Therapeutic factors influencing the cosmetic outcome and late complications in the conservative...

lm. J Radmion Onmlo~y Biol Phw., Vol. 21. pp. 285-292 Printed in the U.S.A All rights resw~ed.

0360.3016/93 $6.00 + .oO copyright Q 1993 Pergamon Press Ltd.

??Clinical Original Contribution

THERAPEUTIC FACTORS INFLUENCING THE COSMETIC OUTCOME AND LATE COMPLICATIONS IN THE CONSERVATIVE MANAGEMENT

OF EARLY BREAST CANCER

RAJIV SARIN, M.D. DNBR,* KETAYUN A. DINSHAW, D.M.R.T. (Lond), F.R.C.R. (Land),* SHYAM K. SHRIVASTAVA, M.D. DNBR,* VINAY SHARMA, M.D.*

AND SHIVAJI M. DEORE, PH.D., Dip.RP.+

*Departments of Radiation Oncology and +Medical Physics, Tata Memorial Hospital, Parel, Bombay-4000 12, India

Purpose: To investigate the impact of clinical and physical parameters on the cosmetic result and complications, incancer breast treated with conservative surgery and definitive irradiation. Methods and Materials: Between October 1980 and December 1990, 289 patients were treated with lumpectomy and/or axiky dissection, radical irradiation with or without adjuvant therapy. The radiation therapy technique consisted of external beam therapy followed by an k-192 implant or electron beam boost. Univariate and multivariate analysis were used to evaluate the correlation between multiple factors affecting the cosmetic outcome and the complications. Results: Of 289 patients, cosmesis was evaluable in 285 and recorded as excellent to good in 226 (79%), fair in 35 (12%), and poor in 24 (9%). On multivariate analysis of these results, a high dose per fraction (p = .0018), and use of electrons as boost to the tumor bed (p = .OOl) were found to be significant. When patients boosted with electrons were excluded, a high boost dose (p = .0433) was also found significant. Fifteen (5%) patients developed severe late radiation sequelae and 14 (5%) moderate or severe arm edema. On multivariate analysis only dose per fraction of 2.5 Gy (p c .OOOl) and higher boost doses (p = .017) were significant. Conclusion: In 289 patients of early breast cancer treated with conservative surgery and radical irradiation, multivariate analysis suggests that higher dose per fraction with teletherapy and higher brachytherapy boost dose adversely affect cosmesis and contribute to the late complications.

Early breast cancer, Definitive radiotherapy, Cosmesis, Complications.

INTRODUCI’ION

The strategy of breast conservation using limited surgery and definitive irradiation for early stage breast cancer is based on the premise that women treated in such fashion would have equivalent disease control and survival chances along with a better body image and probably lesser

Now that it has been unequivocally proven in a number of prospective trials (2, 13, 20, 27, 31) that conservative surgery with definitive irradiation is comparable to radical

psychological distress compared to those undergoing rad-

surgery in terms of disease control and survival, the focus

ical surgery.

is on the quality of breast conservation. This quality of conservation is determined by the cosmetic outcome, fre- quency, and severity of complications and the psychological advantage or disadvantage which the patient de- rives from better body image and cosmesis and treatment complications. A number of therapeutic factors have been

associated with adverse cosmetic outcome and late complications in some recent reports ( 1, 7, 12, 14, 32).

In this study of conservative management for Stage I and II breast cancer, a number of therapeutic factors were gradually refined in the initial few years with the aim of improving the cosmetic outcome and reducing late complications. Various clinical and treatment parameters for their possible adverse effect over cosmesis and late complications were analyzed.

METHODS AND MATERIALS

Between October 1980 and December 1990, 289 fe- males with pathological Stages I and II breast cancer were managed with conservative surgery and radical radiation therapy with or without systemic adjuvant therapy at the Tata Memorial Hospital, Bombay. Patients with large (> 5 cm) or multicentric tumors or with diffuse micro-

Reprint request to: Dr. K. A. Dinshaw.

285

Accepted for publication 8 June 1993.

286 1. J. Radiation Oncology 0 Biology 0 Physics Volume 27, Number 2, 1993

calcifications were excluded. A written consent was ob- tained from all patients after explaining to them the nature

terior field to the internal mammary plus supraclavicular

of the procedures to be performed. area in 120 (4 1%) cases and the internal mammary, supraclavicular plus axillary area in 43 ( 15%) cases.

The mean and median age were 42 and 41 years, respectively, with a range of 19 to 79 years. The upper outer quadrant was the commonest primary site seen in 125 (43%) patients, followed by the upper inner quadrant in 80 (28%), lower outer quadrant in 33 (1 l%), lower inner quadrant in 30 (lo%), axillary tail in 16 (6%), and the central area in 5 (2%) patients.

