Practical Radiation Oncology (2013) 3, e45–e53
www.practicalradonc.org
Original Report
Skin dose effects of postmastectomy chest wall radiation therapy using brass mesh as an alternative to tissue equivalent bolus Erin Healy MA a , Shawnee Anderson BA b , Jing Cui DSc c , Laurel Beckett PhD d , Allen M. Chen MD c , Julian Perks PhD c , Robin Stern PhD c , Jyoti Mayadev MD c,⁎ a
University of California, Davis, Sacramento, California Department of Mathematics, California State University, Sacramento, California c Department of Radiation Oncology, University of California, Davis, Sacramento, California d Department of Biostatistics, University of California, Davis, Sacramento, California b
Received 29 February 2012; revised 25 May 2012; accepted 29 May 2012
Abstract Purpose: The use of brass mesh as a bolus is relatively uncommon in postmastectomy chest wall radiation therapy (PMRT). This study aimed to characterize the skin dose effects of using 2-mm fine brass mesh as an alternative to the traditional tissue-equivalent bolus during chest wall PMRT. Methods and Materials: Data were collected from patients who received PMRT using brass mesh at the University of California Davis Department of Radiation Oncology between January 2008 and June 2011. Several patient characteristics including age, body habitus, and ethnicity were analyzed along with several disease and treatment characteristics to determine whether or not they had an impact on the skin reaction observed during radiation treatment. Additionally, in vivo surface dose measurements were obtained for 16 of the 48 patients (33%). Results: Forty-eight female patients aged 28-83 received PMRT using brass mesh. As expected, the severity of skin toxicity increased with subsequent doses of radiation with all patients beginning treatment with no skin reaction (National Cancer Institute scores [NCIS] = 0) and the majority of patients completing treatment with either faint to moderate erythema (n = 19, 40%, NCIS = 1) or moderate to brisk erythema (n = 23, 48%, NCIS = 2). In vivo dosimetry analysis revealed surface doses between 81% and 122% of the prescribed dose, with an average of 99% of the prescribed radiation dose and standard deviation of 10% being delivered. Conclusions: For postmastectomy chest wall radiation therapy, brass mesh is an effective alternative to tissue-equivalent bolus. The brass mesh achieved moderate erythema in the majority of patients at the end of treatment and the surface dose was validated using in vivo dosimetry. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.
Conflicts of interest: None. Sources of support: Medical student fellowship from the University of California, Davis, Sacramento, California. ⁎ Corresponding author. University of California Davis Medical Center, Radiation Oncology, 4501 X St, Sacramento, CA 95817. E-mail address: [email protected] (J. Mayadev).
Introduction Postmastectomy radiation therapy (PMRT) has been proven to increase the locoregional and overall survival of patients with locally advanced breast cancer. 1-5 The area at
1879-8500/$ – see front matter. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. http://dx.doi.org/10.1016/j.prro.2012.05.009
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highest risk for local regional recurrence is the chest wall. In fact, the target volume at risk for postmastectomy patients includes the entire soft tissue of the chest wall including residual breast tissue, surrounding skin, connective tissue, and the regional lymphatics. 3,6-9 Long-term locoregional failure rates may be as high as 40%. 10 The chest wall is a challenge to treat with radiation therapy due to its irregular surface contours, large curvature and near-surface target tissue volume. 11 Consequently the goals of postmastectomy radiation are to deliver adequate radiation to the chest wall while limiting toxicity to tissues outside of the target volume. 11 Furthermore, the risk of a skin recurrence is usually considered to be substantial. The dose at the skin for megavoltage photon treatments is influenced by the electron contamination from the flattening filter, source to skin distance, beam modifiers, and beam characteristics such as angle incidence, energy, and field size. For 6-MV photons, the depth of maximum dose (Dmax) is 1.5 cm, with the surface dose substantially lower. For opposed tangential fields, this “skin sparing” translates into a skin dose of about 80% of prescription. Often, tissue-equivalent bolus (TEB) is used during the course of PMRT to increase surface dose to the target tissue volume. 11,12 TEB contributes to the dose build-up and yields adequate dose contribution to the skin and shallow tissues. Studies have shown that surface dose is increased with the use of TEB material over the chest wall. 11 This material, however, due to its thickness and inflexibility, adds another layer of complexity to the already challenging task of treating PMRT. Due to its rigidity, air gaps are often introduced between TEB and the skin that can potentially cause a skin sparing effect in the radiation dose that is delivered to the chest wall. In addition, if TEB is to be used and subsequently discontinued, 2 treatment plans must be generated to accurately depict the patient's dose distribution during the radiation treatment course.
In 2008, the Radiation Oncology Department at the University of California, Davis (UCD) began using a fine brass mesh (Fig 1; Whiting and Davis, North Attleboro, MA) when delivering PMRT as an alternative to TEB. The enhanced dose to the skin at the skin-mesh interface is due primarily to secondary charged particles produced in the mesh. The mesh conforms to the irregular contours of the chest wall with fewer gaps better than TEB material. Furthermore, during the commission of the clinical use of brass mesh, in-house testing by our physics team showed that the mesh did not affect the dose below Dmax and that monitor units (MUs) did not change substantially with its use. As a result, the use of brass mesh reduces the complexity of accounting for a bolus in simulation and treatment planning. Surface skin reaction is important in the PMRT setting as it has been shown that local control is improved when brisk erythema or moist desquamation is achieved. 13 During treatment, the surface dose can be assessed visually by observing the reaction of the overlying skin. In addition, we have investigated surface dose measurements for patients treated with brass mesh. Although the effects of using TEB are well documented, the effects of using brass mesh to decrease the buildup depth are not as well studied. 11,12 This investigation aimed to characterize the skin changes associated with using brass mesh during PMRT at UCD from January 2008 to June 2011.
Methods and materials Patient characteristics After approval by the institutional review board at University of California Davis Medical Center, we identified patients with breast cancer who were treated with PMRT using brass mesh as a TEB between January 2008 and June 2011 at UCD. Inclusion criteria were patients with a known diagnosis of breast cancer who were treated with mastectomy followed by chest wall irradiation at UCD. These patients were then cross-referenced with the radiation oncology database to determine if brass mesh was used during chest wall irradiation and 48 patients were identified. Data for demographics, stage at diagnosis and pathology, radiation dose, fractionation, beam energy, area, surgical technique, reconstruction, chemotherapy, and side effects were extracted.
Treatment
Figure 1
Brass mesh.
All patients were treated with a mastectomy and either a sentinel lymph node biopsy or an axillary dissection. Adjuvant chemotherapy and radiation therapy were delivered based on the National Comprehensive Cancer Network practice guidelines. In those patients requiring
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chemotherapy, this was delivered prior to radiation therapy, and after the mastectomy. The type of chemotherapy delivered is seen in Table 1. Overall, 28 (58%) patients
Table 1
Brass mesh as an alternative bolus in PMRT
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received chemotherapy with doxorubicin (Adriamycin)containing regimens. Eleven (23%) patients received concurrent and adjuvant treatment with trastuzumab.
