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Accelerated Breast Brachytherapy: an Effective and Convenient Alternative for Selected Patients With Early-Stage Breast Cancer

Posted on: Sunday, 8 May 2005, 03:00 CDT

INTRODUCTION

Breast cancer is the most common malignancy in the American female. It is estimated that more than 200,000 women will be diagnosed in the year 2004. With appropriate screening, most patients are detected at an early stage. And the local treatment options for these patients are either total mastectomy with or without reconstruction or breast conservation therapy (BCT). BCT consists of lumpectomy and axillary lymph node sampling followed by radiation therapy. There are six prospective phase 3 randomized studies in America and Europe with long follow-up (up to 20 years) showing equivalent local control and survival for the two treatment modalities.

In appropriately selected patients with early-stage breast cancer, a number of randomized trials have found that BCT results in survival equivalent to that documented with mastectomy.1-3 Despite these results, up to 50% of patients with early-stage breast cancer do not receive BCT. Additionally, it is estimated that 25% of women who receive a lumpectomy do not receive radiation therapy at all.4 Further randomized trials have been conducted to determine if radiation therapy can be omitted after lumpectomy, but to date no subset of patients has been identified that should be treated with surgery alone.

The current standard of care for BCT includes post-lumpectomy whole breast radiation therapy. However, there are several contemporary publications indicating that the primary benefit of radiation therapy is a reduction in the risk of local tumor recurrence, with little effect on the incidence of recurrence away from the tumor bed.5,6 During the past decade, this information has led researchers from single institutions and the Radiation Therapy Oncology Group to conduct prospective trials investigating 4- or 5- day breast brachytherapy as the radiation treatment regimen used in conjunction with lumpectomy. Brachytherapy, or internal radiation therapy, enables physicians to deliver a therapeutic dose of radiation to the tissue at highest risk for recurrence while minimizing exposure to the surrounding healthy tissue. Numerous clinical studies of both low-dose rate and high-dose rate brachytherapy for treatment of breast cancer have been conducted worldwide and demonstrate low local recurrence rates.7-18

These recently reported results have generated increased interest in the practice of brachytherapy for treatment of breast cancer. Such treatment may enable physicians to offer the benefits of BCT to more patients.

RATIONALES FOR ACCELERATED PARTIAL BREAST IRRADIATION

The conventional radiation therapy for early stage breast cancer uses external beam radiation from a linear accelerator to treat the whole breast for about 5-51/2 weeks, and then boost to the surgical bed with additional 1-2 weeks of daily treatment. This 6-7 week course of treatment is well tolerated and has a long track of record with multiple prospective phase-3 randomized trials showing similar efficacy with mastectomy in term of survival and local-regional control. The cosmesis after external beam irradiation is good to excellent in most patients. However, the logistical barrier of distance and time commitment could be difficult for many patients. The long course of daily treatment may not be convenient to some patients who live far from the radiation therapy clinic, have difficulty with transportation, or have busy lifestyles. Some patients may select mastectomy due to these inconvenient factors. In some extreme cases, patients choose lumpectomy alone at risk of higher breast failure, and this has been documented from the data collected by the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) registry.1 Despite attempts to eliminate radiation therapy in early stage patients after lumpectomy, this subgroup of patients has not yet be identified.2,3

Whole-breast irradiation with external beam (WBI) has the advantage of being easy to deliver and reproduce, and is much less operator dependent. WBI requires minimal time and effort from the physician. Whole-breast irradiation permanently affects a small volume of the lung, chest wall, and heart (for the left-sided breast), which can lead to a small but possible risk of late injury to the chest wall, radiation pneumonitis, and heart disease.

Late toxic effects of radiation therapy, although uncommon, can include radiation pneumonitis, cardiac events, arm edema, brachial plexopathy, and the risk of second malignancies. Such toxic effects can be minimized with current radiation delivery techniques and with careful delineation of the target volume.

