROUND: This prospective study (Radiation Therapy Oncology Group Study 0319) examines the use of three-dimensional conformal external beam radiation therapy to deliver accelerated partial breast irradiation. Reproducibility, as measured by technical feasibility, was the primary end point with the goal of demonstrating whether the technique is widely applicable in a multicenter setting before a Phase III trial is undertaken. METHODS AND MATERIALS: This study was designed such that if fewer than 5 cases out of the first 42 patients evaluable were scored as unacceptable, the treatment would be considered reproducible. Patients received 38.5 Gy in 3.85 Gy/fraction delivered twice daily. The clinical target volume included the lumpectomy cavity plus a 10-15-mm margin bounded by 5 mm within the skin surface and the lung-chest wall interface. The planning target volume (PTV) included the clinical target volume plus a 10-mm margin. Treatment plans were judged as follows: (1) No variations (total coverage), 95% isodose surface covers 100% of the PTV and all specified critical normal tissue dose-volume histogram (DVH) limits met. (2) Minor variation (marginal coverage), 95% isodose surface covers between > or = 95% and <100% of the PTV. No portion of PTV receives <93% of prescription (isocenter) dose. All specified critical normal tissue DVH limits fall within 5% of the guidelines. (3) Major variation (miss), 95% isodose surface covers <95% of the PTV. Portion of PTV receives <93% of prescription isocenter dose. Any critical normal tissue DVH limit exceeds 5% of the specified value. RESULTS: A total of 58 patients were enrolled on this study between 8/15/03 and 4/30/04, 5 of whom were ineligible or did not receive protocol treatment. Two additional patients were excluded, one because the on-study form was not submitted, and the other because no treatment planning material was submitted. This primary end point analysis is based on the first 42 (out of 51) evaluable patients, which were accrued from 17 different institutions (31 centers were credentialed for case enrollment, but because of rapid accrual, not all centers were able to submit cases before trial closure). These 42 patients had the following characteristics: median age was 61 years; 48% had a maximum tumor dimension of <1 cm; 86% had invasive ductal carcinoma; 64% were postmenopausal; the location of tumor was upper outer for 40% and upper central for 21%; 79% had no chemotherapy, and 64% had no hormonal therapy. There were 4 cases with major variations (all 4 related to normal tissue DVHs exceeding 5% of the specified limit). A total of 32 cases with minor variations in treatment plans were detected (16 related to normal tissue DVHs exceeding the specified limits [by < or = 5%], 6 related to suboptimal coverage of the PTV, and 10 related to both). There were 6 cases with no variations. Of the 51 total evaluable patients, 1 additional major variation was noted (PTV receiving <93% of the prescription dose). An additional 5 cases with minor variations in treatment plans were detected (3 related to normal tissue DVHs exceeding the specified limits [by < or = 5%], 1 related to suboptimal coverage of the PTV, and 1 related to both). There were 3 more cases with no variations. CONCLUSION: Accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy was shown in this preliminary analysis of the first 42 evaluable patients to be technically feasible and reproducible in a multi-institutional trial using exceptionally strict dosimetric criteria.

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.

Brooks G, Borges V, Singh M, Rabinovitch R, Finlayson C, Elias A. · Department of Medicine, University of Colorado School of Medicine Aurora, Colorado 80045, USA. · Oncology (Williston Park). · Pubmed #18980024 No free full text.

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McCammon R, Finlayson C, Schwer A, Rabinovitch R. · Department of Radiation Oncology, University of Colorado Comprehensive Cancer Center, Aurora, Colorado 80045-0508, USA. · Cancer. · Pubmed #18543316 No free full text.

