Electron arc irradiation of the postmastectomy chest wall: clinical results

ADIOTHERAPY EL & ONCOLOGY ELSEVIER

Radiotherapyand Oncology 42 (1997) 17-24

Electron arc irradiation of the postmastectomy chest wall: clinical results’ David K. Gaffney”‘“, ‘Department ‘Department

Janalyn Prowsb, Dennis D. LeavitP, Marlene J. Egger”, John G. Morgan”, J. Robert Stewart”

of Radiation

of Family

Oncology, University of Utah Health Sciences Center, 50 N. Medical Dr., Salt Lake City, Utah 84132, USA bMidwest Radiation Oncology Clinic, Methodist Hospital, Omaha, Nebraska, USA and Preventive Medicine, University of Utah Health Sciences Center, 50 N. Medical Dr., Salt Lake City, Utah 84132, Received

21 March

USA

1996; revised 6 September1996;accepted21 October 1996

Abstract Background and purpose: Since 1980 electron arc irradiation of the postmastectomy chest wall has been the preferred technique for patients with advanced breast cancer at our institution. Here we report the results of this technique in 140 consecutive patients treated from 1980 to 1993. Materials and Methods: Thoracic computerized tomography was used to determine internal mammary lymph node depth and chest wall thickness, and for computerized dosimehy calculations. Total doses of 45-50 Gy in 5 to 5 l/2 weeks were delivered to the chest wall and internal mammary lymph nodes via electron arc and, in most cases, supraclavicular and axillary nodes were treated with a matching photon field. Patients were assessed for acute and late radiation changes, local and distant control of disease, and survival. Patients had a minimum follow-up of 1 year after completion of radiation treatment, and a mean follow up interval of 49 months and a median of 33 months. All patients had advanced disease: T stages 1, 2, 3, and 4 represented 21%, 39%, 21% and 19% of the study population, with a mean number of positive axillary lymph nodes of 6.5 (range, O-29). Analysis was performed according to adjuvant status (no residual disease, n=90), residual disease (positive margin, n= 15, and primary radiation, n=2), or recurrent disease (n=33). Results: Acute radiationreactionsweregenerallymild and selflimiting. A total of 26%of patientsdevelopedmoistdesquamation, and 32% hadbriskerythema.Actuarial 5 year local-regionalcontrol, freedomfrom distantfailure, andcause-specific survival was91%, 64%, and 75% in the adjuvantgroup; 84%, 50%, and 53% in the residualdiseasegroup; and 63%, 34%, and 32% in the recurrentdisease group, respectively.In univariateCox regressions, the numberof positive lymph nodeswas predictivefor local failure in the adjuvant group (P=O.O37).Chronic complicationswere minimal with 11% of patientshaving arm edema,17% hyperpigmentation,and 13% telangectasia formation. Conclusion: Thesedata demonstratethat local-regionalcontrol with electron arc therapy of the postmastectomy chest wall is comparableto photontechniques.Acute radiationreactionsarewell toleratedandmostly of minorextent. A previousreportdemonstrated a significantreduction in the dose-volumerelationshipof the lung using the electron arc comparedwith two photon techniques. Consequently,with careful attentionto treatmentplanninganddosimetry,electronarc therapy of the postmastectomy chestwall is safe andeffective. The radiationdoseto heartandlung is minimizedwithout compromise on local control. 0 1997,ElsevierScienceIreland Ltd. All rights reserved

Keywords:

Breastcancer;Postmastectomy; Chestwall; Electronarc; Rotationaltherapy

1. Introduction

ment, although the impact on overall survival is contentious. Two modern trials suggest a survival benefit for Irradiation of the post-mastectomy chest wall and repost-operative irradiation to the chest wall and regional gional lymphatics in breast cancer patients is an important lymphatics [29,31]. A recent meta-analysis has demoncomponent for local control in multidisciplinary managestrated a trend toward an increase in survival for those patients who underwent post-operative irradiation, along with a trend toward increasing benefit with more recent *Corresponding author. trials examining post-operative radiation [7]. In node ‘This report was presented at ASTRO October,1995in Miami, positive patients, one report suggeststhat post-operative Florida. led 0167-8140/97/$17.00 0 1997ElsevierScience IrelandLtd. All rightsresen PII