All patients underwent a wide excision of the primary with a l-2 cm grossly normal rim of breast tissue. Further, 152 (52%) patients underwent a complete axillary dissection from level I to III and 118 (4 1%) had only level I and II axillary dissection. In a small group of 2 1 (7%) patients no axillary node dissection was performed.

This was followed by a tumor bed boost with an interstitial iridium-192 implant in 273 (95%) patients. In a small group of 15 (5%) patients the tumor bed boost was given with 8 or 11 MeV electron beams. Only in one patient no tumor bed boost was delivered. The boost dose in the first few years were variable and generally higher than 20 Gy. Subsequently the boost doses were uniformly reduced to 15 Gy for Tl and 20 Gy for T2 tumors. For 117 Tl tumors the median and mean boost doses were 15 Gy and 16.8 Gy (S.D. -t 4.5) respectively, with a range from 10 to 30 Gy. For 171 T2 tumors the median and mean boost doses were 20 Gy and 21.5 Gy (S.D. f 3.7) with a range from 10 to 30 Gy.

As per the pathological UICC TNM staging (5), 83 (29%) were Stage I (TlNO) and 206 (7 1%) were Stage II (TlNI: 35, T2NO: 87 and T2Nl: 84). Overall 118 (41%) had pathological T 1 tumors and the remaining 17 1(59%) had T2 tumors. The radiation therapy technique was gradually refined in the initial few years to optimize the cosmetic outcome and to minimize the complications. External beam irradiation was given to the whole breast with parallel opposed medial and lateral tangential beams. The medial tangential field extended l-2 cm across the midline with the lateral tangential portal at the mid axillary line. The superior border was about 2 cm above the clavicle and the inferior border was 1 cm below the in- framammary sulcus. The portals were simulated to ensure minimum lung tissue irradiation. No bolus was used over the scar. The initial 37 (13%) patients were treated on a telecobalt unit at 60 SSD with a breast cone that blocked half the beam, without any wedges. The central axis was at the posterior border of the fields where interfield separation is greater than at the centre of the breast. The prescription of dose along this plane without wedges led to 10% to 20% increase in the dose in the nipple region over the actual prescribed dose. The remaining 252 (87%) patients were treated with 6MV photons’ with an isocentric technique at 100 cm source axis distance and an appropriate wedge pair to compensate for the breast contour. The dose was prescribed at the midplane along the central axis. The dose distribution was homogenous in all patients treated on the 6 MV linear accelerator consequent to the isocentric technique used along with appropriate wedges.

For most of this study it was the practice to implant the entire tumor-bearing quadrant including the nipple areola complex using two or three planes. However, during the last 2 years the implant volume was restricted to a 2 cm margin around the tumor. Source localization was done with orthogonal simulator x-rays. The Paris system of dosimetry was followed in prescribing the doses at 85% of the basal dose rate at the central plane. Computer iso- dose distributions were generated in all the patients. The total dose to the tumor bed was 60 Gy or more in all but three patients.

Systemic adjuvant therapy in the form of chemotherapy using cyclophosphamide, methotrexate and 5-flurouracil (CMF) or cyclophosphamide, doxorubicin and 5-flurouracil (CAF) regimen and/or tamoxifen were given to 124 patients. (Chemotherapy alone in 76, chemotherapy with tamoxifen in 15, and tamoxifen alone to 33.)

All patients were followed up regularly at 3 to 6 month intervals and were evaluated for disease control, cosmesis, and treatment complications. For cosmetic assessment, the criteria suggested by Harris et al., (16) as described below were followed. EXCELLENT: Treated breast nearly identical to the untreated breast. GOOD: Treated breast slightly different from the un-treated breast. FAIR: Treated breast clearly different from the untreated breast but not seriously distorted. POOR: Treated breast is seriously distorted. However, we have grouped together the excellent and good cosmetic results in this study since at times it was difficult to clearly differentiate between these two.

The initial 24 (8%) patients were treated with a daily dose of 2.5 Gy per fraction. This was then reduced to 2 Gy in five patients and then 1.8 Gy in the remaining 260 cases. Treatment was given daily to both fields, 5 days in a week. The total dose was 45 Gy in 266 (92%) of patients, 40 Gy in 18 (6%), and 50 Gy in 5 (2%) patients.

A peripheral lymphatic boost of 15 Gy in 6 fractions at the rate of 2.5 Gy per day was given with a single an-

The late radiation sequalae of breast fibrosis and telangiectasia were graded as none, mild, moderate, and severe. Lymphoedema of the arm was similarly graded as per the criteria used by Bates (3). Mild: lymphoedema of the arm requiring no alteration of the sleeve sizes. Mod- erate: lymphoedema of the arm necessitating a large sleeve size. Severe: lymphoedema of the arm causing serious in- capacity.