Abstract: BACKGROUND: Randomized trials provide evidence for improved outcomes with postmastectomy radiotherapy (PMRT) in high-risk patients. It has been suggested that patients with T3N0 breast cancer represent a favorable subgroup for which PMRT renders little benefit. In the current study, the authors used a United States population database to evaluate PMRT in this subgroup. METHODS: The cause-specific survival (CSS) and overall survival (OS) of women with T3N0M0 breast cancer in the Surveillance, Epidemiology, and End Results database after mastectomy and axillary staging from 1988 to 2002 were analyzed. Univariate analysis was performed to relate CSS with PMRT (yes vs no), tumor size (< or =7 cm vs >7 cm), grade (1 vs 2 or 3), patient age (< or =50 years vs >50 years), the number of lymph nodes dissected (< or =13 vs >13), and the era treated (1988-1997 vs 1998-2002). Multivariate analyses for CSS and OS were also performed. RESULTS: In total, 1865 women met the analysis criteria for OS; CSS data were available for 98.8% of those women. Of the women who were diagnosed during the era from 1988 to 1997, 22% received PMRT, and that rate increased to 41% during the era from 1998 to 2002. The actuarial 10-year CSS for those who received PMRT versus those who did not receive PMRT was 81.6% versus 79.8%, respectively (P = .38). PMRT was not associated with a CSS benefit in any subgroup, a finding that persisted in multivariate analyses. Women who received PMRT had an increased 10-year OS rate (70.7% vs 58.4%; P < .001) that was confined to women aged >50 years in a subgroup analysis. CONCLUSIONS: This retrospective, population-based analysis demonstrated no increase in CSS with PMRT for women with T3N0 breast cancer, lending further support to the hypothesis that T3N0 disease postmastectomy represents a favorable subset of locally advanced breast cancer. The increased OS associated with PMRT in the absence of improved CSS likely reflects patient selection in this nonrandomized dataset. Prospective evaluation of PMRT in this population subset is warranted.

Rabinovitch R, Ballonoff A, Newman F, Finlayson C. · Department of Radiation Oncology, University of Colorado Cancer Center, Aurora, CO 80045, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #17967511 No free full text.

Abstract: BACKGROUND: Biopsy of the breast sentinel lymph node (SLN) is now a standard staging procedure for early-stage invasive breast cancer. The anatomic location of the breast SLN and its relationship to standard radiation fields has not been described. METHODS AND MATERIALS: A retrospective review of radiotherapy treatment planning data sets was performed in patients with breast cancer who had undergone SLN biopsy, and those with a surgical clip at the SLN biopsy site were identified. The location of the clip was evaluated relative to vertebral body level on an anterior-posterior digitally reconstructed radiograph, treated whole-breast tangential radiation fields, and standard axillary fields in 106 data sets meeting these criteria. RESULTS: The breast SLN varied in vertebral body level position, ranging from T2 to T7 but most commonly opposite T4. The SLN clip was located below the base of the clavicle in 90%, and hence would be excluded from standard axillary radiotherapy fields where the inferior border is placed at this level. The clip was within the irradiated whole-breast tangent fields in 78%, beneath the superior-posterior corner multileaf collimators in 12%, and outside the tangent field borders in 10%. CONCLUSIONS: Standard axillary fields do not encompass the lymph nodes at highest risk of containing tumor in breast cancer patients. Elimination of the superior-posterior corner MLCs from the tangent field design would result in inclusion of the breast SLN in 90% of patients treated with standard whole-breast irradiation.

Bowles DW, Rabinovitch R, Borges V, Urquhart A, Singh M, Finlayson C, Elias A. · Department of Medicine, University of Colorado, Aurora, USA. · Oncology (Williston Park). · Pubmed #17926799 No free full text.

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Menter A, Urquhart A, Borges V, Rabinovitch R, Singh M, Robinson W, Seligman P, Finlayson C, Elias A. · Division of Medical Oncology, University of Colorado, Health Sciences Center, USA. · Oncology (Williston Park). · Pubmed #16986350 No free full text.

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Urquhart A, Borges V, Rabinovitch R, Singh M, Robinson W, Seligman P, Arya J, Finlayson C, Elias A. · Division of Medical Oncology, Denver Health Medical Center, USA. · Oncology (Williston Park). · Pubmed #15828548 No free full text.

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Harms SE, Rabinovitch R, Julian TB, Rafferty E, Masood S, Weatherall P. · University of Arkansas for Medical Sciences, Little Rock 72205, USA. · Breast J. · Pubmed #15330873 No free full text.

