|Year : 2014 | Volume
| Issue : 4 | Page : 889-895
Clinical and cosmetic results of breast boost radiotherapy in early breast cancer: A randomized study between electron and photon
Soumiya Sampath Rajan1, Suresh Chander Sharma1, Narendra Kumar1, Ritesh Kumar1, Gurpreet Singh2, Rajender Singh2, Parsee Tomar3
1 Department of Radiotherapy, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Medical Physics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||9-Jan-2015|
Department of Radiotherapy and Regional Cancer Centre, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
Source of Support: None, Conflict of Interest: None
Introduction: Breast-conserving surgery followed by radiation therapy (RT) to the intact breast is now clearly established as the most acceptable strategy for women with early-stage invasive breast cancer. Recommended techniques for radiotherapy is whole breast irradiation (WBI) followed by boost to the tumor bed.
Aims: The aim of this study is to compare the modalities of three-dimensional conformal RT (3DCRT) and electron beam therapy as boost in post-lumpectomy patients of early stage breast cancer, following WBI.
Materials and Methods: The study comprised of selecting 50 patients of early-stage post-lumpectomy breast cancer. Each patient was initially treated by WBI (40 Gy in 16 fractions) and then followed by tumor bed boost (16 Gy in 8 fractions) with either electron beam therapy or with photon (3DCRT), 25 patients in each arm. Patients were evaluated regularly for acute and chronic radiation toxicities, cosmesis, and pattern of failure. Dosimetric comparison of the plans was also done.
Results: Median age of the patients was 42 years with 66% being premenopausal. Median duration of follow-up was 23 months. In arm A (electrons), two patients had grade III-IV reactions at treatment completion with one patient required RT interruption. Whereas, in arm B (3DCRT), five patients had grade III-IV reactions at treatment completion with three patients required RT interruption. At 6 months and 2 years follow-up, both the arms had almost similar skin, subcutaneous toxicity, and cosmetic score. At the end of 2 years, there were totally four failures among 50 patients, with one locoregional failure in both arms (4%). Dosimetric analysis revealed that conformality (radiation conformity index (RCI)), dose homogeneity index (DHI) and planning target volume (PTV) coverage was significantly better in 3DCRT boost plans. Organs at risk (OAR) dosimetry also revealed significant decrease in ipsilateral lung and heart doses with 3DCRT plans in which tangential or oblique fields were used; and whereas in electron beam, only single direct fields were used.
Conclusions: Both electrons and 3DCRT can be used for boost planning to the tumor bed in post-lumpectomy patients. Though there was slightly increased acute skin toxicity with 3DCRT photon which led to interruption of therapy, overall cosmesis at 2 years is similar in both modalities. 3DCRT boost is a better option than electrons dosimetrically, considering the fact that conformality; PTV coverage and OAR dosimetry were superior with photons. Thus in centers where electron beam therapy is not available, 3DCRT photon can be used effectively for tumor bed boost.
材料与方法：研究包括50例早期乳腺癌术后患者。每例患者最初的治疗照射（40 Gy/16次），瘤床加量（16 Gy/8次），用电子束治疗或光子（3DCRT），每组25例。定期评估患者的急性和慢性副作用，美观和失败模式。同时做了剂量学比较。
Keywords: 3DCRT, boost, breast cancer, electron
|How to cite this article:|
Rajan SS, Sharma SC, Kumar N, Kumar R, Singh G, Singh R, Tomar P. Clinical and cosmetic results of breast boost radiotherapy in early breast cancer: A randomized study between electron and photon. J Can Res Ther 2014;10:889-95
|How to cite this URL:|
Rajan SS, Sharma SC, Kumar N, Kumar R, Singh G, Singh R, Tomar P. Clinical and cosmetic results of breast boost radiotherapy in early breast cancer: A randomized study between electron and photon. J Can Res Ther [serial online] 2014 [cited 2019 Nov 14];10:889-95. Available from: http://www.cancerjournal.net/text.asp?2014/10/4/889/138228
| > Introduction|| |
In a general radiation oncology practice, breast cancer typically comprises approximately 25% of the total patient caseload.  Surgery is the primary modality of treatment. Radical mastectomy remained the mainstay of surgical therapy up to the 1970s.  Breast-conserving surgery followed by radiation therapy (RT) to the intact breast is now clearly established as the most acceptable standard of care for the majority of women with early stage invasive breast cancer. ,,,,,,, Not only the disease-free and overall survival rates after such treatment are comparable with those of patients treated by mastectomy; but in addition, breast-conserving therapy offers an obvious cosmetic advantage that may enhance quality of life and lead to less psychological and emotional treatment-related distress.