’ Linear Accelerator, CLINAC-6, Varian.

Early breast cancer 0 R. SARIN ef al. 281

RESULTS

In this paper we have analyzed the cosmetic outcome and complications following conservative therapy in 289 women with Stage I and II breast cancers and the factors influencing them. At the time of this analysis in June 1992, the median and mean follow-up was 43 and 50 months, respectively, with a range from 4 to 137 months. Seventeen (6%) patients were lost to follow-up after a median time of 22 months.

Of the 289 patients, cosmesis was evaluable in 285 patients as it was not recorded in the remaining four patients. Of these 285 evaluable cases, the cosmesis recorded at last follow-up was excellent to good in 226 (79%), fair in 35 (12%), and poor in 24 (9%). A fair to poor cosmesis ob-

served in 59 (2 1%) patients was considered as a cosmetic failure.

Fifteen (5%) patients developed severe late radiation sequalae in the breast (severe fibrosis in 8, marked telangiectasia in 2, fat necrosis in 1 and radiation necrosis in 4 patients.) In addition, 14 (5%) patients developed moderate or severe arm edema and seven (2%) patients developed breast edema.

Chi-square tests (Mantel Hanzel corrected) (2 1) were used to measure the association of various clinical and treatment variables. Statistically significant (p < .05) factors for cosmetic failure (Table 1) on unifactorial analysis were 2.5 Gy fraction size (p < .OOOO 1 ), higher boost dose (p < .OOOOl), treatment on telecobalt machine without wedges (Q < .OOOO I), boost delivered by an electron beam

Table 1. Clinical and therapeutic variables affecting cosmetic outcome in 285 patients

Variables (no. pts.)

Median follow-up (months)

Excellent/good cosmesis

No. @)

226 (79)

Fair/poor cosmesis

No. (W) P

59 (21) value

< 40 years (141) > 40 years (144)

Tumor location Lower outer quadrant (33) Others (252)

Tumor size T-l (117) T-2 (168)

Radiation technique Cobalt, no wedges (36) 6 MV with wedges (249)

Site of external RT Breast only (122) Breast, IMC, SC (120) Breast, IMC, SC, Axilla (43)

Dose/fraction 1.8-2.0 Gy (26 1) 2.5 Gy (24)

Boost type* Electrons ( 15) (Iridium implant (2 19)

Boost dose < t _ 15Gy (100) > 15-20 Gy (133) > 20-26 Gy (19) > 26-30 Gy (32)

Implant dose rate/hour Not recorded (3) 20-29 cGy/hr. (17) 30-60 cGY/hr. (198) 6 l-90 cGy/hr. (36) 91-160 cGy/hr. (15)

Adjuvant theory Not given (163) Chemo and/or hormone (90) Hormone only (32)

39 109 36 117

35 21 36 205

33 101 38 125

85 15 34 211

28 101 38 96 39 29

34 220 93 6

73 6 36 219

30 89 33 110 71 12 80 14

26 3 43 12 33 167 42 31 98 6

43 126 30 73 26 27

(77) 32 (80) 27

(64) 12 (81) 47

(86) 16 (74) 43

(42) 21 (85) 38

(83) 21 (80) 24 (67) 14

(84) 41 (25) 18

(40) 9 (81) 50

(89) 11 (83) 23 (63) 7 (44) 18

(100) 0 (71) 5 (84) 31 (86) 5 (40) 9

(77) 37 (81) 17 (84) 5

(23) (20)

(36) (19)

(14) (26)

(58) (15)

(17) (20) (33)

(16) (75)

(60) (19)

(11) (17) (37) (56)

(00) (29) (16) (14) (60)

(23) (19) (16)

0.499

0.017

0.016

< 0.00001

0.044

0.00001

0.0004

< 0.00001

0.002

0.58

IMC = Internal mammary chain; SC = Supra clavicular fossa. * One patient did not receive a boost.


(p < .00004), T2 tumors (p = .016), tumors situated in the lower outer quadrants (p = .O 17), implant dose rate > 90 cGy/hr (p < .002), and the use of a peripheral lymphatic area boost by a separate portal (p = .044).