SO167-8140~96~01860-9

18

D.K. Gaffney

et al. I Radiotherapy

irradiation may decrease distant metastases [5]. The benefit of treating the internal mammary (IM) nodes has been disputed; nonetheless, some authors have argued for a survival benefit with treatment to the IM nodes in selected patients [3]. Also, radiotherapy to the IM nodes can be morbid as evidenced by the 62% increase in cardiacspecific mortality for patients who received post-operative radiotherapy versus controls [7]. In one study patients who received adjuvant radiation for left-sided lesions with photons had a relative hazard of death due to ischemic heart disease of 3.2 (P
2. Methods Patients were treated from February of 1980 through December of 1993. Initially (1980-1989) electron arc was restricted to treating patients who, when planned for tangential photon treatment, had an excess of heart and lung within the irradiatied volume. Since 1989, most eligible patients were treated with the arc technique. Clinical endpoints were evaluable through December of 1994. The total population included 139 women and one man. Three patients were treated to both chest walls (two

and Oncology Table 1 Indication

42 (1997)

17-24

for treatment Stage

Indication Adjuvant

(no residual

disease) I IIA IIB IIIA IIIB Unknown

Recurrence I IIA IIB IIIA IIIB Unknown Residual

disease IIB IIIA IIIB

patients

(n)

90 1 22 32 23 11 1 33 I 10 1 5 6 4 17 4 6 I

concurrently, and one sequentially), thus, a total of 143 chest walls were treated. The indication for treatment is outlined in Table 1. The majority of patients (n=90) were treated in the adjuvant setting. Thirty-three patients were treated for recurrent disease and the remainder of the study population included patients treated after an incomplete resection (n = 15) or for primary radiation (n=2) in the setting of unresectable disease. Patient characteristics are listed in Table 2. Patients ranged in age from 22 to 82 years with a mean of 56 years. The majority of patients were treated with a two-field technique; that is, one field included the chest wall with an electron arc irradiation port and an anterior supraclavicular (photon) field that encompassed the high axilla. The third field, a posterior axillary boost, was used at the discretion of the treating radiation oncologist. Fifteen patients were treated after reconstruction of a breast mound on the chest wall. The technique of post-mastectomy electron arc irradiation has been described in detail in previous reports [1820,25,37]. Briefly, patients underwent computed tomography of the chest in the treatment position on the day of simulation. This would allow calculation for the internal mammary chain nodal depth, thickness of the chest wall (skin-surface to lung) as well as the change in contour in the cephalad/caudad dimension. To compensate for changes in this dimension, secondary collimators were customized for each patient [ 181. The treatment volume on the chest wall was outlined by the radiation oncologist and included frequently an irregular-shaped contour to encompass fully surgical scars and drain-sites as needed. For each patient, a plaster cast was constructed that rested on the treatment table and was subsequently covered with Lipowitz metal to provide tertiary collimation. Wax bolus was frequently customized to each patient to provide a

D.K. Table 2 Patient characteristics Characteristics

GafJney

et al. / Radiotherapy

(n= 140) Mean

Tumor size (cm) 4.0 No. of positive axillary lymph nodes 6.5 No. of lymph nodes removed 17.9 Follow-up interval (months) 49 Dose (cGy) 5289 DPF (cGy) 188 No. of fields 2.1 As 56 Stage I 8 IIA 32 IIB 37 IIIA 34 IIIB 24 Unknown 5 T Stage 1 27 2 52 3 28 4 25 Missing 8 Histology IDC 62 IDC, DCIS 43 IDC, ILC 2 ILC 9 ILC, LCIS 3 Grade 1 2 2 16 3 41 ER positive 88 Adriamycin 39 Hormones 80 Chemotherapy 114 Both (chemo and hormones) 57 Post reconstruction 15 Left side 85 No. of 1st degree relatives with 28 breast cancer

or n

S.D.