Recommended techniques for breast-conservation treatment are local excision of the primary tumor, preferably with clear margins, axillary lymph node dissection, and breast irradiation (WBI), usually with a boost (10-20 Gy). ,,, There are several randomized, controlled trial data to demonstrate the local control and survival benefit of this treatment modality. The European Organisation for Research and Treatment of Cancer (EORTC) 'boost versus no boost' randomized trial clearly demonstrated a significantly better local control rate with the higher radiotherapy dose, especially in women younger than 50 years of age. 
Interstitial implant or electron beam therapy are standard modalities for boost.  More recently, techniques using computed tomography (CT)-based three-dimensional planning have been used for breast boost RT with photons. 
Interstitial implant is an invasive procedure, while electrons are not universally available in community settings. Three-dimensional conformal RT (3DCRT) photon is an easier technique for breast boost RT and this study compares the modalities of 3DCRT vs electron beam therapy as boost in post-lumpectomy patients of stage I and II breast cancer, following whole breast irradiation (WBI) in terms of acute and chronic radiation toxicities, cosmesis, pattern of failure, and dosimetric parameters.
| > Materials and methods|| |
Fifty patients of histologically proven post-lumpectomy cases of early carcinoma breast (stage I and II) were enrolled in this study between July 2010 and March 2011. All patients had unicentric primary breast cancer with invasive ductal histology. Patients who have received neoadjuvant chemotherapy (NACT) or adjuvant chemotherapy were also included in the study. The patients were randomized on the basis of computer-generated random numbers. Randomization to both the boost technique was done during the 1 st week of whole breast external beam RT. This was done to decrease any potential bias due to the physicians' awareness of the allocation group that might have influenced the cosmetic evaluation at baseline.
Simulation and treatment planning
A planning CT scan was performed for each patient. The patients were positioned on a breast board with sternum parallel to the table, and the ipsilateral arm abducted above the head. Before the CT scan, skin marks were placed to enable the patient repositioning during treatment. Radioopaque markers were placed over the scar to guide in locating lumpectomy cavity on CT images. Then CT images were transferred to the treatment planning system (Varian TM Eclipse 8.6). Each patient was initially treated by WBI (dose of 40 Gy in 16 fractions at 5 fractions per week), , by two tangential fields and then followed by tumor bed boost with electron beam therapy in one arm and 3DCRT in another arm, boost dose of 16 Gy in 8 fractions at 5 fractions in a week, being same in both arms.
The gross tumor volume (GTV) was defined by lumpectomy cavity contoured on each CT slice. In few cases, tumor bed clips defined the extension of the tumor bed. When surgical clips were not present, preoperative mammography and ultrasound data, surgical description, and postoperative seroma cavity or fibrosis in the CT scan were used for lumpectomy cavity definition The clinical target volume (CTV) consists of GTV uniformly expanded in three dimensions by 1 cm; however, the volume was constrained to lie 5 mm within external contour and up against the pectoralis major muscles. To account for treatment set-up uncertainties and breathing motion, the boost planning target volume (PTV) was calculated from the CTV using uniform three-dimensional expansion of 0.5 cm. 3DCRT plans were planned with 6 MV photons with two minitangents and wedges, while electron plans used a single direct electron field with energy according to the depth and coverage of PTV. The common electron energy used was 6 and 9 MeV.