In a retrospective analysis of 1624 women treated with conservative surgery and adjuvant breast irradiation at a single institution, the overall incidence of symptomatic radiation pneumonitis was 1.0% at a median follow-up of 77 months. The incidence of pneumonitis increased to 3% with the use of a supraclavicular radiation field, and to 8.8% when concurrent chemotherapy was administered. The incidence was only 1.3% in patients who received sequential chemotherapy.4

Controversy exists as to whether adjuvant radiation to the left chest wall or breast, with or without inclusion of the regional lymphatics, has a potential association with increased cardiac morbidity. A meta-analysis of 36 randomized studies of surgery alone (mastectomy or lumpectomy) versus surgery with radiation therapy performed between 1945 and 1985 has been done.5 No clear differences in overall survival were seen between the arms at 10 years. Radiation therapy was associated with a reduced risk of death due to breast cancer (odds ratio, 0.94, 95% CI, 0.88-1.00, P = 0.03). However, an increase in non-breast cancer deaths was seen in patients who received radiation therapy (odds ratio 1.24, 95% CI, 1.09-1.42, P = 0.002). The absolute increase in risk was particularly greater in women older than 60 years of age (15.3% versus 11.1%) than in women younger than 50 years of age (2.5% versus 2.0%). A separate analysis of the Stockholm and Oslo trials, which evaluated mastectomy with radiation therapy, was included in this meta-analysis and showed that the increase in non-breast cancer deaths was related to an increase in cardiac mortality, seen in women with cancers of the left breast who had large volumes of the myocardium included in the radiation portals. Two population-based analyses have also revealed an increase in cardiac mortality primarily in women with cancers of the left breast. One analysis of 206,523 women in the Surveillance, Epidemiology, and End Results (SEER) database, revealed that the overall relative risk for fatal myocardial infarction in women with cancers of the left breast was 1.17 (95% CI, 1.01-1.36)6 However, in comparison to the meta- analysis, this risk was seen primarily in women younger than 60 years of age (relative risk =1.98, 95% CI, 1.31-2.97). The second analysis, of 54,617 breast cancer patients reported to the Swedish Cancer Registry, revealed a higher mortality due to myocardial infarction in women with cancers of the left breast versus cancers of the right breast (relative risk= 1.09, 95% CI, 1.02-1.17).7 No overall differences in mortality were seen. Limitations of these 2 analyses were that radiation treatment, dose, fraction, and technique information were not documented. Between 1982 and 1990, the Danish Breast Cancer Cooperative Group performed 2 randomized trials (82b and 82c) in 3083 women at high risk for breast cancer recurrence (node-positive, T3 NO, or skin or pectoral fascial involvement) comparing mastectomy and adjuvant systemic therapy (CMF for premenopausal or perimenopausal women, and tamoxifen for postmenopausal women) with or without radiation therapy to the chest wall, periclavicular nodes, axilla, and ipsilateral internal mammary nodes.8 Retrospective analysis showed that the actuarial cumulative incidence of morbidity and mortality from ischemic heart disease and acute myocardial infarctions increased over time, with no significant difference between the radiation and no radiation groups at 12 years (mortality in all patients from ischemic heart disease was 0.8% with radiation and 0.9% without). Subset analysis revealed no statistically significant differences in cardiac morbidity or mortality according to tumor laterality (left versus right) and menopausal status. However, differences of the magnitude observed in the SEER and the Swedish Cancer Registry studies could not be excluded because of the smaller sample size of the Danish trials.