Range

2.7 6.8 7.1 45 651 17 0.6 13

0.4-15 O-29 2-41 12-173 2380-7050 150-225 l-3 22-82

smooth contour and compensate for lack of tissue in the axial plane. In the first three years of the study (19801983), the standard fraction for chest wall irradiation was 225 cGy 4 days per week. In 1984, a 5 fraction per week regimen was adopted and most patients were treated at 1.8 Gy daily, 5 days a week to a dose of 50.4 Gy. In the setting of microscopic or gross residual disease, a portion of chest wall was frequently boosted to a higher dose. Isodose plots were obtained at multiple levels for all patients. The rotational therapy was divided into three segments of approximately 40 degrees each. For each rotational segment a customized secondary collimator was used [ 181. The treatments were designed by selecting electron energies and placement of customized wax bolus to have the 80% isodose surface conform to the curved, pleural surface. Typically 9, 12 or 16 MeV electrons were used on the medial segment to ensure coverage of the

and Oncology

42 (1997)

17-24

19

internal mammary nodes and 6 or 9 MeV electrons were used on the lateral segments. Statistical methods utilized actuarial calculations according to the Kaplan-Meier method [21]. Further prognostic modeling was performed primarily by univariable Cox regression analysis, as missing value patterns substantially decreased the numbers of patients available for multivariable analysis [9,21,34].

3. Results In Fig. lA-C, cause-specific survival, local-regional control and freedom from distant failure is described. The minimum and mean follow-up was 1 year, and 49 months, respectively. All patients had advanced disease: T-stages 1, 2, 3 and 4 represented 21%, 39%, 21% and 19% of the study population respectively, with a mean number of positive axillary lymph nodes of 6.5 (range, O-29). Causespecific survival, local-regional control and freedom from distant failure for the 90 patients treated in the adjuvant setting is shown in Fig. 1A. Five- and lo-year local control rates were 91%. Of the seven local-regional failures, four

ye&Et----J-; A B

hT!L----------

C

.----.--_-.I.-. 0

50

100 Time (Months)

150

200

Fig. 1. Actuarial rates for local-regional control (- - -), freedom from ) are shown for distant failure (- . -), and cause-specific survival (adjuvant (A), residual disease (B), and recurrent disease patients (C). The 5-year values in per cent are shown inset, adjacent to each curve, and the number of patients at risk at 5 years is shown in parentheses.

20

D.K. Gafiey

et al. I Radiotherapy

occurred in the chest wall, yielding a crude chest wall control rate of 96%. For patients in the adjuvant setting who had a local failure the median tumor size was 3.8 cm (range, O-8 cm), and the average number of positive axillary lymph nodes was 15 (range, l-29). In addition, cause-specific survival and freedom from distant failure was 64% and 60%, respectively, at 10 years. Fig. 1B shows results for patients irradiated for residual disease (n= 15) or as primary treatment (n=2). In Fig. lC, 5 and lo-year actuarial values are given for patients who were treated for recurrent disease usually following surgical resection. These data represent all patients who were irradiated for recurrent disease and consequently do not represent patients who developed chest wall failure as the initial site of disease failure. In patients who had a local failure after being treated for recurrent disease, the average tumor size was 6 cm (range, 2.2-10 cm) and the average number of positive lymph nodes was 5 (range, O-16). For recurrent disease, a local-regional control rate of 63% at 5 years is similar to rates obtained with photon techniques

[161. Prognostic factors that were examined in univariate Cox regression analysis included T-stage, size, number of positive lymph nodes, number of total lymph nodes, age, histology, grade, receptor status, hormones (tamoxifen, in most cases), adriamycin, chemotherapy, chemotherapy and hormones used simultaneously, total dose, dose per fraction, number of fields, treatment post-reconstruction, leftsided lesion, number of first degree relatives with breast cancer, site of recurrence, and type of biopsy performed (excisional vs. incisional) for patients with recurrent disease. When patients in the adjuvant setting were evaluated for local-regional control, only the number of positive lymph nodes (P=O.O37) and dose (P=O.O19) were significant. In the setting of recurrent disease, receipt of adriamycin portended a less favorable local-regional control rate (P
and Oncology

42 (1997)

Table 3 Sites of initial

failure

17-24

(%, n= 140)

Site

Adjuvant

Residual

Recurrent

Bone Chest wall Lung Liver Brain Axilla SC node Contralat. SC Neck Arm Pleural effusion Scalp Unknown