Plans were evaluated both quantitatively (analyzing dose volume histograms) and qualitatively (by visually inspecting isodose curves). Plans were inspected for conformity, doses delivered to target and organs at risk (OAR) and comparisons done between 3DCRT boost plans and electron beam boost plans. Patients in both the arms were evaluated for local tumor control, pattern of failure, radiation toxicities both acute as well as late, and dosimetric parameters. Follow-up of patients was initially after 4 weeks post-RT. Then 2-monthly for 6 months and then 4-monthly. The Radiation Therapy Oncology Group (RTOG) scores were used for assessment of skin and subcutaneous toxicities and cosmetic outcome assessed by using Harris and Van Limbergen scale.  All assessment and evaluation was done by a single physcian to exclude any interobsever bias.
The primary objective of this study were comparison of acute toxicities, late toxicities, and cosmetic outcomes between 3DCRT photon and electron as breast boost RT; while secondary objectives were patterns of failure and dosimetric evaluation.
The principle end point of the study was an analysis of acute and late radiation toxicities, cosmetic score analysis, local control, and dosimetric comparisons of the electron and 3DCRT photon boost arm. Skin, subcutaneous toxicity, and cosmetic assessment was done before treatment and then in regular follow-up of the study. Descriptive statistics including mean and standard deviation was obtained for all variables. A Student t-test was used to compare the dosimetric parameters. P values of < 0.05 were taken as significant. All tests were performed using Statistical Package for the Social Sciences (SPSS) version 12.0.
| > Results|| |
The patient characteristics are summarized in [Table 1]. Median age of these patients was 42 years and median duration of symptoms was 6.4 months. There were 33 premenopausal patients and 17 postmenopausal patients. Twenty-four (48%) of the tumors were in the right breast and 26 (52%) were in the left breast. The mean follow-up time was 23 months.
Early skin toxicity [Table 2]
During assessment at 1 month post-radiation, grade I reactions were seen in 18 of electron boost patients (72%) and in 16 of 3DCRT photon patients (64%). Grade III-IV skin reactions were observed in two (8%) of electron boost patients and five (20%) of 3DCRT boost patients which led to treatment interruption in one of the electron boost patient and three of 3DCRT photon boost patients, indicating slightly higher toxicity in the 3DCRT boost patients at early stage.
Late skin and subcutaneous toxicity [Table 3]
At the end of 6 months post-radiation, grade I skin reaction were observed in 16 patients (64%) of both electron and 3DCRT boost arms. Similarly, grade II reactions were seen among nine patients (36%) in both arms, thus indicating similar late skin toxicities.
At the end of 1 year follow-up, grade I skin reactions were seen in 24 patients (96%) of the electron boost arm and in 23 patients (92%) of 3DCRT boost arm. And grade II skin reactions were observed in one (4%) and two patients (8%), respectively, with no grade III/IV reactions. At 2 years follow up, grade I reactions were seen in 23 patients (92%) of the electron boost arm and in 24 patients (96%) of 3DCRT boost arm. And grade II skin reactions were observed in two (8%) and one patient (4%), respectively, thus depicting almost similar results in both groups.
During assessment at 6 months post-radiation, grade me subcutaneous toxicity was observed in 16 patients (64%) of electron boost arm and in 17 patients (68%) of 3DCRT boost arm. Grade II subcutaneous toxicity was observed in nine (36%) and in seven patients (36%), respectively. Grade III subcutaneous toxicity was observed in only one (4%) 3DCRT boost patient and no grade IV toxicity.
At the end of 1 year follow-up, grade I subcutaneous toxicity was observed in 15 patients (60%) of electron boost arm and in 16 patients (64%) of 3DCRT boost arm. Grade II subcutaneous toxicity was observed in 10 (40%) and eight patients (32%), respectively. Grade III subcutaneous toxicity was observed in only one among the 3DCRT boost patient (4%). At 2-years follow-up, grade I subcutaneous toxicity was observed in 18 patients (72%) of electron boost arm and in 20 patients (80%) of 3DCRT boost arm. Grade II subcutaneous toxicity was observed in seven (28%) and five patients (20%), respectively, thus improving with time.