All the variables that were statistically significant on the Chi-Square test were further subjected to a multiple regression analysis using the SPSS/PC+ advanced statis- tical software ( 19). Of the many variables considered in the multivariate analysis only two factors retained statis- tical significance as shown in Table 2. These are a high dose per fraction of 2.5 Gy (p = .OOOS) and use of the electron beam for boosting the tumor bed (p = .OOl). When the 15 cases boosted with electrons were excluded from the multivariate model, then the factors found significant were high dose per fraction of 2.5 Gy (p = .0014) and a high boost dose (p = .0433).

wedges on a telecobalt unit and > 20 Gy boost dose were all highly significant (p < .OOOl) adverse therapeutic factors (ATF) for cosmetic failure and severe late radiation sequalae in the unifactorial analysis as shown in Table 5. The incidence of cosmetic failure increased from 14% when none of these three ATF were present to 45% when any one of these three ATF were present and 76% when all three ATF were present (p < .OOO 1). Similarly the risk of severe late radiation sequalae in the breast increased from 1% when none of these three ATF were present to 18% when any one of these three ATF were present to 45% when all these three ATF were present (p < .OOOl).

DISCUSSION

Similarly the therapeutic factors were analyzed for any possible association with the development of severe late radiation sequalae in the breast (Table 3) and development of arm and breast edema (Table 4). On unifactorial analysis for late radiation sequalae in the breast (severe fibrosis, marked telangiectasia, fat necrosis, and radiation necrosis), the factors found significant were a dose per fraction of 2.5 Gy (p < .OOOOl), boost doses higher than 20 Gy (p < .OOOO l), treatment on a telecobalt unit without wedges (p < .OOOOl), and an implant dose rate > 90 cGy/hr (p = .014). Surprisingly, the complication rate was significantly higher in the patients who were not given any systemic adjuvant therapy (p = .048) as shown in Table 3. However in the multivariate analysis only two treatment parameters were independently significant for severe late radiation sequalae in the breast as shown in Table 2. These are a dose per fraction of 2.5 Gy (p < .OOOl) and higher boost doses (p = .O 17).

The results of this study indicate that the cosmetic outcome and late breast sequalae are intimately related to a number of therapeutic factors, many of which have been confirmed in previous studies.

Unexpectedly, no significant correlation was noted between arm or breast edema and therapeutic factors like extent of axillary surgery and the use of peripheral lymphatic area boost as shown in Table 4.

The use of 2.5 Gy dose per fraction, treatment without

Similar to many other reports (4, 18, 25, 32), we have not found any significant association between young age and better cosmesis. However, Steeves et al. (28) have noted better cosmesis in younger women. The influence of the site of primary tumor in breast over cosmesis is controversial. While a few studies (4, 18, 25) have failed to find any significant impact of tumor site in the breast over cosmesis, inferior cosmetic outcome was observed in lower half tumors by Habibollai et al. (p -c .OO 1) (15), inner quadrant tumors by Steeves et al. (28), and lower inner quadrant tumors by van Limbergen et al. (30) in a multivariate analysis (p = .018 1). We have also found a significant correlation (p = .017) between lower outer quadrant tumors and cosmetic failure on univariate analysis. However, when other therapeutic factors were also considered in the multivariate model, then the site of tumor was no longer significant for cosmetic failure.

The detrimental effect of the extent of surgery over cosmesis has been born out in a number of studies (23, 26,

Table 2. Results of multiple regression analysis for cosmetic failure and late severe radiation sequelae in the breast

Fair/poor cosmesis

All cases Implant cases Variables (284)* (269)*

Location 0.241 0.387 Tumor size 0.389 0.969 Cobalt, no wedges 0.292 0.801 Dose per fraction 0.0008 0.0014 Irradiation 0.564 0.428 Boost dose 0.711 0.0433 Boost type 0.001 - Implant dose rate 0.284 0.711 Adjuvant therapy - -

* Four patients excluded in whom cosmesis was not recorded. + One patient excluded in multivariate analysis as no tumor bed boost was given.

Late severe rad. sequelae, all cases

(288)’

0.162 0.913 0.076

< 0.0001 0.151 0.017 0.996 0.351 0.43 1

Early breast cancer 0 R. SARIN et a/. 289

Table 3. Therapeutic factors affecting late radiation sequelae in the breast in 289 patients

Late severe radiation seouelae in breast

Variables (no. pts..)

Median follow-up (months)

No.