Patient characteristics
Age (y)
Hormone receptor status
Chemotherapy
Fields
Total cumulative dose (cGy)
28 33 39 40 42 42 43 43 45 46 49 50 50 51 52 52 53 53 53 53 54 54 56 56 56 59 60 60 61 61 61 67 67 69 69 69 70 70 71 72 73 74 77 77 80 81 83 83
ER +/PR+ HER2+ HER2+ ER-/PR-/HER2ER +/PR+ ER +/PR+ Unknown ER +/PR+ ER +/PR+ ER +/PR+ ER + ER +/PR+ HER2+ HER2+ ER-/PR-/HER2ER-/PR-/HER2ER +/PR+/HER2 + Unknown Unknown ER-/PR-/HER2ER +/PR+/HER2 + ER-/PR-/HER2ER +/PR+ ER +/PR+ ER + ER +/PR+ ER +/PR+ HER2+ ER +/PR+ ER-/PR-/HER2HER2+ ER +/PR+ ER +/PR+ HER2+ HER2+ ER-/PR-/HER2ER +/PR+ ER-/PR-/HER2ER-/PR-/HER2ER +/PR+ ER +/PR+ ER +/PR+/HER2 + ER +/PR+ HER2+ Unknown ER +/PR+ ER +/PR+ ER +/PR+
DXN/CYP + PTL DTX/CRB + TRB 5-FU/DXN/CYP + PTL/TRB DXN/CYP + PTL DXN/CYP + DTX + TMX DXN/CYP + PTL/BVZ Unknown DXN/CYP + PTL, DTX ddDXN/CYP + ddPTL DXN/PTL + BVZ DXN + PTL DXN + PTL DXN + PTL/TRB, CYP DXN/CYP + PTL/TRB DXN/CYP + PTL DXN/CYP + DTX DXN/CYP + PTL/TRB DXN/CYP + PLT ddDXN + PTL ddDXN/CYP + PTL DXN/CYP + PTL/TRB None DTX/CYP ddDXN/PTL CMF + DXN, DTX + CYP DXN/CYP + PTL/BVZ None DXN + PTL DXN/CYP + PTL DXN/CYP/PLT DXN/CYP + PTL/TRB, -PTL+PTL DTX or DTX/CYP DXN/PTL DTX + TRB, PTL/TRB DTX/CRB + TRB None None DTX/CYP TMX None DTX/CYP DTX/CRB/TRB + TRB ddDXN + PTL PTL/TRB, CPB/TRB None DXN/CYP + DTX TMX None
3 3 3 4 5 6 3 7 7 5 4 4 4 5 5 4 5 3 4 3 5 3 3 2 3 3 2 3 2 4 4 3 3 5 5 3 5 5 5 2 4 3 3 6 3 5 3 5
6040 5000 5000 5040 5000 5000 6000 5000 5000 5000 5040 5000 5000 5040 5000 5000 5000 5000 5000 5000 5000 5040 6000 6200 5000 5000 5000 5000 5000 4600 6000 5000 5000 6000 5040 5600 4400 5000 5040 6000 5040 6000 5000 6200 5000 6000 6000 6000
5-FU, fluorouracil; dd, double dose; BVZ, bevacizumab/Avastin; CPB, capecitabine/Xeloda; CRB, carboplatin; CYP, cyclophosphamide/Cytoxan; DTX, docetaxel/Taxotere; DXN, doxorubicin/Adriamycin; ER, estrogen receptor; HER2, human epidermal growth receptor-2; PR, progesterone receptor; PTL, paclitaxel/Taxol/Abraxane; TMX, tamoxifen; TRB, trastuzumab/Herceptin.
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Radiation treatment parameters Patients were treated with PMRT using opposed tangential 6-MV photons. During the treatment period, all fields were treated daily for 5 of 7 days per week. Additional fields or a boost were at the discretion of the treating physician. Forty-three (90%) patients received a supraclavicular field, and 17 (35%) patients received a chest wall boost. The boost was delivered without bolus using en face electron fields with electron dosimetry. Treatment planning was done without accounting for the mesh bolus because the planning system cannot model the bolus and because tests showed that doses below Dmax were unaffected by it. During the commission of the clinical use of the brass mesh, we performed relative dose measurements on water-equivalent phantom using 6× and 15× photon beams, with and without the mesh. For both energies, the dose at Dmax was within 0.4%, with and without the mesh. Further measurements showed that the dose at depths down to 10 cm varied by b 1%, therefore the same MUs can be used with the mesh as calculated without it.
Brass mesh parameters Brass mesh was overlaid on the patient's chest wall over 1 layer of pillowcase. Our group has conducted measurements using 1 layer of pillowcase versus no pillowcase and found that for electron fields, the skin dose does not change by adding a pillowcase underneath the bolus except for 6e, for which the skin dose increases by 1%. For photon fields, the skin dose increases by 1%-2% which is still minimal. Thus, a pillowcase can be used as a separation between the patient's skin and bolus material without the need to adjust
Figure 2
Conformance of the brass mesh.
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the planned MU. The therapists visualize the brass mesh on the treatment field and smooth out the wrinkles. Then the brass mesh is taped for stability. The conformance of the brass mesh is shown in Fig 2. The patient is treated with the brash mesh until the physician discontinues the brass mesh from the field using skin toxicity (moderate erythema) as a surrogate for an appropriate clinical dose threshold.
In vivo dosimetry In vivo measurements are taken under the brass mesh using the thermoluminescent dosimeter (TLD) or metaloxide-semiconductor field-effect transistor (MOSFET) system. 14 Our MOSFET devices are manufactured by “Best Medical Canada,” in Ottawa, Canada, number TN 502 RDM. We use TLD 100 chips and a Harshaw 3500 reader (supplied by Thermo Scientific, Barrington, IL). Both the TLD and MOSFET systems were calibrated according to the respective manufacturer's recommended procedures. The TLD system is calibrated for absolute dose in a step-wise process. First, a set of 10 calibration chips are set aside. These chips are irradiated under standard calibration conditions in a 6 MV linac beam to determine their individual response, and then the response of the reader to a known amount of dose. Then, the chips that will be used for routine “field” work are calibrated under standard conditions to determine their individual responses. The calibration factors for 6-25 MV photons and 5-19 MeV electron beams range from 0.992-1.0135 with 3.3% variation. 15 Using a 6 MV beam, we used an ion chamber to confirm the output of the machine, which is about 1 cGy/ MU at Dmax = 1.5 cm. We then deliver 100 MU at least 3 times to take an average of the MOSFET readings in order to obtain the calibration factor. The devices are placed on the chest wall by the medical physicist and measurements are taken at 2-5 sites, as seen in Fig 3.
Figure 3
In vivo chest wall standard positions.
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Brass mesh as an alternative bolus in PMRT
Skin toxicity
Table 2 Patient demographic, disease, and treatment summary
Charts were reviewed for overall level of acute skin toxicity following chest wall irradiation. Toxicity was scored using the NCIS during PMRT. Some patients received a boost and final toxicity scores were recorded for a total radiation dose greater than 6000 cGy. In this scoring system, toxicity is graded from no skin change (NCIS = 0) to severe (NCIS = 4). 16 Generally, a score of 0 suggests no skin toxicity: 1= faint to moderate erythema; 2 = moderate to brisk erythema, patchy moist desquamation, that is mostly confined to skin folds and creases, moderate edema; 3 = moist desquamation in areas other than skin folds and creases; 4 = skin necrosis or ulceration of fullthickness dermis and spontaneous bleeding. 16
Characteristic
Results Patient characteristics Forty-eight patients were identified to have received PMRT using brass mesh at UCD between January 2008 and May 2011 (Table 2). Ages ranged from 28-83 years with an average of 58.9. The majority of patients were white and non-Hispanic (n = 35, 74%); however, 5 (10%) patients were African American, 5 (10%) were Asian, and 3 (6%) were Hispanic. Body mass indexes (BMI) ranged from 19.3-56.2, with a median of 27.9 and an average of 29.2. Of the 48 patients, 20 (42%) had BMIs greater than 30.
