Biomedical subjects
Abram Recht
Publications and source records attributed to Abram Recht.
Accelerated partial-breast irradiation using proton beams: initial clinical experience.
PURPOSE: We present our initial clinical experience with proton, three-dimensional, conformal, external beam, partial-breast irradiation (3D-CPBI). METHODS AND MATERIALS: Twenty patients with Stage I breast cancer were treated with proton 3D-CPBI in a Phase I/II clinical trial. Patients were followed at 3 to 4 weeks, 6 to 8 weeks, 6 months, and every 6 months thereafter for recurrent disease, cosmetic outcome, toxicity, and patient satisfaction. RESULTS: With a median follow-up of 12 months (range, 8-22 months), no recurrent disease has been detected. Global breast cosmesis was judged by physicians to be good or excellent in 89% and 100% of cases at 6 months and 12 months, respectively. Patients rated global breast cosmesis as good or excellent in 100% of cases at both 6 and 12 months. Proton 3D-CPBI produced significant acute skin toxicity with moderate to severe skin color changes in 79% of patients at 3 to 4 weeks and moderate to severe moist desquamation in 22% of patients at 6 to 8 weeks. Telangiectasia was noted in 3 patients. Three patients reported rib tenderness in the treated area, and one rib fracture was documented. At last follow-up, 95% of patients reported total satisfaction with proton 3D-CPBI. CONCLUSIONS: Based on our study results, proton 3D-CPBI offers good-to-excellent cosmetic outcomes in 89% to 100% of patients at 6-month and 12-month follow-up and nearly universal patient satisfaction. However, proton 3D-CPBI, as used in this study, does result in significant acute skin toxicity and may potentially be associated with late skin (telangiectasia) and rib toxicity. Because of the dosimetric advantages of proton 3D-CPBI, technique modifications are being explored to improve acute skin tolerance.
Which breast cancer patients should really worry about radiation-induced heart disease--and how much?
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Factors affecting outcome for young women with early stage invasive breast cancer treated with breast-conserving therapy.
BACKGROUND: Young women have worse outcome following breast-conserving therapy (BCT) than do older patients in many studies. We examined how clinical, pathological, and treatment factors affect these results. METHODS: Between 1993 and 1999, 130 patients age 40 years or younger with stage I or II breast cancer were treated with BCT. The median radiation dose to the tumor bed was 61 Gy; 80% of patients received chemotherapy; and 29% of 72 patients with estrogen-receptor positive tumors received tamoxifen. Median follow-up was 93 months. RESULTS: Fifteen patients (12%) developed an ipsilateral breast tumor recurrence (IBTR), with or without other simultaneous failure sites. The Kaplan-Meier 5- and 8-year actuarial rates were 8% and 14%, respectively. The 74 patients with grade 3 tumors had a higher IBTR rate (8-year actuarial rate, 18%) than the 54 patients with grade 1-2 lesions (7%) (P = 0.09). Six patients developed contralateral breast cancers, and 17 developed distant metastases (DM). The 8-year actuarial rates for freedom-from-DM, relapse-free survival, and overall survival were 85%, 72% and 96%, respectively. CONCLUSION: This represents one of the largest series of young women treated with BCT, using an approach similar to current practice. The IBTR rate was substantially lower than in many past studies, but still higher than would be expected for older women. This appeared largely due to the increased rate of IBTR in patients with grade 3 tumors. If this observation is confirmed, further analysis of this subgroup may lead to ways of reducing the risk of IBTR.
A prospective study of conservative surgery without radiation therapy in select patients with Stage I breast cancer.
PURPOSE: The effectiveness of radiation therapy (RT) in reducing local recurrence after breast-conserving surgery (BCS) in unselected patients with early stage invasive breast cancer has been demonstrated in multiple randomized trials. Whether a subset of women can achieve local control without RT is unknown. In 1986, we initiated a prospective one-arm trial of BCS alone for highly selected breast-cancer patients. This report updates those results. METHODS AND MATERIALS: Eighty-seven (of 90 planned) patients enrolled from 1986 until closure in 1992, when a predefined stopping boundary was crossed. Patients were required to have a unicentric, T1, pathologic node-negative invasive ductal, mucinous, or tubular carcinoma without an extensive intraductal component or lymphatic-vessel invasion. Surgery included local excision with margins of at least 1 cm or a negative re-excision. No RT or systemic therapy was given. RESULTS: Results are available on 81 patients (median follow-up, 86 months). Nineteen patients (23%) had local recurrence (LR) as a first site of failure (average annual LR: 3.5 per 100 patient-years of follow-up). Other sites of first failure included 1 ipsilateral axilla, 2 contralateral breast cancers, and 4 distant metastases. Six patients developed other (nonbreast) malignancies. Nine patients have died, 4 of metastatic breast cancer and 5 of unrelated causes. CONCLUSIONS: Even in this highly selected cohort, a substantial risk of local recurrence occurred after BCS alone with margins of 1.0 cm or more. These results suggest that with the possible exception of elderly women with comorbid conditions, radiation therapy after BCS remains standard treatment.