It will be important to determine whether this potential cardiac mortality can be modified with technical improvements, better definitions of target volumes, and limitation of cardiac volume in the radiation portals. In reference to technique, a single institution reported no statistically significant increase in cardiac mortality for women with lesions of the left breast in a series of 745 patients irradiated after breast-conserving surgery and followed for 12 years. Long-term, large scale studies of modern radiotherapeutic techniques combined with current, aggressive chemotherapeutic regimens (doxorubicin and taxol) may be necessary to better define the benefits and risks of current combined- modality therapiesin the post-mastectomy and breast-conservation setting.9

Lymphedema consequent to cancer management remains a major quality-of-life concern for breast cancer patients. Single-modality treatment of the axilla (surgery or radiation) is associated with a low incidence of arm edema. Axillary radiation therapy can increase the risk of arm edema in patients who received axillary dissection from 2% to 10% with dissection alone to 13% to 18% with adjuvant radiation therapy.10-12

Radiation injury to the brachial plexus following adjuvant nodal irradiation is a rare clinical entity for breast cancer patients. In a single institution study using current radiation techniques, 449 breast cancer patients treated with postoperative radiation therapy to the breast and regional lymphatics were followed for 5.5 years to assess the rate of brachial plexus injury. The diagnosis of such injury was made clinically with computerized tomography to distinguish radiation injury from tumor recurrence. When 54 Gy in 30 fractions was delivered to the regional nodes, the incidence of symptomatic brachial plexus injury was 1.0%, compared to 5.9% when increased fraction sizes (45 Gy in 15 fractions) were used.13

Table 1 The risk of recurrence outside the tumor bed ("elsewhere breast failure") from patients who underwent lumpectomy alone versus lumpectomy plus whole-breast irradiation from the four major prospective randomized trials

Table 2 The risk of recurrence outside the tumor bed ("elsewhere breast failure") from patients who underwent lumpectomy alone from several large retrospective trials

The rate of second malignancies following adjuvant radiation therapy is very low. Sarcomas in the treated field are rare, with the long-term risk of 0.2% at 10 years.14 One report suggests an increase in contralateral breast cancer for women younger than 45 years of age who have received chest wall irradiation after mastectomy.15 There is no increased risk of contralateral hreast cancer for women 45 years of age and older who receive radiation therapy. In nonsmokers, the risk of lung cancer as a result of radiation exposure during treatment is minimal when current dosimetry techniques are used. Smokers, however, may have a small increased risk of lung cancer in the ipsilateral lung.17

The rationales for supporting partial hreast irradiation are below.

As shown in the Tables 1-3, about 75-90% of local recurrence after lumpectomy alone occurs in the tumor bed region, and 80-90% of local recurrence after lumpectomy and whole breast irradiation occurs in the tumor bed region. Since the major effect of breast irradiation is to reduce the risk of recurrence in the tumor bed region, and whole breast, irradiation does not affect failure beyond the tumor bed region ("elsewhere breast failure").

Table 3 Early initial results (local control and cosmesis) for accelerated partial breast irradiation are similar to whole-breast irradiation. All these studies employed interstitial brachytherapy technique

Figure 1. The conventional whole-breast irradiation treats more than just the hreast, it covers the underlying chest wall, lung, and heart.

By treating part of the breast, the irradiated volume of normal structures such as uninvolved breast, lung, chest wall, and heart will be reduced; hopefully, this would translate into lesser risk of side effects from the radiation.

By treating a smaller volume of the breast, one can accelerate the treatment course; hence, it is more convenient for patients. This convenient factor is important for patients who live far away from the radiation therapy center, who have difficulty with transportation, or who have a very busy life style (Figure 1).

SUPPORTING DATA FOR BREAST BRACHYTHERAPY

Over the past 10 years, investigators from North American and Europe have looked into a shorter-course of breast irradiation to a smaller volume. One approach is to use interstitial brachytherapy to treat the lumpectomy site with a small margin over a course of 1 week with two treatments given per day. The treatment usually begins 2-3 days after the catheter placement, and continues for 1 week. This partial breast irradiation with accelerated fractionation using multiple catheters (catheter-based brachytherapy) was first done in the US more than 10 years ago by Dr. Robert Kuske. There are multiple phase I-II studies with hundreds of patients showing similar efficacy and cosmesis compared with whole-breast external beam irradiation for a selected group of patients. Initial experiences with breast brachytherapy utilized multiple catheters or needles, and these required special training and experience.