Disease characteristics All 48 patients' breast cancers were staged at greater than or equal to stage II. Twenty-five (52%) patients had stage II disease, 21 (44%) had stage III disease, and 1 (2%) had stage IV disease. For 1 patient, staging was unknown. Disease characteristics are shown in Table 2.
Treatment characteristics There were 22 right-sided and 26 left-sided PMRT treated. Forty (83%) patients were prescribed chemotherapy prior to PMRT and 7 (15%) were not. Total cumulative radiation dose ranged from 4400 cGy-6600 cGy. Most patients (n = 39, 81%) underwent radiation therapy for 25 fractions, 200 cGy per fraction for a cumulative dose of 5000 cGy. The remainder (n = 9, 19%) received 28 fractions; 180 cGy per fraction for a dose of 5040 cGy. Additionally, 15 (31%) patients received a boost that increased their cumulative dose by 1000 cGy and 2 (4%) received a boost that increased their dose by 1200 cGy. All patients were treated with brass mesh daily until it was discontinued at the discretion of the physician. The dose at which the
Demographics No. of patients Age, y 5-mm mean Median Ethnicity White, non-Hispanic African American Asian Hispanic Body mass index (BMI) Mean Median Obese (BMI N 30) Disease Anatomic stage II IIA IIB IIIA IIIB IIIC IV Unknown Chemotherapy No Yes Unknown Treatment Mastectomy Right Left Fractionation dose, cGy 180 200
No.
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%
48 58.48 56 35 5 5 3 29.22 27.90 20
42
2 9 14 8 6 7 1 1
4 19 29 17 12 14 2 2
7 40 1
15 83 2
22 26
46 54
9 39
19 81
brass mesh was discontinued was recorded for 18 of the 48 patients. The brass mesh was discontinued at 3000 cGy for 1 patient, 3800 cGy for 1 patient, 4000 cGy for 2 patients, 4200 cGy for 7 patients, 4400 cGy for 3 patients, 4600 cGy for 3 patients, 4800 cGy for 1 patient, and the dose at which the mesh was discontinued was not recorded for 30 patients. The average dose that the brass mesh was discontinued was 4222 cGy, but ranged between 3000 cGy and 4800 cGy, with a median dose of 4200 cGy.
Skin toxicity Skin toxicity data are summarized in Fig 4. All patients started PMRT without skin toxicity. Furthermore, in cumulative doses below 1000 cGy, all patients showed a skin toxicity score of 0. In dose ranges of 1000 cGy-1999
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Figure 4
Skin toxicity data. Abbreviation: NCI, National Cancer Institute.
cGy, 35 patients showed no skin toxicity (NCIS = 0) while 13 patients showed mild erythema (NCIS = 1). At cumulative doses of 2000 cGy to 2999 cGy, 16 patients had scores of 0 and the majority (n = 32, 67%) of patients showed mild erythema (NCIS = 1). From 3000 cGy to 3999 cGy, 4 patients showed no skin reaction while 41 (85%) showed mild erythema and 3 patients showed moderate erythema (NCIS = 2). Of the 48 patients who received PMRT using brass mesh, 3 (6%) patients showed no skin toxicity at the end of treatment (NCIS = 0), 19 (40%) showed faint to moderate erythema (NCIS = 1),
23 (48%) showed moderate to brisk erythema (NCIS = 2), and 3 showed moist desquamation (NCIS = 3). The moderate erythema seen at 4000 cGy is shown in Fig 5. Two of the 48 patients did not complete treatment due to skin toxicity and 1 patient required a 1-week break in treatment due to her toxicity, but completed treatment. Using a linear mixed effects model, we looked at the relationship between toxicity score and treatment time. In this model we assumed a population average contribution from the patient's treatment toward expected toxicity level, as well as allowed for variation at the subject level. We found that treatment has a highly significant effect on toxicity. In addition, we measured the differences between toxicity scores during the 5 evaluation visits during the treatment and found that there is a sharp increase in the toxicity scores and a nonlinear increase in skin reaction at the end of the treatment. Given our initial model having a random variance of 0.412, we further investigated the variables of age and BMI to account for our observed variation. Using a linear mixed effects model fit, age and BMI approached statistical significance for skin toxicity with P values of .1109 and .1517, respectively. Age indicated a negative relationship with toxicity suggesting that older patients display less skin toxicity than younger patients. However, our patient population is heavily weighted toward individuals 50 years or older. Patients with BMI greater than 25 showed a higher skin toxicity score. We found no significance between skin toxicity and the type or use of chemotherapy.
In vivo dosimetry
Figure 5
Skin erythema at 4000 cGy.
In vivo dose measurements are shown in Table 3. Sixteen of the 48 total patients (33%) had surface dose measurements recorded by either TLD alone (n = 12) or
Practical Radiation Oncology: April-June 2013 Table 3
Test
Location
Average dose (Gy)/ location
1
TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD MOSFET TLD TLD MOSFET MOSFET TLD TLD TLD TLD TLD TLD TLD
1 2 1 2 3 4 1 2 1 2 3 4 5 1 2 3 4 1 2 3 4 5 1 2 3 4 5 1 2 1 2 3 4 5 1 2 3 4 5 1 2 1 2 3 4 5 1 2 1 2 1 2 3 4 5
2.11 2.23 1.77 1.95 1.99 2.12 2.00 1.92 1.97 1.75 1.84 1.30 1.83 2.26 2.14 1.45 1.60 1.73 1.86 1.88 1.50 1.86 1.84 2.02 1.83 1.95 1.99 1.92 2.07 2.23 2.29 2.08 1.96 2.09 2.13 2.23 2.08 2.31 1.82 2.06 2.13 2.70 2.80 2.58 1.95 2.12 1.67 1.59 1.52 1.74 1.95 2.14 1.99 2.16 2.01
3 4
5
6
7
8 9
10
11 12
13
14
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Thermoluminescent dosimeter (TLD) measurements
Patient no.
2
Brass mesh as an alternative bolus in PMRT
SD a
0.064 0.014 0.021 0.021 0.042 a
0.085 0.212 0.007 0.127 0.092 0.085 0.085 0.085 0.085 0.007 0.049 0.021 0.007 0.064 0.007 0.042
Average surface dose (Gy)
Prescribed dose (Gy)
% of prescribed dose
2.17
2
108
1.96
2
98
1.96
2
98
1.74
2
87
1.86
2
93
1.76
2
88
1.92
2
96
1.99
2
100
2.13
2
106
2.11
2
106
2.09
2
105
2.43
2
122
1.63
2
81
1.63
2
81
2.05
2
102
a
0.035 0.064 0.042 0.085 0.205 0.014 0.431 0.375 0.035 0.064 0.028 a
0.084 0.035 0.021 0.035 0.021 0.091 0.064 a
0.028 a
0.014 0.007 0.049 0.127 0.049 0.021 0.028 0.028 0.028
(continued on next page)
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Table 3 (continued) Patient no.