15/289

(%)

(5%) P

value

Radiation technique Cobalt, no wedges (37) 6 MV with wedges (252)

Site of external radiation therapy Breast only (124) Breast, IMC, SC (122) Breast, IMC. SC, axilla (43)

Dose/fraction 1.8-2 Gy (265) 2.5 Gy (24)

Boost type* Electrons (15) Iridium implant (273)

Boost dose lo-15 Gy (102) > 15-20 Gy (136) > 20-26 Gy (19) > 26-30 Gy (32)

Implant dose rate/hour Not recorded (3) 20-29 cGy/hr (17) 30-60 cGy/hr (201) 6 l-90 cGy/hr (36) 91-160 cGy/hr (15)

Adjuvant therapy Not given (154) Chemo and/or hormone (91) Only hormone (33)

85 36

29 3 (2) 38 8 (7) 0.0512 39 A (9)

34 93

73 39

30 33 77 80

26 43 34 42 98

43 12 (8) 30 3 (3) 0.0483 26 0 (0)

10 5

5 10

1 (6) 14 (5)

(27) (2)

< 0.00001

C-4 (42)

< o.oooo1

0.74

(0) (2)

(21) < 0.00001

(25)

(0) (1) (4) 0.014 (3)

(27)

IMC = Internal mammary chain; SC = supraclavicular fossa. * One patient did not receive a boost.

30). Inferior cosmetic results were noted by Ryoo et al. (26) with > 50 cm3 of specimen size (p = .017) and Oli- votto et al. (23) with > 70 cm3 of breast tissue resection (p = .03). van Limbergen et al. (30) also noted better cosmesis in patients treated with tumorectomy as com-

pared to those who underwent segmentectomy (p = .05). The exact volume of breast tissue resected was not rou- tinely recorded in our study. However, we have analyzed the correlation between pathological tumor size and cosmesis. The pathological tumor size should possibly be in-

Table 4. Therapeutic factors affecting moderate/severe arm and breast edema in 289 patients

Variables (no. pts)

Type of surgery Only wide excision (2 1) Wide excision, low axillary dissection ( 118) Wide excision, full axillary dissection ( 150)

Site of external radiation therapy Breast only (124) Breast, IMC, SC (122) Breast, IMC, SC, axilla (43)

Dose/fraction 1.8-2.0 Gy (265) 2.5 Gy (24)

Median follow-up Moderate/severe edema (months) Arm + breast (a)

28 0 + 0 (0) 38 7 + 4 (9) 42 7 + 4 (7)

29 5 + 7 (10) 38 8 + 1 (7) 39 1 + 0 (2)

34 14 + 8 (8) 93 0 + 0 (0)

P value

0.326

0.291

0.142

IMC = Internal mammary chain; SC = Supraclavicular fossa.


Table 5. Factors tiecting cosmesis and late complications

Fair/poor cosmesis* Late breast

complication

No. (%I No. (%) Therapeutic factor

Telethemnv dose/fraction

591285 (21) P+ 151289 (4) P'

1.8-2 Gy 2.5 Gy (ATF)*

Teletheranv technioue

411261 (16) < .OOOl S/265 18124

(2) (75) lo/24 (42)

< .OOOl

6 MV with wedges Telecobalt without

wedges (ATF)* Boost dose

381249 < .OOOl (15) 51252 21136

(2) (58) 10137 (27) c .OOOl

lo-20 Gy (ATF)* > 20-30 Gy

None of three ATF One of three ATF Two of three ATF All three ATF

241233 (10) 31237 2515 1 (50) < .OOOl 12151 30122 1 (14) 31224 29164 (45) < .OOOl 12165 18126 (73) 1 O/26 16121 (76) 10121

< .ooOl

‘uj (18) < .Oool (38) (48)

* Cosmesis evaluable in only 285 of 289 patients. ’ p value by Chi-square test (Mantel-Haenzel corrected). * Adverse therapeutic factor for cosmesisjcomphcation.

dicative of the extent of surgical excision, as all patients underwent wide excision with a l-2 cm rim of grossly normal breast tissue. We have observed inferior cosmetic results in patients with larger tumor size that is, T2 tumors on univariate analysis (p = .017) though not on multivariate analysis. Dewar et al. ( 12) have reported that tumor size > 14 mm was the most significant factor for cosmesis in a multivariate analysis (p < .OOOOl). More recently Rose et al. (25) also noted excellent cosmetic results in only 52% of T2 tumors as opposed to 70% of Tl tumors (p = .02). Wazer et al. (32) have also found that palpable tumors had inferior cosmetic outcome as compared to non-palpable tumors (p = .046). However Beadle et al. (4) and Krishnan et al. (18) have not found any correlation between tumor size and cosmesis.

As would be expected, very high biologically equivalent radiation doses to the breast can significantly worsen the cosmetic outcome and increase late complications. Such high biologically equivalent doses could be due to higher total dose delivered to the whole breast (10, 16, 30) and to the tumor bed by a boost (4, 32), a higher dose per fraction of external beam therapy (6, 12, 30), treatment of fields on alternate days (26), high dose rates of implants and inhomogeneity and localized hot spots on match lines of external beam portals (23,26,30), failure to use wedges and increasing chest wall separation (32).