13 3 4 3 2 1 1 1 1 1 1 1 1

18 11 6 18

21 15 15 3 3

SC refers

to supraclavicular

-

-

-

3

region.

distant metastases. The ultimate crude failure rates for the chest wall (volume encompassed by the electron arc) were 4/90 (4%) in the adjuvant group, 2117 (12%) in the recurrent disease group, and lo/33 (30%) in the residual disease group. For all patients, the mean time to localregional failure was 22 months (range, 1-134 months), and only one patient failed after 38 months. Three patients were treated to both chest walls (2 simultaneously and 1 sequentially), and all three had in-field failures (Table 4). The high failure rate in this population was likely attributTable 4 Analysis of local-regional lymph nodes, and size Patient Adjuvant 1 2* 3 4 5 6 I Residual 8* 9 Recurrent 10 11 12 13 14 15* 16 17 18 19

failures:

Stage

T stage, number T-stage

of positive

axillary

Size (cm)

No. positive

-

29 20 14 16 11 1 17

LN

setting IIA IIIA IIA IIIA IIIA IIB IRA

8 1.8 6.5 1.5 2.0 3.0

disease IIIB IIIB

4d 4d

6 10

23 15

IIA IIIB IIIB Unknown IIIB IIIB IIA IIB IIIB IRA

2 4d 4b

3 -

0 9 16 0 4 0 5 6 9

disease

5

X

4a 4d 2 2 4a 3

2.2 10 10

-, indicates the data was not available. x, indicates the T stage was not specified. *Indicates the patient had bilateral breast cancer and were treated to both chest walls. Crude local-regional control rates for stages I, IIA, IIB, IRA, and RIB were 100% (8/8), 91% (29/32), 95% (35/37), 83% (30/34), and 71% (17/24), respectively.

D.K.

Gafsney

et al. I Radiotherapy

able to poor pathologic features since two patients had T4d disease and the third patient had T3 and T2 lesions with 20 positive axillary lymph nodes. Fifteen patients were treated post-reconstruction, and 12 are alive without evidence of disease. One patient treated for recurrent disease with a disease-free interval of 17 months failed in-field (chest wall) 34 months after 61.2 Gy was delivered. Original tumor size was 10 cm with 9/21 axillary lymph nodes positive. One patient failed at 22 months in the axilla after 50.4 Gy was delivered in two fields for a T2Nl (l/3 positive axillary lymph nodes). One patient failed simultaneously in the lung and scalp 12 months after treatment. Table 5 demonstrates results for patients with inflammatory breast carcinoma. Doses used for these ten patients ranged from 45-70.5 Gy (mean 56.6 Gy). Local control was achieved in 5 / 10 patients. In only one patient was there an isolated, in-field failure as the first site of failure. Acute and chronic morbidity is portrayed in Table 6, and compare favorably with other reports [6,10,16,24]. The most frequent acute reaction in the 140 patients examined was moderate erythema. Twenty-six percent (n=37) of the patients experienced moist desquamation, and in 54% (n= 20) the reaction involved the junction with the supraclavicular field (Table 7). The development of moist desquamation was not strictly related to placement of wax bolus on the chest which was placed as a missing tissue compensator. The 7% rate of esophagitis was likely secondary to use of a supraclavicular field. The most frequent chronic complication described was hyperpigmentation seen in 17% of patients. Telangiectasia formation occurred in 13% of the patients and arm edema in 11%. The etiology of arm edema in patients treated with modified-radical mastectomy and radiation is likely multifactorial. The 11% incidence reported is not increased compared to patients treated with surgery alone [30]. Thus, the contribution of radiation therapy to arm edema in this population is likely minimal. Pulmonary dysfunction occurred in six patients. This was frequently treated with a

and Oncology

Table 6 Acute and chronic

control,

Patient

Local control

1st Failure

DFS (months)

1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

Y Y Y Y Y N N N N N

NED NED Liver Bone Bone CW (in-field) CW (out of field) CW, bone Bone Pericardium

165 22 78 23 14 28 21 14 7 0

first site of failure,

DFS, disease-free survival; NED, no evidence Local control refers to ultimate local-regional

and DFS in T4d patients

of disease; CW, chest wall. control.