Test
Location
Average dose (Gy)/ location
SD
Average surface dose (Gy)
Prescribed dose (Gy)
% of prescribed dose
15
MOSFET MOSFET TLD TLD TLD TLD
1 2 1 2 1 2
1.89 2.11 2.12 2.26 1.89 1.935
0.301 0.020
2.00
2
100
2.19
2
110
1.91
2
96
16
a
0.401 0.042 0.035
MOSFET, metal-oxide-semiconductor field-effect transistor; SD, standard deviation. a Single data point.
both TLD and MOSFET (n = 4). Seven patients had measurements taken in 2 areas, 2 patients had measurements taken in 4 areas, and 7 patients had measurements taken in 5 areas. Average surface doses ranged from 81%122% of the prescribed dose, with an average of 99% of the prescribed dose being delivered and a standard deviation of 10%.
Discussion PMRT decreases local recurrence and increases survival for patients with locally advanced breast cancer. 3-5,10 The American Society of Clinical Oncology has guidelines on the appropriateness of PMRT, but does not provide details on whether a bolus should be employed. In fact, in a consensus guidelines statement from the American College of Radiology, the “use of bolus is usually considered to be substantial; hence, the use of bolus to increase the skin dose is common. Whether it is necessary to apply bolus every day or less frequently is uncertain.” 17 Furthermore, there is high variability on the use and specifications of techniques to increase superficial dose. In a publication by Vu et al, 18 the authors describe the variability in practice patterns after reviewing survey data compiled from 1035 radiation oncologists for the use of a bolus in the PMRT. Only 68% of responders always used a bolus, with 6% never using one, and 26% used a bolus according to various indications. 82% of Americans always used a bolus, with 49% of Europeans using a bolus depending on the clinical scenario. Further, there is profound variability in all aspects of using of a bolus in chest wall PMRT including its application, material, thickness and frequency of its use. 18 The use of fine brass mesh in chest wall PMRT as an alternative to TEB is relatively uncommon. The purpose of this study was to characterize the skin changes associated with using 2-mm fine brass mesh over the chest wall during PMRT. As expected, skin toxicity scores increased with successive treatment fractions. Mean toxicity response at the end of treatment was less than 2 (moderate
erythema). Anatomic stage, body habitus, number of fields treated, and the use of adjuvant chemotherapy did not appear to have a statistically significant effect on skin reaction. However, those patients with a BMI of greater than 25 had increased skin toxicity scores. Our results from the in vivo dosimetry validated our surface target dose. The average dose delivered to the patient surface with the brass mesh was 4222 cGy. The main question regarding PMRT dose is, What is the optimal dose needed for local control of the chest wall? In our study, the brass mesh was discontinued at a median value of 4200 cGy once a brisk skin reaction was observed. However, depending on patient characteristics or contributing factors such as prior sun exposure or ethnicity, skin reactions may differ between patients. Therefore, skin reaction may not be the ideal surrogate for adequate dose achieved for optimal control. As described in the literature of techniques used in PMRT, some studies use a bolus every other day. 13 Using this option as an example, this would be equivalent to ð200 cGy = fx × 12 fxÞ + ð200 cGy = fx × 0:8ðsurfacedoseÞ × 13 fractionsÞ = 4480 cGy: A lingering question is to determine a surface dose threshold to discontinue the brass mesh or bolus regardless of skin toxicity.
Limitations Potential limitations of this study include its size. Because this study only included patients treated at a single institution, the population size was relatively small and lacked significant diversity. Most patients were Caucasian women aged 50 or older, which made it difficult to draw statistically significant associations between patient characteristics and treatment outcomes. On average, each patient was only scored 5 times over the course of their treatment. Because of this, it was difficult to assess exactly at which point most patients began developing more severe skin reactions. This study,
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however, provided approximate ranges of cumulative radiation dose that correspond to average skin toxicity scores, which might be more clinically useful. Also, because scores were recorded during treatment, the results are limited to acute skin toxicity and not the long-term skin effects of chest wall radiation therapy. Although the use of the NCI skin toxicity scoring system attempts to standardize skin toxicity quantification, a small amount of subjectivity is involved in assigning scores. As a result, assigned scores may vary between treating physicians. This difference, however, is unlikely to have a dramatic impact on the average results seen in this study. Lastly, although the skin serves as a surrogate for adequate dose response, this can be more related to patient sensitivity to radiation as opposed to being a marker for adequate dose delivered. Consequently, in vivo dosimetry was used in combination with skin reaction in order to validate the dose of radiation delivered to the surface.
Brass mesh as an alternative bolus in PMRT
2.
3.
4.
5.
6. 7.
8.
Conclusions Our study is the only contribution to the literature investigating the clinical use of brass mesh as an alternative to TEB for patients treated with postmastectomy chest wall radiation therapy. Like a traditional TEB, it decreases the radiation buildup depth and thereby increases radiation dose delivered to the skin. As seen in this study, when brass mesh is used in chest wall PMRT, the majority of patients (88%, n = 42) will achieve faint to moderate erythema (NCIS = 1) or moderate to brisk erythema (NCIS = 2) at cumulative radiation doses of approximately 5 Gy. Also, as shown by in vivo dosimetry readings, surface doses were found to be within 99% ± 10% of the prescribed dose on average using brass mesh as TEB.
9. 10.
11.
12.
13.
14. 15.
Acknowledgment
16.
The authors thank Scott Dube, MS, medical physicist, for his expertise. 17.
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18.