In the present study, the use of high dose per fraction of 2.5 Gy was the most significant factor for cosmetic failure and late breast complications on both univariate and multivariate analysis. Larger fraction size of 4-6 Gy have been found to produce greater fibrosis and inferior cosmesis in the study by van Limbergen et al. (30). Sim- ilarly Dewar et al. (12) have reported that a group of pa-

tients receiving breast irradiation with two tangential fields each treated on alternate days, the daily applied dose of > 3.5 Gy per fraction was very significantly related to the cosmetic outcome on multivariate analysis (p < ,Ol). Clarke et al. (6) have also reported increased incidence of fibrosis with 2.5 Gy fraction size as compared to 1.8 or 2 Gy. Ryoo et al. (26) have reported the favorable cosmetic outcome of treating both fields per day (p < .OOOl).

Since in our study whole breast doses ranged from 40 to 50 Gy, and the majority (92%) received a moderate dose of 45 Gy, we could not examine the deleterious effect of high radiation doses to the whole breast as reported by others (10, 16, 30).

In a few studies (4, 32) the use of a tumor bed boost after whole breast irradiation has significantly affected the cosmetic outcome. However, in both these studies the correlation of tumor bed boost with cosmesis has not been tested. Tumor bed boost dose higher than 20 Gy has significantly affected the cosmetic outcome and late complications in our study.

In the present study the iridium- 192 implant dose rate of > 90 cGy/hr had a significant impact over cosmesis and late breast complications on univariate analysis. However, on multivariate analysis the implant dose rate was not confirmed as an independent factor for cosmesis or complications. Mazeron et al. (22) have not found any association between implant dose rate and cosmesis. However, in their study cosmesis was evaluable in only two thirds of the treated patients and in none of these patients the dose rate exceeded 90 cGy/hr.

For optimal cosmesis the choice of the type of boost, electrons or interstitial implants remains a controversial issue. Certain studies have not found any impact from

Early breast cancer 0 R. SARIN el al. 291

the type of boost on cosmesis (6,26), some have noted a favorable cosmetic outcome with electrons (24), while others have either found or postulated better cosmesis with interstitial implants (11, 32). Though in our study patients treated with interstitial implants had significantly better cosmetic score than those receiving electron boost, we can not draw any firm conclusions. This significantly different outcome could have been caused by a bias in the selection of patients or caused by the high dose per fraction of 2.5 Gy daily used for electron boost as opposed to the continuous low dose rate of implants.

It was our practice to boost the entire quadrant for most of this study and only the patients treated in the last 2 years received boost limited to the tumor bed. Thus, we have not analyzed the influence of boost volume over cosmesis, as the two groups were not comparable because of a much limited follow-up in the latter group. While Olivotto et al. (23) noted a significant correlation between increasing implant volume and cosmetic failure, this was not confirmed in another study reported by Dewar et al. ( 12).

As has been found in most of the studies (18, 23, 26, 30), we have noted a detrimental effect of using a separate portal over the cosmesis in the univariate analysis. How- ever, on multivariate analysis it did not retain its significance.

Another factor producing unacceptable dose inhomo- geniety in some of the patients was the treatment on a telecobalt machine without wedges. As would be expected, these patients had a significantly higher cosmetic failure and late breast complications. Ryoo et al. (26) have pre- viously reported the favorable effect of using wedges on cosmesis (p < .OOOl).

The impact of adjuvant chemotherapy over the cosmetic outcome and complication rate is a controversial issue. While most studies (8, 18, 26, 28, 32) including

ours have found no correlation between the use of chemotherapy and the cosmetic outcome, some ( 1,251 have shown a significant association between the use of chemotherapy, especially concurrent chemotherapy and an inferior cosmetic outcome.

In our study, unexpectedly no correlation was noted between the extent of axillary surgery or use of a separate portal to irradiate the axilla and occurrence of lymphoedema of the arm or breast, contrary to what has been found in the majority of studies (4, 6, 9, 10, 17, 32).

The 2 1% overall incidence of fair and poor cosmesis as found in our study is comparable to the 18% to 22% incidence of fair to poor cosmesis in some other studies (4,15,28). Beadle et al. (4) observed fair and poor cosmesis in 14% of the 239 patients treated for early breast cancer, however when patients who received a boost were considered separately, 22% of these patients had fair and poor cosmesis.

Similarly, in our study if the patients treated with certain adverse therapeutic factors in the first years are excluded (Table 5) the incidence of cosmetic failure is 14% and the severe late complication rate < l%, which is comparable to the more recent studies reporting better cosmetic results (14, 18, 32).