Initial dosimetric experience using simple three-dimensional conformal external-beam accelerated partial-breast irradiation.
PURPOSE: Several accelerated partial-breast irradiation (APBI) techniques are being investigated in patients with early-stage breast cancer. We present our initial experience using three-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS: Sixty-one patients with tumors of 2 cm or less and negative axillary nodes were treated with 3D-CRT accelerated partial-breast irradiation (APBI) between August 2003 and March 2005. The prescribed radiation dose was 32 Gy in 4-Gy fractions given twice daily. Efforts were made to minimize the number of beams required to achieve adequate planning target volume (PTV) coverage. RESULTS: A combination of photons and electrons was used in 85% of patients. A three-field technique that consisted of opposed, conformal tangential photons and enface electrons was employed in 43 patients (70%). Nine patients (15%) were treated with a four-field arrangement, which consisted of three photon fields and enface electrons. Mean PTV volumes that received 100%, 95%, and 90% of the prescribed dose were 93% +/- 7%, 97% +/- 4%, and 98% +/- 2%, respectively. Dose inhomogeneity exceeded 10% in only 7 patients (11%). Mean doses to the ipsilateral lung and heart were 1.8 Gy and 0.8 Gy, respectively. CONCLUSIONS: Simple 3D-CRT techniques of APBI can achieve appropriate PTV coverage while offering significant normal-tissue sparing. Therefore, this noninvasive approach may increase the availability of APBI to patients with early-stage breast cancer.
Update on accelerated partial-breast irradiation.
Progress in radiotherapy technology, particularly the advent of CT-guided simulation and three-dimensional conformal planning, has given the radiation oncologist the ability to precisely treat part of the breast, instead of the whole breast, using either brachytherapy or external-beam techniques. Treating such a limited area may allow the course of treatment for patients with early-stage breast cancer to be drastically shortened and could reduce toxicity to other organs. This article summarizes the rationale for accelerated partial-breast irradiation (APBI), techniques for performing it, and outcome to date of studies of APBI.
New trends in breast cancer management: is the era of immediate breast reconstruction changing?
OBJECTIVE: Review of available literature on the topic of breast reconstruction and radiation is presented. Factors influencing the decision-making process in breast reconstruction are analyzed. New trends of immediate breast reconstruction are presented. SUMMARY BACKGROUND DATA: New indications for postmastectomy radiation have caused a dramatic increase in the number of radiated patients presenting for breast reconstruction. The major studies and their impact on breast cancer management practice are analyzed. Unsatisfactory results of conventional immediate reconstruction techniques followed by radiotherapy led to a new treatment algorithm for these patients. If the need for postoperative radiation therapy is known, a delayed reconstruction should be considered. When an immediate reconstruction is still desired despite the certainty of postoperative radiotherapy, reconstructive options should be based on tissue characteristics and blood supply. Autologous tissue reconstruction options should be given a priority in an order reflecting superiority of vascularity and resistance to radiation: latissimus dorsi flap, free TRAM or pedicled TRAM without any contralateral components of tissue, pedicled TRAM/midabdominal TRAM, and perforator flap. CONCLUSIONS: When the indications for postoperative radiotherapy are unknown, premastectomy sentinel node biopsy, delayed-immediate reconstruction, or delayed reconstruction is preferable.
NCCN Task Force Report: Adjuvant Therapy for Breast Cancer.
The National Comprehensive Cancer Network (NCCN) first published the NCCN Breast Cancer Treatment Guidelines in 1996. The Guidelines address the treatment of all stages of breast cancer across the spectrum of patient care and have been updated yearly. Adjuvant therapy for breast cancer has undergone an especially rapid evolution over the past few years. Therefore, the NCCN Breast Cancer Guidelines Panel was supplemented by additional experts to form the Adjuvant Therapy Task Force to provide a forum for an extended discussion and expanded input to the adjuvant therapy recommendations for the Breast Cancer Treatment Guidelines. Issues discussed included methods of risk-stratification for recurrence; how biologic markers such as HER2 status, quantitative estrogen receptor, or genetic markers can be incorporated as prognostic or predictive factors; and how age, menopausal status, and estrogen receptor levels impact benefits from chemotherapy and endocrine therapy. Additionally, the task force discussed the strategies for use of aromatase inhibitors in postmenopausal women and the potential incorporation of trastuzumab into adjuvant therapy of women with HER2/neu positive breast cancer. This supplement summarizes the background data and ensuing discussion from the Adjuvant Task Force meeting.