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positive nodes, as recommended in international consensus reports? A subgroup analysis of the DBCG 82 b&c randomized trials. Radiother Oncol. 2007;82:247-253. Ragaz J, Olivotto IA, Spinelli JJ, et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst. 2005;97:116-126. Ragaz J, Jackson SM, Le N, et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med. 1997;337:956-962. Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med. 1997;337:949-955. Overgaard M, Jensen MB, Overgaard J, et al. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet. 1999;353:1641-1648. Strom EA, McNeese MD. Postmastectomy irradiation rationale for treatment field selection. Semin Radiat Oncol. 1999;9:247-253. Recht A, Gray R, Davidson NE, et al. Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: experience of the Eastern Cooperative Oncology Group. J Clin Oncol. 1999;17:1689-1700. Taghian A, Jeong JH, Mamounas E, et al. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with our without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004;22: 4247-4254. Recht A, Houlihan MJ. Axillary lymph nodes and breast cancer. A review. Cancer. 1995;76:1491-1512. Fernando SA, Edge SB. Evidence and controversies in the use of post-mastectomy radiation. J Natl Compr Canc Netw. 2007;5: 331-338. Hsu SH, Roberson PL, Chen Y, Marsh RB, Pierce LJ, Moran JM. Assessment of skin dose for breast chest wall radiotherapy as a function of bolus material. Phys Med Biol. 2008;53:2593-2606. Andic F, Ors Y, Davutoglu R, Baz Cifci S, Ispir EB, Erturk ME. Evaluation of skin dose associated with different frequencies of bolus applications in post-mastectomy three-dimensional conformal radiotherapy. J Exp Clin Cancer Res. 2009;28:41. Thoms Jr WW, McNeese MD, Fletcher GH, Buzdar AU, Singletary SE, Oswald MJ. Multimodal treatment for inflammatory breast cancer. Int J Radiat Oncol Biol Phys. 1989;17:739-745. Kwan IS, Rosenfeld AB, Qi Z, et al. Skin dosimetry with new MOSFET detectors. Radiat Meas. 2008;43:929-932. Ramani R, Russell S, O'Brien P. Clinical dosimetry using MOSFETs. Int J Radiat Oncol Biol Phys. 1997;37:959-964. Balter S, Hopewell JW, Miller DL, Wagner LK, Zelefsky MJ. Fluoroscopically guided interventional procedures: a review of radiation effects on patients' skin and hair. Radiology. 2010;254: 326-341. Taylor ME, Haffty BG, Rabinovitch R, et al. ACR appropriateness criteria on postmastectomy radiotherapy expert panel on radiation oncology-breast. Int J Radiat Oncol Biol Phys. 2009;73(4):997-1002. Vu TTT, Pignol JP, Rakovitch E, Spayne J, Paszat L. Variability in radiation oncologists' opinion on the indication of a bolus in postmastectomy radiotherapy: an international survey. J Clin Oncol. 2007;19:115-119.
www.practicalradonc.org
Original Report
Skin dose effects of postmastectomy chest wall radiation therapy using brass mesh as an alternative to tissue equivalent bolus Erin Healy MA a , Shawnee Anderson BA b , Jing Cui DSc c , Laurel Beckett PhD d , Allen M. Chen MD c , Julian Perks PhD c , Robin Stern PhD c , Jyoti Mayadev MD c,⁎ a
University of California, Davis, Sacramento, California Department of Mathematics, California State University, Sacramento, California c Department of Radiation Oncology, University of California, Davis, Sacramento, California d Department of Biostatistics, University of California, Davis, Sacramento, California b
Received 29 February 2012; revised 25 May 2012; accepted 29 May 2012
Abstract Purpose: The use of brass mesh as a bolus is relatively uncommon in postmastectomy chest wall radiation therapy (PMRT). This study aimed to characterize the skin dose effects of using 2-mm fine brass mesh as an alternative to the traditional tissue-equivalent bolus during chest wall PMRT. Methods and Materials: Data were collected from patients who received PMRT using brass mesh at the University of California Davis Department of Radiation Oncology between January 2008 and June 2011. Several patient characteristics including age, body habitus, and ethnicity were analyzed along with several disease and treatment characteristics to determine whether or not they had an impact on the skin reaction observed during radiation treatment. Additionally, in vivo surface dose measurements were obtained for 16 of the 48 patients (33%). Results: Forty-eight female patients aged 28-83 received PMRT using brass mesh. As expected, the severity of skin toxicity increased with subsequent doses of radiation with all patients beginning treatment with no skin reaction (National Cancer Institute scores [NCIS] = 0) and the majority of patients completing treatment with either faint to moderate erythema (n = 19, 40%, NCIS = 1) or moderate to brisk erythema (n = 23, 48%, NCIS = 2). In vivo dosimetry analysis revealed surface doses between 81% and 122% of the prescribed dose, with an average of 99% of the prescribed radiation dose and standard deviation of 10% being delivered. Conclusions: For postmastectomy chest wall radiation therapy, brass mesh is an effective alternative to tissue-equivalent bolus. The brass mesh achieved moderate erythema in the majority of patients at the end of treatment and the surface dose was validated using in vivo dosimetry. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.
Conflicts of interest: None. Sources of support: Medical student fellowship from the University of California, Davis, Sacramento, California. ⁎ Corresponding author. University of California Davis Medical Center, Radiation Oncology, 4501 X St, Sacramento, CA 95817. E-mail address: [email protected] (J. Mayadev).
Introduction Postmastectomy radiation therapy (PMRT) has been proven to increase the locoregional and overall survival of patients with locally advanced breast cancer. 1-5 The area at
1879-8500/$ – see front matter. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. http://dx.doi.org/10.1016/j.prro.2012.05.009
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highest risk for local regional recurrence is the chest wall. In fact, the target volume at risk for postmastectomy patients includes the entire soft tissue of the chest wall including residual breast tissue, surrounding skin, connective tissue, and the regional lymphatics. 3,6-9 Long-term locoregional failure rates may be as high as 40%. 10 The chest wall is a challenge to treat with radiation therapy due to its irregular surface contours, large curvature and near-surface target tissue volume. 11 Consequently the goals of postmastectomy radiation are to deliver adequate radiation to the chest wall while limiting toxicity to tissues outside of the target volume. 11 Furthermore, the risk of a skin recurrence is usually considered to be substantial. The dose at the skin for megavoltage photon treatments is influenced by the electron contamination from the flattening filter, source to skin distance, beam modifiers, and beam characteristics such as angle incidence, energy, and field size. For 6-MV photons, the depth of maximum dose (Dmax) is 1.5 cm, with the surface dose substantially lower. For opposed tangential fields, this “skin sparing” translates into a skin dose of about 80% of prescription. Often, tissue-equivalent bolus (TEB) is used during the course of PMRT to increase surface dose to the target tissue volume. 11,12 TEB contributes to the dose build-up and yields adequate dose contribution to the skin and shallow tissues. Studies have shown that surface dose is increased with the use of TEB material over the chest wall. 11 This material, however, due to its thickness and inflexibility, adds another layer of complexity to the already challenging task of treating PMRT. Due to its rigidity, air gaps are often introduced between TEB and the skin that can potentially cause a skin sparing effect in the radiation dose that is delivered to the chest wall. In addition, if TEB is to be used and subsequently discontinued, 2 treatment plans must be generated to accurately depict the patient's dose distribution during the radiation treatment course.
In 2008, the Radiation Oncology Department at the University of California, Davis (UCD) began using a fine brass mesh (Fig 1; Whiting and Davis, North Attleboro, MA) when delivering PMRT as an alternative to TEB. The enhanced dose to the skin at the skin-mesh interface is due primarily to secondary charged particles produced in the mesh. The mesh conforms to the irregular contours of the chest wall with fewer gaps better than TEB material. Furthermore, during the commission of the clinical use of brass mesh, in-house testing by our physics team showed that the mesh did not affect the dose below Dmax and that monitor units (MUs) did not change substantially with its use. As a result, the use of brass mesh reduces the complexity of accounting for a bolus in simulation and treatment planning. Surface skin reaction is important in the PMRT setting as it has been shown that local control is improved when brisk erythema or moist desquamation is achieved. 13 During treatment, the surface dose can be assessed visually by observing the reaction of the overlying skin. In addition, we have investigated surface dose measurements for patients treated with brass mesh. Although the effects of using TEB are well documented, the effects of using brass mesh to decrease the buildup depth are not as well studied. 11,12 This investigation aimed to characterize the skin changes associated with using brass mesh during PMRT at UCD from January 2008 to June 2011.