In summary, the findings of this study highlight the detrimental effect of suboptimal radiation technique causing greater dose inhomogenity, the use of high dose per fraction in external beam irradiation and higher boost doses over the occurrence of complications in the breast.

As would be expected the therapeutic refinements car- ried out over the first few years of this study have resulted in the desired outcome of improved cosmesis with lesser complications. This data suggests that while striving for optimal local control, strict quality control should be maintained for an acceptable cosmetic outcome with minimal complications.

REFERENCES

1.

2.

3.

4.

5.

6.

Abner, A. L.; Recht, A.; Vicini, F. A.; Silver, B.; Hayes, D.; Come, S.; Harris, J. R. Cosmetic results after surgery, chemotherapy, and radiation therapy for early breast cancer. Int. J. Radiat. Oncol. Biol. Phys. 21:331-338;1991. Battelink, H.; Van Dam, F.; Van Dongen, J. Psychological effects of breast conserving therapy in comparison with radical mastectomy. Int. J. Radiat. Oncol. Biol. Phys. 11:38 l- 385;1985. Bates, T. D. The 10 year results of prospective trial of post- operative radiotherapy in 3 fractions per week versus 2 fractions per week in breast carcinoma. Brit. J. Radiol. 6 1:625- 630; 1988. Beadle, G. F.; Silver, B.; Botnick, L.; Hellman, S.; Harris, J. R. Cosmetic results following primary radiation therapy for early breast cancer. Cancer 54:29 1 l-29 18; 1984. Beahrs, H.; Henson, D. E.; Hutter, R. V. P.; Myers, M.; Eds. Manual for staging of cancer, 4th edition. Philadelphia: J. B. Lippincott, 1988.

9.

10.

Clarke, D. H.; Martinez, A. A. Identification of patients who are at high risk for locoregional breast cancer recurrence after conservative surgery and radiotherapy: A review article for surgeons, pathologists and radiation and medical on- cologists. J. Clin. Oncol. 10:474-483;1992. Danoff, B. F.; Goodman, R. L.; Glick, J. H.; Haller, D. G.; Pajak, T. F. The effect of adjuvant chemotherapy on cosmesis and complications in patients with breast carcinoma treated by definitive irradiation. Int. J. Radiat. Oncol. Biol. Phys. 9:1625-1630;1983. Danoff, B. F.; Pajak, T. F.; Solin, L. J.; Goodman, R. L. Excisional biopsy, axillary node dissection and definitive radiotherapy for stages I and II breast cancer. Int. J. Radiat. Oncol. Biol. Phys. 11:479-483;1985. Delouche, G.; Bachelot, F.; Premont, M.; Kurtz, J. M. Con- servation treatment of early breast cancer: Long term results and complications. Int. J. Radiat. Oncol. Biol. Phys. 13:29- 34;1987.

Clarke, D.; Martinez, A.; Cox, R. S. Analysis of cosmetic 11. Denham, J. W.; Hamilton, C. S.; Cross, P. Breast conser- results and complications in patients with stage I and II breast cancer treated by biopsy and irradiation. Int. J. Radiat.

vation, the problem of treating the excision site effectively: Physical criteria for the choice of technique used. Clin. On-

Oncol. Biol. Phys. 9: 1807- I8 13;1983. col. 3:250-256; 199 1.


12. Dewar, J. A.; Benhamou, S.; Benhamou, E.; Aniagada, R.; Petit, J. Y.; Fontaine, F.; Sarrazin, D. Cosmetic results following lumpectomy, axillary dissection and radiotherapy for small breast cancers. Radiother. Oncol. 12:273- 280;1988.

13. Fisher, B.; Redmond, C.; Poisson, R.; Margolese, R.; Wol- mark, N.; Wickerham, L.; Fisher, E.; Deutsch, M.; Coplan, R.; Pilch, Y.; Glass, A.; Shibita, H.; Lerner, H.; Terz, J.; Sidorovich, L. Eight year results of a random&d trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N. Et@. J. Med. 320:822-828; 1989.

14. Fowble, B. L.; Solin, L. J.; Schultz, D. J.; Goodman, R. L. Ten year results of conservative surgery and irradiation for stage I and II breast cancer. Int. J. Radiat. Oncol. Biol. Phys. 21:269-277;1991.

15. Habibollahi, F.; Mayles, H. M. 0.; Mayles, W. P. M.; Winter, P. J.; Tong, D.; Fentiman, I. S.; Chaudhary, M. A.; Hayward, J. L. Assessment of skin dose and its relation to cosmesis in the conservative treatment of breast cancer. Int. J. Radiat. Oncol. Biol. Phys. 14:291-296;1988.