Recently, a new device, called MammoSite, was developed. The Mammosite is a new device with a single catheter centered within an inflatable balloon, which is supposed to fit inside the lumpectomy cavity (balloon-based brachytherapy). The advantages of the Mammosite are that it can easily be placed in the patient breast, it appears less invasive on the breast, and the training is simple.

BREAST BRACHYTHERAPY ELIGIBILITY

The American Brachytherapy Society recently published its recommendations.18 Accelerated partial breast irradiation is appropriate for a very selected group of patients, who meet all the following criteria:

* All patients should be appropriate candidates for standard BCT.

* At least 45 years old.

* Invasive ductal or variants (medullary, papillary, colloid (mutinous), tubular histologies). No lobular or inflamatory histology.

* Unifocal breast cancer (no multifocal or multicentric disease).

* Small tumor, not more than 3 cm in size.

* Node negative and no evidence of distant metastasis.

* Negative microscopically-assessed surgical margins.

* No extensive intraductal component or diffuse suspicious microcalcifications.

Patient selection criteria are critical and necessary to assure a successful treatment outcome. These conservative criteria are chosen to minimize the risk of microscopic disease outside the treatment area and avoid potential acute and long-term toxicities.

BREAST BRACHYTHERAPY PROCEDURE

Interstitial (catheter-based) technique

Interstitial brachytherapy, that utilizes multiple catheters or needles that deliver the radiation, was used in all the previously- mentioned studies forming the supporting data for breast brachytherapy. The major advantage of interstitial technique is that it can customize the three-dimensional dose distribution to complex target volume and shape.

At Scripps Clinic, we have performed interstitial brachytherapy for the last two years with about 70 patients. At a rough estimate, about 30% of the patients with early stage breast cancer seen in consultation are candidates for breast brachytherapy. When the option is presented to the patient, about half of the number of patients usually want to proceed with the procedure. To be eligible for breast brachytherapy, patient must meet all previously- mentioned criteria. There is also consideration of tumor/breast geometry. The tumor also must have a certain location in the breast; it can't be too close to the skin, the nipple, or the chest wall. The patient's breast size is also a consideration. After lumpectomy on a small breast, there is not much tissue left to implant the catheters (Figure 2).

The catheters are implanted at the time of breast conserving surgery. After the lumpectomy and sentinel lymph node biopsy are done, and the pathology is cleared to meet the criteria; the implant is to performed with the lumpectomy cavity open. Typically, two or three planes of catheters are used (Figure 3).

Figure 2. At Scripps, the catheters are implanted at the time of breast conserving surgery. This particular patient had bilateral breast implants.

The catheters are very small, flexible plastic tubes, like tiny straws. The diameter is 6 french (1.6 mm or about the size of a toothpick), and they're usually about 20 cm long. Most of the catheters are inside the breast, and about 5-7 cm is outside the breast. The lumpectomy cavity is closed after all catheters are implanted. The patients then undergo a CT scan of the breast without contrast for treatment planning purpose. The computer software is used to locate 3-D positions of all the catheters and to optimize the dwelling time of the high-dose rate (HDR) Iridium-192 source on each of the catheters (Figure 4).

The HDR source is 5 mm in length, and there are about 10-30 dwelling positions on each catheter. The objectives of the optimization process are to weigh the dwelling positions to achieve as uniform dose distribution to the target volume as possible while minimizing the dose to the rest of the breast, skin, chest wall, lung, and heart. Due to multiple dwelling positions and catheters, the radiation oncologist and medical physicist can customize the dose distribution, and select the "best" plan that meets the objectives. The standard dose of 3400 cGy in 10 fractions is prescribed to the 100% isodose line. The 100% isodose should cover at least 90-95% of the target volume, while keeping the hot spot or the volume of 150% isodose less than 25% of the target volume and keeping the dose away from the skin and chest wall (Figure 5).

Figure 3. Usually, two or three planes of catheters are used.