17-24

21

morbidity

Morbidity Acute reactions Mild erythema Moderate erythema Brisk erythema Dry desquamation Moist desquamation Necrosis Esophagitis Fatigue Nausea Chronic complications Arm edema Hyperpigmentation Telangectasia Subcutaneous fibrosis Pulmonary dysfunction Hypothyroidism Carcinogenesis Rib fracture Ulceration RJHD FUHD,

radiation-induced

n

%

21 58 45 49 37 1 10 13 5

15 41 32 35 26 1 7 9 4

15 24 18 8 6 6 1 1 0 0

11 17 13 6 4 4 1 1 0 0

heart disease.

brief course of steroids. No patient progressed to chronic complications requiring oxygen or maintenance medications. In addition, no patients suffered radiation-induced heart disease and the target volume in all patients included the internal mammary lymph node chain. In Table 8 the rates for overall survival and localregional control are shown for this study (adjuvant setting) and seven randomized trials employing adjuvant chemotherapy and containing a postmastectomy radiation arm [ 1,13,22,23,27,29,3 1,391. These series were chosen because the inclusion criteria were homogenous and consequently, the radiation arms of the studies (as shown in Table 8) could be used to compare the efficacy of our treatment. Of the ninety patients in the adjuvant group many of them had adverse prognostic factors. The mean tumor size was 3.8 cm, with a mean of seven positive Table 7 Sites of moist

Table 5 Local-regional

42 (1997)

desquamation

Sites

n

%

JN (junction) cw SC AX JNandCW JN and AX CW and SC CW and AX SC and AX Total Any Jn

18 8 2 2 1 1 2 2 1 37 20

13 6 1 1 1 1 1 1 1 26 14

Junction (Jn) refers to the match between the supraclavicular and chest wall (CW), electron arc field. AX denotes axilla.

(SC)

field

22

D.K. Gaffney

Table 8 Trials evaluating era

postmastectomy

radiation

et al. I Radiotherapy

in the adjuvant

chemotherapy

Indication

No. points

% LRC

%OS

DFCI/JCRT SECSG Danish Trial Mayo Clinic Piedmont Assoc. Glasgow British Colombia utah

T3 or +LN >3 LN T3/4 or +LN Stage II Stage II +LN +LN Stage II and >

106 118 136 108 72 214 161 90

93 91 91 96 82 86 NR 91

10 55 68 81 60 61 63 67

refers to axillary

lymph

node positivity.

axillary lymph nodes. Nineteen patients had T3 tumors, and 12 had T4 tumors. Fourteen patients were pathologically node negative.

4. Discussion Electron arc irradiation of the post-mastectomy chest wall has been in use for irradiation of the chest wall at the University of Utah since 1980. The only other lengthy series describing electron arc irradiation of the post-mastectomy chest wall has been by Herbolsheimer et al., in which data on 117 patients were published [17]. Their rate of local-regional recurrence was 4.3%, and moderate erythematous reaction of the skin was the most frequent acute side effect. These authors also conclude that the time commitment for the treatment planning, given adequate experience, is comparable to other techniques. In our series, of 90 consecutive advanced local-regional breast cancer patients irradiated as adjuvant to modified radical mastectomy a local-regional control rate of 91% at 10 years, and a 4% chest wall recurrence rate is consistent with other published reports [1,13,17,22,23,27,29,31,39]. In seven randomized trials testing the value of post-mastectomy radiation therapy in conjunction with adjuvant chemotherapy, local-regional control rates in the radiation arm, varied from 4% to 18% [1,13,22,23,27,29,31]. The reduction in risk of local-regional failure with electron arc irradiation versus adjuvant chemotherapy is apparent (Table 9) [ 121. In our study, primary tumor size greater than 5 cm did not increase the local-regional failure rate after being separated according to nodal status (Table 9). Fowble et al. also observed that when greater than seven nodes were positive, tumor size had no effect [12]. Lung dose volume histogram analysis has demonstrated that electron arc therapy results in a statistically significant decreasein dose to lung parenchyma compared to photon tangent techniques [26]. Our data and the data of Herbolsheimeret al. suggestthat there is a low likelihood of lung damagewith the electron arc technique [17]. Although the numbers of patients is relatively small (n= 140) and the