Cosmetic score [Table 4]
At 1 month follow-up, good (grade I) cosmetic score was observed in eight patients (32%) of electron boost arm and in six patients (24%) of 3DCRT boost arm. Moderate (grade II) cosmetic score were seen in 13 (52%) of electron boost patients and in 14 (56%) of 3DCRT boost patients. Bad score (grade III) were seen in four (16%) and five (20%) patients, respectively.
At 6 months follow-up, excellent cosmetic score was observed in one (4%) of the 3DCRT boost patient. Good (grade I) cosmesis was observed in 11 patients (44%) of electron boost arm and in 13 patients (52%) of 3DCRT boost arm. Moderate (grade II) cosmetic score were seen in 14 (64%) and 10 (40%) patients, respectively and bad cosmesis was seen in only one of the 3DCRT boost arm.
At the end of 1 year follow up, excellent cosmetic score was observed in two patients (8%) of electron boost arm and in three (12%) of the 3DCRT photon boost patients and good (grade I) cosmetic score was observed in 13 patients (52%) of both the arms. Moderate (grade II) cosmetic score were seen in 10 (40%) of electron arm and eight (36%) patients of 3DCRT arm and bad cosmesis was seen in only one (4%) 3DCRT boost patient.
At 2 years follow-up, excellent cosmetic score was observed in four patients (16%) of electron boost arm and in five (20%) of the 3DCRT boost patients and good (grade I) cosmetic score was observed in 16 (64%) and 15 patients (60%), respectively. And moderate (grade II) cosmetic score were seen in five (20%) patients of both arms and no bad cosmesis was seen depicting improvement of cosmesis with time.
Dosimetric evaluation [Table 5]
The mean PTV coverage was significantly better with 3DCRT photon plan (P = 0.05). There was an increase in mean dose received by contralateral breast and lung in 3DCRT photon plans when compared with electron plan, and this has statistical significance (P = 0.04 and 0.041, respectively). However, there was a significant decrease in mean doses received by ipsilateral lung and heart in left-sided lesions in 3DCRT boost plan when compared with electron boost plan (P = 0.003).
Pattern of failure
At the end of 2 years follow-up, there were totally four failures among 50 patients, two in each arm. In the electron arm, one patient had both local in-field recurrence and systemic failure in the form of liver metastasis. And the second patient failed at distant site, malignant pleural, and pericardial effusion.
In the 3DCRT photon arm, one patient failed at nodal site, developed axillary nodal mass and the second patient failed at distant site, vertebral metastasis.
| > Discussion|| |
Breast-conserving surgery followed by WBI is the gold standard in the treatment of early-stage breast cancer. ,,,,,,, The concept of tumor bed boost originated from the observation that the vast majority of ipsilateral breast tumor recurrences (IBTR) arose in the vicinity of the original index lesion (50-60%). The landmark study; the EORTC 22881-10882 trial, 1989-1996; detected 5% improvement in 10-year survival. 
Randomized and controlled studies have shown the impact that the boost has on local tumor control. ,,, The local failure rates have been observed in whole breast radiotherapy (WBRT) arm versus WBRT + boost arm in Lyon trial  (4.5 vs 3.6%), EORTC trial  (10.2 vs 6.2%), and Budapest trial  (15.5 vs 6.7%). Thus, various boost studies have reported 10-20% relative reduction in local failure.
Young females below the age of 50 years are routinely recommended to receive tumor bed boost. , Additional risk factors for local recurrence can be big tumor size, close surgical margins, high grade invasive ductal or in situ ductal tumors, high mitotic index, hormone receptor negative tumors (contraindication for hormonal therapy), and presence of extensive intraductal component.
A number of trials have studied and compared the different boost modalities in the past, electrons and interstitial implant boost being the standard among them.  In case of boost with electrons, fields defined on the basis of clinical details and scar have been found to be erroneous in several studies. , Hence, the dimensions as well as depth for tumor bed boost should be determined either by fluoroscopy or CT combined with surgical clips, or an ultrasound. ,, The electrons have limited role in patients with large breasts and tumors situated at a depth, that is, closer to heart (on left) and lungs and in folds. 