Figure 4. CT scan is used to locate the 3-D location of the catheters and to optimise the dose distribution. This 3-D reconstruction shows the catheters (in blue) in the left breast relative to dose distrihution (in red) and the left lung (in yellow) and heart (in gray).

The treatment typically begins about 2-3 days after the catheter implant. This allows for the patient to recover from the surgery, time for the treatment planning process, and final clearance from the pathologist. We prefer the final margin to be clear at least 2 mm for both invasive and non-invasive components. The margins are assessed intra-operatively by the pathologist and also by plain radiograph of the specimen. Ofthe 50 patients, one had to have the catheters removed due to the positive margin; that patient later underwent re-excision and re-implant of the catheters (using the same skin exit and entrance sites) one week after; a second patient had diffuse positive margins, and she later underwent mastectomy due to her small breast size.

The patient receives two treatments per day at about 6-hour intervals, and a total of ten treatments will be given over 5 working days. The treatment lasts about 10-15 minutes, and each treatment delivery is performed by a nurse, medical physicist, and radiation oncologist. The catheters are connected to the HDR source chamber via the transfer tubes. The radiation is delivered using a high-dose rate Iridium-192 source, which is a very powerful radioactive seed connected to a cable attached to a machine driven by a computer (Figure 6).

The catheters stay in the breast for a total of 9-10 days. Despite the invasive appearance of the implant, the catheters are very well tolerated in most patients. Most patients use over-the- counter pain medication, and few require a mild narcotic such as Vicodin. At the end of the last treatment, the catheters are removed in the clinic. The removal is very simple and takes about two minutes with minimal discomfort to the patient. The holes where the catheters were in the breast take about three or four days to close up (Figures 7 and 8).

Intracavitary (balloon-based) technique

The MammoSite device is an intracavitary device, which consists of a single catheter centered in a balloon. The balloon can be inflated to variable sizes. The catheter is implanted into the tumor resection cavity, either at the time of lumpectomy or up to 10 weeks after surgery. Catheter placement is performed either during the surgical procedure under general anesthesia or in an outpatient procedure room under local anesthesia. The MammoSite catheter is inserted into the surgical cavity through a separate pathway created by a trocar, or via the lumpectomy scar. The MammoSitevfi catheter is inflated with saline and contrast agent to allow the surrounding tissue to conform to the balloon, the exit site is dressed, and the patient is sent home (Figure 9).

Once the patient has sufficiently recovered from surgery, radiation therapy is provided on an outpatient basis. Standard protocol for primary radiation therapy that was followed in the clinical study includes two treatments per day, for 5 days, to deliver the prescribed radiation dose of 3400 cGy in 10 treatments. When used as a boost with external beam radiation, standard protocol with the MammoSite RTS includes two treatments per day, for 1 day. When radiation therapy is concluded, the balloon is deflated and the MammoSite catheter is removed (Figure 10).

Figure 5. Treatment planning software allows individually weighted dwelling times for each catheter to assure dose uniformity and minimize radiation exposure to the skin and underlying structures.

Figure 6. The catheters are connected to the HDR source chamber via the transfer tubes.

Figure 7. The breast after 10 days from the removal of the catheters.

Figure 8. The breast after 6 months from the brachytherapy.

Figure 9. The MammoSite system (Courtesy of Proximo Therapeutics, Inc, Alpharetta, GA).

The advantages of the Mammosite technique over the catheter- based technique are as follows: (1) appearance of Mammosite is much less intimidating to patients and their family; (2) the placement of the Mammosite is much easier and requires less training. This leads to wider acceptance by radiation oncologists to implement this in their practice.

However, there are several disadvantages of the Mammosite.

Figure 10. The delivery of intracavitary brachytherapy with the MammoSite RTS system.

* Firstly, the catheter-based technique is applicable to a wider range of patients. A good proportion of patients are not qualified for the Mammosite due to the non-conformity of the balloon to the cavity or to the close proximity of the balloon to skin and to the chest wall. Mammosite is applicable for a subset of patients who are candidates for breast brachytherapy, who have a small tumor (< 2 cm), the lumpectomy cavity is not close to the chest wall or skin, and the cavity shape conforms to the balloon.