42 (1997)

Table 9 Effect of tumor Tumor

Institute

+LN

and Oncology

O-3N+, O-3N+, 4-7N+, 4-7N+, >7N+, >7N+,

size/nodal

17-24

size and nodal status on local-regional status

TS<5 cm TSz5 cm TS<5 cm TSz5 cm TS<5 cm TS25 cm

Current

series

recurrence Fowble

No. LRFlN

%LRF

%LRF

1126 0110 O/23 O/6 4120 1113

4 0 0 0 20 8

6 12 10 31 15 15

et al. [ 121

No. LRF refers to number of patients with local-regional failure as first site of failure. N is number of patients. Two patients had simultaneous local and distant failure and they were included, and 11 patients were node negative. Patients evaluable were obtained from the adjuvant (85) and residual disease (13) categories (n=98). Patients with unresectable disease and inflammatory carcinoma were excluded. The column on the right is obtained from Fowble et al. [12] and is the LRF percentages for 622 node positive patients who received adjuvant chemotherapy alone.

follow-up is limited to 14 years, electron arc irradiation appearsto be safe and effective. Previous authors have argued for the inclusion of the internal mammary nodes within the treatment volume [3]. The meta-analysisperformed by Cuzick et al. suggeststhat a survival benefit for post-mastectomy chest wall irradiation may be apparent, however, it clearly may be technique-dependent [7,8]. If the IM nodes are to be treated, well planned electron arc therapy allows for this to be done with no match line in the chest wall and with good control of depth of treatment volume over underlying heart and lung. Consequently, it seemsreasonableto perform extensive treatment planning in these patients, many of whom have a relatively favorable prognosis. Radiation-induced heart disease likely contributed to decreased survival results in early post-mastectomy radiation trials [8,35,36], and was not observed in this study. The pathophysiology of irradiated skin has been well described [2,38], and moist desquamationin breast cancer patients has been extensively evaluated [38]. A variety of fraction schemeswere analyzed. For patients treated at 1.75-2.0 Gy per day, 5 days a week, to a total dose of 44.4-52.4 Gy, 41% (541132) of patients developed moist desquamation.Moist desquamation developed in 26% of patients in our study. The site of moist desquamationwas analyzed and although well represented it was not restricted to the matchline between the supraclavicular and electron arc field. As described by Olivotto the use of a supraclavicular field decreasesthe overall cosmetic result [28]. In somecases,but not exclusively, moist desquamation and subsequent telangiectasia formation occurred under the wax compensatingbolus. Previously, it has been demonstratedthat surface (or skin doses)are less with the electron arc technique than with en face electron fields

W31. Radiation therapy is feasible after breast reconstruction [ 15,331. Fifteen patients were treated after reconstruction to the breast. Although the follow-up on these women is

D.K. Gaffney

et al. I Radiotherapy

relatively short, they have exhibited good local-regional control (13/ 15). In a recent dosimetric analysis, studies with a breast phantom demonstrated isodose constriction at the superior surface of the reconstructed breast mound due to the tangential effect of the beam [20]. Consequently, in certain patients irradiation on a slanted breast board may be more appropriate with elevation of the spine 20” to the supine position. In summary, we feel the advantages of electron arc irradiation include a high degree of local control with acceptable acute and long-term toxicity. Specifically, the advantages include: (1) good local control, comparable to photon techniques, (2) reasonable acute and late toxicities, (3) dose-volume histogram analyses have demonstrated decreased doses to heart and lung, (4) obviates match line problem over the chest wall, (5) IM nodes included without difficulty, and (6) relative ease of treatment with reproducible execution once planned. The procedure is flexible and allows for a wide variety of patient body physiques and treatment sites to be included in the treatment volume. With routine application, the investment in time to perform the required procedures is not excessive in light of the demanding task of matching fields in an area of high risk. In addition, if post-mastectomy irradiation is going to contribute to survival, it has been demonstrated that irradiation technique will be an important contributing factor to limit late toxicities attributable to radiation therapy [5,7,8].

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