Methods and materials Patient characteristics After approval by the institutional review board at University of California Davis Medical Center, we identified patients with breast cancer who were treated with PMRT using brass mesh as a TEB between January 2008 and June 2011 at UCD. Inclusion criteria were patients with a known diagnosis of breast cancer who were treated with mastectomy followed by chest wall irradiation at UCD. These patients were then cross-referenced with the radiation oncology database to determine if brass mesh was used during chest wall irradiation and 48 patients were identified. Data for demographics, stage at diagnosis and pathology, radiation dose, fractionation, beam energy, area, surgical technique, reconstruction, chemotherapy, and side effects were extracted.
Treatment
Figure 1
Brass mesh.
All patients were treated with a mastectomy and either a sentinel lymph node biopsy or an axillary dissection. Adjuvant chemotherapy and radiation therapy were delivered based on the National Comprehensive Cancer Network practice guidelines. In those patients requiring
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chemotherapy, this was delivered prior to radiation therapy, and after the mastectomy. The type of chemotherapy delivered is seen in Table 1. Overall, 28 (58%) patients
Table 1
Brass mesh as an alternative bolus in PMRT
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received chemotherapy with doxorubicin (Adriamycin)containing regimens. Eleven (23%) patients received concurrent and adjuvant treatment with trastuzumab.
Patient characteristics
Age (y)
Hormone receptor status
Chemotherapy
Fields
Total cumulative dose (cGy)
28 33 39 40 42 42 43 43 45 46 49 50 50 51 52 52 53 53 53 53 54 54 56 56 56 59 60 60 61 61 61 67 67 69 69 69 70 70 71 72 73 74 77 77 80 81 83 83
ER +/PR+ HER2+ HER2+ ER-/PR-/HER2ER +/PR+ ER +/PR+ Unknown ER +/PR+ ER +/PR+ ER +/PR+ ER + ER +/PR+ HER2+ HER2+ ER-/PR-/HER2ER-/PR-/HER2ER +/PR+/HER2 + Unknown Unknown ER-/PR-/HER2ER +/PR+/HER2 + ER-/PR-/HER2ER +/PR+ ER +/PR+ ER + ER +/PR+ ER +/PR+ HER2+ ER +/PR+ ER-/PR-/HER2HER2+ ER +/PR+ ER +/PR+ HER2+ HER2+ ER-/PR-/HER2ER +/PR+ ER-/PR-/HER2ER-/PR-/HER2ER +/PR+ ER +/PR+ ER +/PR+/HER2 + ER +/PR+ HER2+ Unknown ER +/PR+ ER +/PR+ ER +/PR+
DXN/CYP + PTL DTX/CRB + TRB 5-FU/DXN/CYP + PTL/TRB DXN/CYP + PTL DXN/CYP + DTX + TMX DXN/CYP + PTL/BVZ Unknown DXN/CYP + PTL, DTX ddDXN/CYP + ddPTL DXN/PTL + BVZ DXN + PTL DXN + PTL DXN + PTL/TRB, CYP DXN/CYP + PTL/TRB DXN/CYP + PTL DXN/CYP + DTX DXN/CYP + PTL/TRB DXN/CYP + PLT ddDXN + PTL ddDXN/CYP + PTL DXN/CYP + PTL/TRB None DTX/CYP ddDXN/PTL CMF + DXN, DTX + CYP DXN/CYP + PTL/BVZ None DXN + PTL DXN/CYP + PTL DXN/CYP/PLT DXN/CYP + PTL/TRB, -PTL+PTL DTX or DTX/CYP DXN/PTL DTX + TRB, PTL/TRB DTX/CRB + TRB None None DTX/CYP TMX None DTX/CYP DTX/CRB/TRB + TRB ddDXN + PTL PTL/TRB, CPB/TRB None DXN/CYP + DTX TMX None
3 3 3 4 5 6 3 7 7 5 4 4 4 5 5 4 5 3 4 3 5 3 3 2 3 3 2 3 2 4 4 3 3 5 5 3 5 5 5 2 4 3 3 6 3 5 3 5
6040 5000 5000 5040 5000 5000 6000 5000 5000 5000 5040 5000 5000 5040 5000 5000 5000 5000 5000 5000 5000 5040 6000 6200 5000 5000 5000 5000 5000 4600 6000 5000 5000 6000 5040 5600 4400 5000 5040 6000 5040 6000 5000 6200 5000 6000 6000 6000
5-FU, fluorouracil; dd, double dose; BVZ, bevacizumab/Avastin; CPB, capecitabine/Xeloda; CRB, carboplatin; CYP, cyclophosphamide/Cytoxan; DTX, docetaxel/Taxotere; DXN, doxorubicin/Adriamycin; ER, estrogen receptor; HER2, human epidermal growth receptor-2; PR, progesterone receptor; PTL, paclitaxel/Taxol/Abraxane; TMX, tamoxifen; TRB, trastuzumab/Herceptin.
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Radiation treatment parameters Patients were treated with PMRT using opposed tangential 6-MV photons. During the treatment period, all fields were treated daily for 5 of 7 days per week. Additional fields or a boost were at the discretion of the treating physician. Forty-three (90%) patients received a supraclavicular field, and 17 (35%) patients received a chest wall boost. The boost was delivered without bolus using en face electron fields with electron dosimetry. Treatment planning was done without accounting for the mesh bolus because the planning system cannot model the bolus and because tests showed that doses below Dmax were unaffected by it. During the commission of the clinical use of the brass mesh, we performed relative dose measurements on water-equivalent phantom using 6× and 15× photon beams, with and without the mesh. For both energies, the dose at Dmax was within 0.4%, with and without the mesh. Further measurements showed that the dose at depths down to 10 cm varied by b 1%, therefore the same MUs can be used with the mesh as calculated without it.
Brass mesh parameters Brass mesh was overlaid on the patient's chest wall over 1 layer of pillowcase. Our group has conducted measurements using 1 layer of pillowcase versus no pillowcase and found that for electron fields, the skin dose does not change by adding a pillowcase underneath the bolus except for 6e, for which the skin dose increases by 1%. For photon fields, the skin dose increases by 1%-2% which is still minimal. Thus, a pillowcase can be used as a separation between the patient's skin and bolus material without the need to adjust
Figure 2
Conformance of the brass mesh.
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the planned MU. The therapists visualize the brass mesh on the treatment field and smooth out the wrinkles. Then the brass mesh is taped for stability. The conformance of the brass mesh is shown in Fig 2. The patient is treated with the brash mesh until the physician discontinues the brass mesh from the field using skin toxicity (moderate erythema) as a surrogate for an appropriate clinical dose threshold.