Sequencing of chemotherapy and radiation therapy in early-stage breast cancer: updated results of a prospective randomized trial.
PURPOSE: The optimal integration of chemotherapy with radiation (RT) for patients with early-stage breast cancer remains uncertain. We present the long-term results of a prospective randomized trial to address this question. PATIENTS AND METHODS: Two hundred forty-four patients were randomly assigned after conservative breast surgery to receive 12 weeks of cyclophosphamide, doxorubicin, methotrexate, fluorouracil, and prednisone (CAMFP) before RT (CT-first) or after RT (RT-first). Median follow-up for surviving patients was 135 months. RESULTS: There were no significant differences between the CT-first and RT-first arms in time to any event, distant metastasis, or death. Sites of first failure were also not significantly different. CONCLUSION: Among breast cancer patients treated with conservative surgery, there is no advantage to giving RT before adjuvant chemotherapy. However, this study does not have enough statistical power to rule out a clinically important survival benefit for either sequence.
Prognosis after local recurrence after conservative surgery and radiation for early-stage breast cancer.
PURPOSE: To determine the long-term prognosis of patients who develop a local recurrence (LR) after conservative surgery (CS) and radiation therapy (RT) for early-stage invasive breast cancer. METHODS AND MATERIALS: Between 1970 and 1987, 2102 patients with clinical Stage I-II breast cancer were treated with CS+RT. LR was defined as any recurrence within the ipsilateral breast with or without simultaneous regional nodal or distant metastasis. Patients were at risk for a LR until the first of distant metastases, second nonbreast malignancy, or death (DF/S/D). The final study population comprised 341 patients with LR. The median time to LR was 72 months. The median follow-up time after LR was 85 months. A proportional hazards model of time from LR to DF/S/D was done to investigate the influence of factors at initial diagnosis and at LR on subsequent outcome. RESULTS: The actuarial freedom from DF/S/D 5 years after LR was 65% and the survival was 81%. Variables significantly associated with time to DF/S/D were: LR histology (invasive vs. ductal carcinoma in situ, hazard ratio [HR] = 4.1, p < 0.0001); local therapy for LR (none vs. mastectomy or unknown, HR = 3.2, p < 0.0001; and CS +/- RT vs. mastectomy or unknown, HR = 2.0, p = 0.02); time to LR (< or =2 years vs. >5 years, HR = 2.6, p < 0.0001; and 2-5 years vs. >5 years, HR = 1.8, p = 0.006); and age at initial diagnosis (> or =60 vs. <60, HR = 1.6, p = 0.01). CONCLUSIONS: Many patients with LR after CS+RT have prolonged distant disease-free survival, particularly those able to be treated with mastectomy. Patients with a noninvasive LR, longer interval to LR, or age <60 had a longer time to distant failure, second malignancy, or death than other patients.
Should patients with lobular carcinoma in situ be irradiated? --not yet, but....
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Image-detected breast cancer: state of the art diagnosis and treatment.
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Lessons of studies of breast-conserving therapy with and without whole-breast irradiation for patient selection for partial-breast irradiation.
Partial-breast irradiation is a promising approach for treating patients with early-stage invasive breast cancer. There are still few studies of partial-breast irradiation that address critical issues, such as criteria for patient selection. However, an enormous body of experience has been accumulated regarding the results in patients treated with "conventional" breast-conserving therapy using whole-breast irradiation and for patients treated with conservative surgery without radiotherapy of any kind. This article will therefore review portions of this existing experience that may aid the development of partial-breast irradiation and give perspective on the overall role that partial-breast irradiation may ultimately play in our therapeutic armamentarium.
Is adjuvant hypofractionated radiotherapy appropriate for elderly patients with breast cancer?
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Young age and outcome for women with early-stage invasive breast carcinoma.