* Secondly, the dose uniformity and conformity is better for the catheter-based technique since there are multiple catheters which can be used in the optimization process. The Mammosite has a single catheter, so there is not much optimization with this device. Furthermore, since the Mammosite prescribes a dose at 1 cm from the surface of the balloon, there is a larger dose gradient at the balloon surface to the prescription isodose typically in the range of 200-250%.

* The Mammosite is a newer device; there is much less data and a shorter follow-up. All previously mentioned data utilize the catheter-based technique. At the time of this writing, there was only a single phase 1 study for about 50 patients published for Mammosite.

THE PROS AND CONS OF ACCELERATED BREAST BRACHYTHERAPY

Disadvantages of breast brachytherapy compared to standard external beam radiotherapy.

Although breast brachytherapy has some advantages over the standard external beam whole breast irradiation over shorter radiation course and smaller treatment volume, there are several disadvantages.

* The published follow-up data are short (about 5 years) in a handful of phase I-II non-randomized studies; with whole breast irradiation, there are many long-term (20 years) phase III prospective randomized studies. Phase III studies comparing whole- breast irradiation versus accelerated partial breast irradiation are currently being planned.

Table 4

* Breast brachytherapy is more invasive due to the catheters in the breast. There is short-term discomfort and risk of infection. Whole breast radiation is noninvasive and well tolerated.

* Breast brachytherapy is very dependent on the skill and technique. If you have a proper implant, you have a good outcome and good cosmesis. If you have a suboptimal implant, you have a bad outcome and/ or poor cosmesis.

* Whole breast irradiation is applicable for almost all stages of breast cancer and it can be used for patients of all ages. It is much less work for the radiation oncologists and medical physicist. Brachytherapy is more labor-intensive.

Advantages of partial breast brachytherapy over standard whole- breast irradiation.

* The overall treatment time with partial breast brachytherapy is reduced to 1 week compared to a 6-7 week course of daily external beam radiotherapy. This is convenient to elderly patients, patients with a busy working schedule, patients living far away from the radiation clinic, and patients with limited transportation. This advantage can possibly increase the number of patient selecting breast conserving therapy instead of mastectomy.

* Partial breast irradiation can significantly reduce radiation dose to the lungs, heart, rib (bone marrow), and contralateral breast, uninvolved ipsilateral breast. This leads to less morbidity for patients with a large breast, limited lung capacity, and who are at high risk of heart disease.

* Some high risk patients who need both chemotherapy and radiation therapy as well as accelerated breast brachytherapy experience no delays in other treatments such as chemotherapy. There is controversy regarding the sequence of chemotherapy or radiotherapy. If chemotherapy is given first, then the standard radiation is delayed for 4-6 months after surgery, and this could potentially lead to a high risk of local recurrence. If the standard radiation is given before the chemotherapy, then it would delay the chemotherapy for about 2-3 months; and this could potentially lead to a higher risk of distant relapse. In patients who do not need treatment for lymphatics, accelerated partial breast brachytherapy completes the requirement for adjuvant radiation less than 2 weeks after the surgery, and then the patient can start the chemotherapy without delay.

CONCLUSION

The accelerated partial breast brachytherapy is the only new treatment technique in radiation therapy for breast cancer in the last five decades. Its main advantages are the convenience of a shorter treatment course and less radiation to the normal structures. It still requires long-term follow-up for maturity of the clinical data to support its claim of similar local control and cosmesis, and less long-term morbidity. The success of this technique relies significantly on the careful patient selection and proper technique. The breast brachytherapy will never replace the standard whole-breast irradiation, but it provides an alternative to some patients, who would otherwise choose mastectomy or refuse post- lumpectomy irradiation. Hopefully, this would increase the number of patients to preserve their breast without compromising the local control and survival.