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McCormick B, Strom E, Craighead PS, Kuske R, Hudis C, Ley J, Margolis L, Meyerwitz B, Morris E, Petrek J, Pierce L, Pisansky T, Rabinovitch R, Sneige N, Vicini F, Unger D, Winter K, Anonymous00353. · No affiliation provided · Int J Radiat Oncol Biol Phys. · Pubmed #11641016 No free full text.

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Rabinovitch R, Finlayson C, Pan Z, Lewin J, Humphries S, Biffl W, Franciose R. · Department of Radiation Oncology, University of Colorado Cancer Center, Denver, CO 80224, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #10802354 No free full text.

Abstract: PURPOSE: Breast radiotherapy (BrRT) often includes a "boost" to the lumpectomy bed. Selection of an appropriate electron energy and field size is based upon the dimensions and location of the surgical cavity. This study was performed to confirm our impression that ultrasound (US) inadequately defines the volume at risk compared to radiographic evaluation of surgical clips placed within the operative bed at the time of lumpectomy. METHODS AND MATERIALS Twenty-nine women treated with BrRT at our institution between 1996-1998 were prospectively identified as having surgical clips within the lumpectomy cavity. These patients underwent both US evaluation and radiographic evaluation of the clips to independently define two sets of transverse (T), longitudinal (L), and depth (D) measurements for each cavity. Volumes (V) were calculated for each method, assuming the cavity to be a box (V = T x L x D). Twenty-one women began BrRT following a median postoperative interval of 6 weeks (Group A), and 8 after 24 weeks (Group B) due to delivery of systemic therapy. RESULTS: Dimensions derived by US were smaller than the clip method in 22/29 of T, 25/29 of L, and 23/29 of D, or 80% of all linear measurements. A paired t-test demonstrated the difference between the methods to be statistically significant: T: p = 0.0004; L: p = 0.0001; D: p = 0.0004; and V: p = 0.0001. This underestimation by US did not fit any predictable pattern. Although the mean difference between methods (clips - US) was only 1.3, 1.9, and 1.1 cm for T, L, and D, respectively, differences ranged up to 5. 7, 9.2, and 5.5 cm for T, L, and D. The bias toward underestimation of V by US was significantly greater for Group B than Group A (p = 0. 03). CONCLUSIONS: US significantly underestimates all three dimensions of the lumpectomy cavity and hence the volume at risk compared to radiographic evaluation of surgical clips. Breast-conserving surgery should include placement of clips at the margins of the lumpectomy cavity (superior, inferior, medial, lateral, and posterior) to aid in radiotherapy treatment planning. US should not be utilized to guide the design of the boost field as it will result in inappropriate selection of lower electron energies and smaller field sizes (geographical miss), particularly among patients who receive chemotherapy prior to breast radiotherapy.

Heimbach JK, Biffl WL, Mitchell EL, Finlayson CA, Schwartzberg BS, Myers A, Rabinovitch R, Franciose RJ. · Department of Surgery, Denver Health Medical Center and University of Colorado Health Sciences Center, 80204, USA. · Am J Surg. · Pubmed #10670854 No free full text.

Abstract: BACKGROUND: Breast conservation therapy (BCT) offers equivalent survival to modified radical mastectomy in patients with early-stage (I and IIa) breast cancer, but is utilized in less than 50% of eligible patients. While patient demographics have been linked to BCT rates, we suspected that physician influence was a major factor. The purpose of this study was to compare BCT at three affiliated centers staffed by similarly trained surgeons yet serving widely disparate populations, in order to assess the importance of physician influence on the utilization of BCT. METHODS: Tumor registry data were reviewed from 1993 through 1997 at affiliated city/county (CH), university (UH), and private hospitals (PH). Data were analyzed for clinical stage, treatment, and age of patient. RESULTS: The utilization of BCT for stage I and IIa breast cancer is similar at the three hospitals: 45% of patients at CH, 55% of patient at UH, and 57% of patients at PH (P>0.05). Rates of BCT were similar across all patient age groups at all sites. CONCLUSIONS: Similar BCT utilization rates can be achieved despite widely disparate patient populations. The three affiliated hospitals are staffed by surgeons with similar training, and all offer a multidisciplinary approach to breast cancer care. This suggests that physician influence may override patients' socioeconomic issues in providing optimal breast cancer therapy.