In vivo dosimetry In vivo measurements are taken under the brass mesh using the thermoluminescent dosimeter (TLD) or metaloxide-semiconductor field-effect transistor (MOSFET) system. 14 Our MOSFET devices are manufactured by “Best Medical Canada,” in Ottawa, Canada, number TN 502 RDM. We use TLD 100 chips and a Harshaw 3500 reader (supplied by Thermo Scientific, Barrington, IL). Both the TLD and MOSFET systems were calibrated according to the respective manufacturer's recommended procedures. The TLD system is calibrated for absolute dose in a step-wise process. First, a set of 10 calibration chips are set aside. These chips are irradiated under standard calibration conditions in a 6 MV linac beam to determine their individual response, and then the response of the reader to a known amount of dose. Then, the chips that will be used for routine “field” work are calibrated under standard conditions to determine their individual responses. The calibration factors for 6-25 MV photons and 5-19 MeV electron beams range from 0.992-1.0135 with 3.3% variation. 15 Using a 6 MV beam, we used an ion chamber to confirm the output of the machine, which is about 1 cGy/ MU at Dmax = 1.5 cm. We then deliver 100 MU at least 3 times to take an average of the MOSFET readings in order to obtain the calibration factor. The devices are placed on the chest wall by the medical physicist and measurements are taken at 2-5 sites, as seen in Fig 3.
Figure 3
In vivo chest wall standard positions.
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Brass mesh as an alternative bolus in PMRT
Skin toxicity
Table 2 Patient demographic, disease, and treatment summary
Charts were reviewed for overall level of acute skin toxicity following chest wall irradiation. Toxicity was scored using the NCIS during PMRT. Some patients received a boost and final toxicity scores were recorded for a total radiation dose greater than 6000 cGy. In this scoring system, toxicity is graded from no skin change (NCIS = 0) to severe (NCIS = 4). 16 Generally, a score of 0 suggests no skin toxicity: 1= faint to moderate erythema; 2 = moderate to brisk erythema, patchy moist desquamation, that is mostly confined to skin folds and creases, moderate edema; 3 = moist desquamation in areas other than skin folds and creases; 4 = skin necrosis or ulceration of fullthickness dermis and spontaneous bleeding. 16
Characteristic
Results Patient characteristics Forty-eight patients were identified to have received PMRT using brass mesh at UCD between January 2008 and May 2011 (Table 2). Ages ranged from 28-83 years with an average of 58.9. The majority of patients were white and non-Hispanic (n = 35, 74%); however, 5 (10%) patients were African American, 5 (10%) were Asian, and 3 (6%) were Hispanic. Body mass indexes (BMI) ranged from 19.3-56.2, with a median of 27.9 and an average of 29.2. Of the 48 patients, 20 (42%) had BMIs greater than 30.
Disease characteristics All 48 patients' breast cancers were staged at greater than or equal to stage II. Twenty-five (52%) patients had stage II disease, 21 (44%) had stage III disease, and 1 (2%) had stage IV disease. For 1 patient, staging was unknown. Disease characteristics are shown in Table 2.
Treatment characteristics There were 22 right-sided and 26 left-sided PMRT treated. Forty (83%) patients were prescribed chemotherapy prior to PMRT and 7 (15%) were not. Total cumulative radiation dose ranged from 4400 cGy-6600 cGy. Most patients (n = 39, 81%) underwent radiation therapy for 25 fractions, 200 cGy per fraction for a cumulative dose of 5000 cGy. The remainder (n = 9, 19%) received 28 fractions; 180 cGy per fraction for a dose of 5040 cGy. Additionally, 15 (31%) patients received a boost that increased their cumulative dose by 1000 cGy and 2 (4%) received a boost that increased their dose by 1200 cGy. All patients were treated with brass mesh daily until it was discontinued at the discretion of the physician. The dose at which the
Demographics No. of patients Age, y 5-mm mean Median Ethnicity White, non-Hispanic African American Asian Hispanic Body mass index (BMI) Mean Median Obese (BMI N 30) Disease Anatomic stage II IIA IIB IIIA IIIB IIIC IV Unknown Chemotherapy No Yes Unknown Treatment Mastectomy Right Left Fractionation dose, cGy 180 200
No.
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%
48 58.48 56 35 5 5 3 29.22 27.90 20
42
2 9 14 8 6 7 1 1
4 19 29 17 12 14 2 2
7 40 1
15 83 2
22 26
46 54
9 39
19 81
brass mesh was discontinued was recorded for 18 of the 48 patients. The brass mesh was discontinued at 3000 cGy for 1 patient, 3800 cGy for 1 patient, 4000 cGy for 2 patients, 4200 cGy for 7 patients, 4400 cGy for 3 patients, 4600 cGy for 3 patients, 4800 cGy for 1 patient, and the dose at which the mesh was discontinued was not recorded for 30 patients. The average dose that the brass mesh was discontinued was 4222 cGy, but ranged between 3000 cGy and 4800 cGy, with a median dose of 4200 cGy.
Skin toxicity Skin toxicity data are summarized in Fig 4. All patients started PMRT without skin toxicity. Furthermore, in cumulative doses below 1000 cGy, all patients showed a skin toxicity score of 0. In dose ranges of 1000 cGy-1999
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Figure 4
Skin toxicity data. Abbreviation: NCI, National Cancer Institute.
cGy, 35 patients showed no skin toxicity (NCIS = 0) while 13 patients showed mild erythema (NCIS = 1). At cumulative doses of 2000 cGy to 2999 cGy, 16 patients had scores of 0 and the majority (n = 32, 67%) of patients showed mild erythema (NCIS = 1). From 3000 cGy to 3999 cGy, 4 patients showed no skin reaction while 41 (85%) showed mild erythema and 3 patients showed moderate erythema (NCIS = 2). Of the 48 patients who received PMRT using brass mesh, 3 (6%) patients showed no skin toxicity at the end of treatment (NCIS = 0), 19 (40%) showed faint to moderate erythema (NCIS = 1),
23 (48%) showed moderate to brisk erythema (NCIS = 2), and 3 showed moist desquamation (NCIS = 3). The moderate erythema seen at 4000 cGy is shown in Fig 5. Two of the 48 patients did not complete treatment due to skin toxicity and 1 patient required a 1-week break in treatment due to her toxicity, but completed treatment. Using a linear mixed effects model, we looked at the relationship between toxicity score and treatment time. In this model we assumed a population average contribution from the patient's treatment toward expected toxicity level, as well as allowed for variation at the subject level. We found that treatment has a highly significant effect on toxicity. In addition, we measured the differences between toxicity scores during the 5 evaluation visits during the treatment and found that there is a sharp increase in the toxicity scores and a nonlinear increase in skin reaction at the end of the treatment. Given our initial model having a random variance of 0.412, we further investigated the variables of age and BMI to account for our observed variation. Using a linear mixed effects model fit, age and BMI approached statistical significance for skin toxicity with P values of .1109 and .1517, respectively. Age indicated a negative relationship with toxicity suggesting that older patients display less skin toxicity than younger patients. However, our patient population is heavily weighted toward individuals 50 years or older. Patients with BMI greater than 25 showed a higher skin toxicity score. We found no significance between skin toxicity and the type or use of chemotherapy.
In vivo dosimetry
Figure 5
Skin erythema at 4000 cGy.