BACKGROUND: Patients with invasive breast carcinoma who are ages 35-40 years or younger at the time of diagnosis have been found in several studies to have worse prognosis and higher local failure rates after breast-conserving therapy (BCT) compared with older patients. However, it is uncertain whether specific clinical, pathologic, or treatment factors affect these results, or whether mastectomy yields a better outcome. METHODS: Articles addressing how patient age at the time of diagnosis affects treatment outcome were identified through the MEDLINE and CancerLit databases and the reference lists of relevant articles. RESULTS: Young age was found to remain an independent risk factor for worse outcome after either BCT or mastectomy. Limited evidence did not demonstrate a superior outcome with mastectomy compared with BCT. Recent studies of BCT still reported young age to be associated with higher local recurrence rates compared with that for older patients, but their interpretation was hampered by inadequate margin assessment for ductal carcinoma in situ. Adjuvant chemotherapy has been found to improve local control rates substantially for young patients after BCT. CONCLUSIONS: To the authors' knowledge, there are insufficient data to determine whether young patients have superior long-term outcome if treated by mastectomy compared with BCT, or whether having truly uninvolved margins abrogates their increased risk of local failure after BCT. When meticulous attention is given to surgical techniques and margin status, it appears that young age at the time of diagnosis need not be a contraindication to BCT.
Outcome after breast-conserving therapy for patients with stage I or II mucinous, medullary, or tubular breast carcinoma.
PURPOSE: To evaluate the site of first failure of patients with early-stage tubular, mucinous, and medullary breast carcinoma after breast-conserving therapy and compare their results with those of patients with infiltrating ductal carcinoma (IDC). METHODS AND MATERIALS: Twenty clinical Stage I and II patients with mucinous carcinoma, 27 with medullary carcinoma, 28 with tubular carcinoma, and 1055 with IDC were identified. The minimal potential follow-up was 10 years. RESULTS: No statistically significant difference (p = 0.15) was seen in the site of first failure between the four histologic types within the first 10 years after treatment. When the IDC tumors were omitted from the comparison, the failure patterns of the remaining three histologic types were not significantly different (p = 0.31). In a polychotomous logistic model, histologic type was not significantly associated with the site of first failure (all p >0.17). Local failure was significantly associated with age <50 years (p = 0.04), positive surgical margins (p = 0.007), lymphovascular invasion (p = 0.04), and tumors with an extensive intraductal component (p <0.001). Regional/distant/opposite breast failure was significantly associated with clinical Stage T2 tumors (p <0.001), four or more positive lymph nodes (p = 0.004), and lymphovascular invasion-positive tumors (p <0.001). Second malignancy or death was significantly associated with age at diagnosis >60 years (p <0.001) and lymphovascular invasion-positive tumors (p = 0.03). CONCLUSION: No statistically significant difference was noted in the site of first failure between patients with medullary, mucinous, or tubular carcinoma and patients with IDC. Although not statistically significant, we did note a trend toward a lower long-term rate of disease-free survival in patients with IDC.
A prospective study of concurrent cyclophosphamide/methotrexate/5-fluorouracil and reduced-dose radiotherapy in patients with early-stage breast carcinoma.
BACKGROUND: Concurrent administration of chemotherapy and radiotherapy has the potential advantage of delaying neither treatment and providing radiation sensitization. However, the optimal approach to concurrent treatment in women with early-stage breast carcinoma remains undefined. We present updated results of a prospective protocol of concurrent cyclophosphamide/methotrexate/5-fluorouracil (CMF) and reduced-dose radiotherapy, focusing on tumor control and patient tolerance. METHODS: One hundred twelve women with AJCC Stage I or Stage II breast carcinoma with 0-3 positive axillary lymph nodes were enrolled in a prospective single-arm study of concurrent CMF and reduced-dose radiotherapy (39.6 gray [Gy] to the whole breast, 16-Gy boost). A high proportion of women had risk factors associated with an increased risk of local disease recurrence, including age <40 (32%), close or positive margins (37%), or lymphatic/vascular invasion (51%). The median follow-up period was 94 months. RESULTS: The 5-year overall survival rate was 94%. By 60 months, 5 patients (4%) experienced local disease recurrence and 19 patients (17%) experienced distant metastasis. There were no isolated regional lymph node recurrences. Local disease recurrence occurred in 1 of 25 patients (4%), 1 of 16 patients (6%), and 3 of 70 patients (4%) with positive, close (<1 mm), and negative margins, respectively. One patient developed acute myelogenous leukemia. An additional patient developed Grade 2 pneumonitis. Cosmetic results were not recorded uniformly for all patients and therefore could not be reliably analyzed. CONCLUSIONS: Concurrent CMF and reduced-dose radiotherapy resulted in a low level of late toxicity and excellent local tumor control, despite the large proportion of patients with substantial risk factors for local disease recurrence. Future studies of concurrent regimens, particularly in patients at high risk of local disease recurrence, are warranted.