REFERENCES

1. Nattinger AB, Hoffmann RG, Knewsel RT, Schapira MM Relation between appropriateness of primary radiation therapy for early- stage breast carcinoma and increased use of breast-conserving surgery. Lancet 2000;356:1148-1153.

2. Fisher B, Bryant J, Dignam JJ, et al. Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less. J Clinic Oncol 2002;20:441-4149.

3. Liljeegren G, Holmberg L, Bergh J, et al. 10 year result after sector resection with or without postoperative radiotherapy for stage I breast cancer: a randomized trial. J Clin Oncol 1999;17:2326- 2333.

4. Lingos TI, Recht A, Vicini F, et al. Radiation pneumonitis in breast cancer patients treated with conservative surgery and radiation therapy, int J Radiat Oncol Biol Phys 1991;21(2):355-60.

5. Early Breast Cancer Trialists' Collaborative Group. Favourable and unfavourable effects on long-term survival of radiotherapy for early b\reast cancer: an overview of the randomised trials. Lancet 2000;355(9217):1757-70.

6. Paszat LF, Mackillop WJ, Groome PA, et al. Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries. J Clin Oncol 1998;16(8):2625-31.

7. Rutqvist LE, Johansson H. Mortality by laterality of the primary tumour among 55,000 breast cancer patients from the Swedish Cancer Registry. Br J Cancer 1990;61(6)-.866-8.

8. Hjris I, Overgaard M, Christensen JJ, et al. Morbidity and mortality of ischaemic heart disease in high-risk breast-cancer patients after adjuvant postmastectomy systemic treatment with or without radiotherapy: analysis of DBCG 82b and 82c randomised trials. Radiotherapy Committee of the Danish Breast Cancer Cooperative Group. Lancet 1999;354(9188):1425-30.

9. Harris JR, Halpin-Murphy P, McNeese M, et al. Consensus Statement on postmastectomy radiation therapy. Int J Radiat Oncol Biol Phys 1999;44(5):989-90.

10. Meek AG. Breast radiotherapy and lymphedema. Cancer 1998;83(12 Suppl American):2788-97.

11. Larson D, Weinstein M, Goldberg I, et al. Edema of the arm as a function of the extent of axillary surgery in patients with stage I-II carcinoma of the breast treated with primary radiotherapy, lnt J Radiat Oncol Biol Phys 1986;12(9):1575-82.

12. Swedborg I, Wallgren A. The effect of pre- and postmastectomy radiotherapy on the degree of edema, shoulder-joint mobility, and gripping force. Cancer 1981;47(5):877-81.

13. Powell S, Cooke J, Parsons C. Radiation-induced brachial plexus injury: follow-up of two different fractionation schedules. Radiother Oncol 1990;18(3):213-20.

14. Taghian A, de Vathaire F, Terrier P, et al. Long-term risk of sarcoma following radiation treatment for breast cancer. Int J Radiat Oncol Biol Phys 1991;21 (2): 361-7.

15. Boice JD Jr, Harvey EB, Blettner M, et al Cancer in the contralateral breast after radiotherapy for breast cancer. N Engl J Med 1992;326 (12):781-5.

16. Storm HH, Andersson M, Boice JD Jr, et al. Adjuvant radiotherapy and risk of contralateral breast cancer. J Natl Cancer inst 1992;84(16):1245-50.

17. lnskip PD, Stovall M, Flannery JT. Lung cancer risk and radiation dose among women treated for breast cancer. J Natl Cancer Inst 1994;86(13):983-8.

18. Arthur DW, Vicini FA, Kuske RR, et al. Accelerated partial breast irradiation: an updated reported from the American Brachytherapy Society. Brachytherapy 2003;2:124-130.

Huan B. Giap

Division of Radiation Oncology, Scripps Clinic, 10666, North Torrey Pine Rd, La Jolla, CA 92037, USA

Copyright CRC Press Dec 2004

Source: Women's Oncology Review

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