In vivo dose measurements are shown in Table 3. Sixteen of the 48 total patients (33%) had surface dose measurements recorded by either TLD alone (n = 12) or
Practical Radiation Oncology: April-June 2013 Table 3
Test
Location
Average dose (Gy)/ location
1
TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD TLD MOSFET TLD TLD MOSFET MOSFET TLD TLD TLD TLD TLD TLD TLD
1 2 1 2 3 4 1 2 1 2 3 4 5 1 2 3 4 1 2 3 4 5 1 2 3 4 5 1 2 1 2 3 4 5 1 2 3 4 5 1 2 1 2 3 4 5 1 2 1 2 1 2 3 4 5
2.11 2.23 1.77 1.95 1.99 2.12 2.00 1.92 1.97 1.75 1.84 1.30 1.83 2.26 2.14 1.45 1.60 1.73 1.86 1.88 1.50 1.86 1.84 2.02 1.83 1.95 1.99 1.92 2.07 2.23 2.29 2.08 1.96 2.09 2.13 2.23 2.08 2.31 1.82 2.06 2.13 2.70 2.80 2.58 1.95 2.12 1.67 1.59 1.52 1.74 1.95 2.14 1.99 2.16 2.01
3 4
5
6
7
8 9
10
11 12
13
14
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Thermoluminescent dosimeter (TLD) measurements
Patient no.
2
Brass mesh as an alternative bolus in PMRT
SD a
0.064 0.014 0.021 0.021 0.042 a
0.085 0.212 0.007 0.127 0.092 0.085 0.085 0.085 0.085 0.007 0.049 0.021 0.007 0.064 0.007 0.042
Average surface dose (Gy)
Prescribed dose (Gy)
% of prescribed dose
2.17
2
108
1.96
2
98
1.96
2
98
1.74
2
87
1.86
2
93
1.76
2
88
1.92
2
96
1.99
2
100
2.13
2
106
2.11
2
106
2.09
2
105
2.43
2
122
1.63
2
81
1.63
2
81
2.05
2
102
a
0.035 0.064 0.042 0.085 0.205 0.014 0.431 0.375 0.035 0.064 0.028 a
0.084 0.035 0.021 0.035 0.021 0.091 0.064 a
0.028 a
0.014 0.007 0.049 0.127 0.049 0.021 0.028 0.028 0.028
(continued on next page)
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Table 3 (continued) Patient no.
Test
Location
Average dose (Gy)/ location
SD
Average surface dose (Gy)
Prescribed dose (Gy)
% of prescribed dose
15
MOSFET MOSFET TLD TLD TLD TLD
1 2 1 2 1 2
1.89 2.11 2.12 2.26 1.89 1.935
0.301 0.020
2.00
2
100
2.19
2
110
1.91
2
96
16
a
0.401 0.042 0.035
MOSFET, metal-oxide-semiconductor field-effect transistor; SD, standard deviation. a Single data point.
both TLD and MOSFET (n = 4). Seven patients had measurements taken in 2 areas, 2 patients had measurements taken in 4 areas, and 7 patients had measurements taken in 5 areas. Average surface doses ranged from 81%122% of the prescribed dose, with an average of 99% of the prescribed dose being delivered and a standard deviation of 10%.
Discussion PMRT decreases local recurrence and increases survival for patients with locally advanced breast cancer. 3-5,10 The American Society of Clinical Oncology has guidelines on the appropriateness of PMRT, but does not provide details on whether a bolus should be employed. In fact, in a consensus guidelines statement from the American College of Radiology, the “use of bolus is usually considered to be substantial; hence, the use of bolus to increase the skin dose is common. Whether it is necessary to apply bolus every day or less frequently is uncertain.” 17 Furthermore, there is high variability on the use and specifications of techniques to increase superficial dose. In a publication by Vu et al, 18 the authors describe the variability in practice patterns after reviewing survey data compiled from 1035 radiation oncologists for the use of a bolus in the PMRT. Only 68% of responders always used a bolus, with 6% never using one, and 26% used a bolus according to various indications. 82% of Americans always used a bolus, with 49% of Europeans using a bolus depending on the clinical scenario. Further, there is profound variability in all aspects of using of a bolus in chest wall PMRT including its application, material, thickness and frequency of its use. 18 The use of fine brass mesh in chest wall PMRT as an alternative to TEB is relatively uncommon. The purpose of this study was to characterize the skin changes associated with using 2-mm fine brass mesh over the chest wall during PMRT. As expected, skin toxicity scores increased with successive treatment fractions. Mean toxicity response at the end of treatment was less than 2 (moderate
erythema). Anatomic stage, body habitus, number of fields treated, and the use of adjuvant chemotherapy did not appear to have a statistically significant effect on skin reaction. However, those patients with a BMI of greater than 25 had increased skin toxicity scores. Our results from the in vivo dosimetry validated our surface target dose. The average dose delivered to the patient surface with the brass mesh was 4222 cGy. The main question regarding PMRT dose is, What is the optimal dose needed for local control of the chest wall? In our study, the brass mesh was discontinued at a median value of 4200 cGy once a brisk skin reaction was observed. However, depending on patient characteristics or contributing factors such as prior sun exposure or ethnicity, skin reactions may differ between patients. Therefore, skin reaction may not be the ideal surrogate for adequate dose achieved for optimal control. As described in the literature of techniques used in PMRT, some studies use a bolus every other day. 13 Using this option as an example, this would be equivalent to ð200 cGy = fx × 12 fxÞ + ð200 cGy = fx × 0:8ðsurfacedoseÞ × 13 fractionsÞ = 4480 cGy: A lingering question is to determine a surface dose threshold to discontinue the brass mesh or bolus regardless of skin toxicity.
Limitations Potential limitations of this study include its size. Because this study only included patients treated at a single institution, the population size was relatively small and lacked significant diversity. Most patients were Caucasian women aged 50 or older, which made it difficult to draw statistically significant associations between patient characteristics and treatment outcomes. On average, each patient was only scored 5 times over the course of their treatment. Because of this, it was difficult to assess exactly at which point most patients began developing more severe skin reactions. This study,
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however, provided approximate ranges of cumulative radiation dose that correspond to average skin toxicity scores, which might be more clinically useful. Also, because scores were recorded during treatment, the results are limited to acute skin toxicity and not the long-term skin effects of chest wall radiation therapy. Although the use of the NCI skin toxicity scoring system attempts to standardize skin toxicity quantification, a small amount of subjectivity is involved in assigning scores. As a result, assigned scores may vary between treating physicians. This difference, however, is unlikely to have a dramatic impact on the average results seen in this study. Lastly, although the skin serves as a surrogate for adequate dose response, this can be more related to patient sensitivity to radiation as opposed to being a marker for adequate dose delivered. Consequently, in vivo dosimetry was used in combination with skin reaction in order to validate the dose of radiation delivered to the surface.
Brass mesh as an alternative bolus in PMRT
2.
3.
4.
5.
6. 7.
8.
Conclusions Our study is the only contribution to the literature investigating the clinical use of brass mesh as an alternative to TEB for patients treated with postmastectomy chest wall radiation therapy. Like a traditional TEB, it decreases the radiation buildup depth and thereby increases radiation dose delivered to the skin. As seen in this study, when brass mesh is used in chest wall PMRT, the majority of patients (88%, n = 42) will achieve faint to moderate erythema (NCIS = 1) or moderate to brisk erythema (NCIS = 2) at cumulative radiation doses of approximately 5 Gy. Also, as shown by in vivo dosimetry readings, surface doses were found to be within 99% ± 10% of the prescribed dose on average using brass mesh as TEB.
9. 10.
11.
12.
13.
14. 15.
Acknowledgment
16.
The authors thank Scott Dube, MS, medical physicist, for his expertise. 17.
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