Interstitial implant is an invasive procedure associated with pain, is technically challenging and is not universally available in community settings. , The overall cosmesis is commonly compromised with formation of scars at the entry and exit sites of interstitial needles or tubes.
3DCRT with photon is an easier technique for breast boost RT and is an noninvasive procedure.  The exact site of lumpectomy cavity can be delineated easily with the help of surgical clips and architectural changes. The planning and field arrangements can be done with better conformity and homogeneity along with sparing of normal OAR.
In this study, we have compared the standard electron boost and the 3DCRT photon boost in terms of acute and late radiation toxicities, cosmetic score, patterns of failure, and dosimetric analysis.
Acute skin toxicity analysis showed slightly more toxicity in photon arm with grade IV skin toxicity in 12% of 3DCRT photon boost patients leading to treatment interruption in three patients; whereas, only 4% grade IV skin reactions and treatment interruption in one patient were seen in electron boost arm. But the late skin toxicity scores became almost comparable between the two arms at the end of 6 months, 1 year, and 2 years.
Grade II subcutaneous fibrosis was observed in 20% (five patients) of 3DCRT boost and 28% (seven patients) of electron boost at the end of 2 years. In a similar study of experience with 3DCRT boost only, in 77 early breast cancer patients by Kovacs et al., in Hungary depicted grade I-II breast fibrosis in 12.9% (10 cases) at the end of 4 years of follow-up.  Thus, observing our patients for further 3-4 years might result in improvement of breast fibrosis and better cosmetic score.
Good and excellent cosmetic scores were observed in 64 and 60% of 3DCRT and electron boost patients [Figure 1] and [Figure 2], respectively, and fair (moderate) cosmetic score in 32 and 40%, respectively, at the end of 1 year. Good and excellent cosmetic scores were observed in 80% patients of both arms at the end of 2 years. Similar results were observed by Kovacs et al., in the above study,  in which they reported good and excellent cosmetic scores in 88.3% and fair cosmetic score in 11.6% of 3DCRT photon boost patients at the end of 4 years follow-up. Thus, indicating the fact that breast cosmesis improves with time, post-radiation, and better appreciated in long-term follow up studies.
Dosimetric analysis revealed that conformality (radiation conformity index (RCI)) and PTV coverage was significantly better in 3DCRT boost plans. The mean RCI was 1.017 and 1.23 in 3DCRT and electron boost patients, respectively, and mean dose homogeneity index (DHI) was 0.93 and 0.91, respectively. Thus, CT-based planning of 3DCRT photon boost is superior to single direct electron field in terms of PTV coverage, target conformity, and homogeneity.
OAR dosimetry also revealed significant decrease in ipsilateral lung and heart doses with 3DCRT plans in which tangential or oblique fields were used; whereas, in electron beam where only single direct fields were used. The mean ipsilateral lung volume receiving 2 Gy, V 2Gy was calculated using dose-volume histograms (DVHs) and was 13.2% in case of 3DCRT photons and 25.9% in case of electrons.
On assessing the patterns of failure in these patients, local relapse rate was 4% in electron boost arm; and in the 3DCRT photon boost arm, no local in-field recurrence was noted at the end of 2 years and the nodal failure rate was 4%. The 2-year probability of distant metastasis free survival was 96% in 3DCRT and 92% in electron boost arm, and thus depicting no significant difference between two arms. Further long-term follow-up is required to assess failure rates with both of these boost modalities.
| > Conclusion|| |
Thus, both electron and 3DCRT photon can be used for boost planning to the tumor bed. There is slightly increased acute skin toxicity with 3DCRT photon in this study which leads to interruption of therapy; but overall skin, subcutaneous toxicity, and cosmesis at 2 years is similar in both arms. 3DCRT boost is a better option than electrons dosimetrically, considering the fact that conformality, PTV coverage was superior with former plans. Also, ipsilateral lung and heart doses were significantly reduced with 3DCRT photons. Thus, in centers where electron beam therapy is not available, 3DCRT photon can be used effectively for tumor bed boost. And regarding patterns of failure, further long-term follow-up is necessary for better appreciation of results.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]