16. Harris, J. R.; Levene, M. B.; Svensson, G.; Hellman, S. Analysis of cosmetic results following primary radiation therapy for stage I and II carcinoma of the breast. Int. J. Radiat. Oncol. Biol. Phys. 5:257-261;1979.

17. Kissin, M. W.; Querci della Rovere, G.; Easton, D.; West- bury, G. Risk of lymphoedema following the treatment of breast cancer. Br. J. Surg. 73:580-584;1986.

18. Krishnan, L.; Jewell, W. R.; Mansfield, C. M.; Reddy, E. K.; Thomas, J. H.; Krishnan, E. C.; Gerald, K. Cosmetic results in early breast cancer treated with lumpectomy, peri- operative interstitial irradiation and external beam radiation. Int. J. Radiat. Oncol. Biol. Phys. 15:205-211;1988.

19. Lee, E.; Desu, M. A computer program for comparing K samples with right-censored data. Comp. Prog. Biomed. 2: 3 15-32 1; 1972 (SPSS/PC + Advanced Statistics Package).

20. Lichter, A. S. Editorial: Lumpectomy and irradiation: Im- proving the outcome. J. Clin. Oncol. 10:349-351;1992.

2 1. Mantel, N. Chi square tests with one degree of freedom: Extentions of the Mantel-Haenszel procedure. JASA 58: 690-700; 1963.

22. Mazeron, J. J.; Simon, J. M.; Crook, J.; Calitchi, E.; Oth- mezguine, Y.; Bourgeois, J. P. L.; Pierquin, B. Influence of dose rate on local control of breast carcinoma treated by external beam irradiation plus Iridium 192 implant. Int. J. Radiat. Oncol. Biol. Phys. 2 1: 1173- 1177; 199 1.

23. Olivotto, I. A.; Rose, M. A.; Osteen, R. T.; Love, S.; Cady, B.; Silver, B.; Recht, A.; Harris, J. R. Late cosmetic outcome

after conservative surgery and radiotherapy: Analysis of causes of cosmetic failure. Int. J. Radiat. Oncol. Biol. Phys. 17:747-753;1989.

24. Ray, G. R.; Fish, V. J. Biopsy and definitive radiation therapy in stage I and II adenocarcinoma of the female breast. Analysis of cosmesis and the role of electron beam suppli- mentation. Int. J. Radiat. Oncol. Biol. Phys. 9:813- 818;1983.

25. Rose, M. A.; Olivotto, I.; Cady, B.; Koufman, C.; @teen, R.; Silver, B.; Recht, A.; Harris, J. R. Conservative surgery and radiation therapy for early breast cancer. Long term cosmetic results. Arch. Surg. 124: 153- 157; 1989.

26. Ryoo, M. C.; Kagan, A. R.; Wollin, M.; Tome, M. A.; Te- deschi, M. A.; Rao, A. R.; Hintz, B. L.; Kuruvilla, A. M.; Nussbaum, M.; Streeter, 0. E. Jr.; et al. Prognostic factors for recurrence and cosmesis in 393 patients after radiation therapy for early mammary carcinoma. Radiology 172:555- 559;1989.

27. Sarrazin, D.; Le, M. G.; Arrigada, R.; Contesso, G.; Fontaine, F.; Speilman, M.; Rochard, F.; Le Chevalier, T. H.; Lacour, J. Ten year results of a random&d trial comparing a conservative treatment to mastectomy in early breast cancer. Radiother. Oncol. 14: 177- 184; 1989.

28. Steeves, R. A.; Phromratanapongse, P.; Wolberg, W. H.; Tormey, D. C. Cosmesis and local control after irradiation in women treated conservatively for breast cancer. Arch. Surg. 124: 1369-I 374; 1989.

29. van Limbergen, E.; van den Bogaert, W.; van der Schueren, E.; Rijnders, A. Tumor excision and radiotherapy as primary treatment of breast cancer. Analysis of patient and treatment parameters and local control. Radiother. Oncol. 8: I-9;1987.

30. van Limbergen, E.; Rijnders, A.; van der Schueren, E.; Len& T.; Christiaens, R. Cosmetic evaluation of breast conserving treatment for mammary cancer 2: a quantitative analysis of radiation dose, fractionation schedules, and surgical treatment techniques on cosmetic results. Radiother. Oncol. 16:253-267; 1989.

31. Veronisi, U.; Banfi, A.; Del Vecchio, M.; Saccozi, R.; Cle- mente, C.; Greco, M.; Luini, A.; Marulini, E.; Masculine, G.; Rilke, F.; et al. Comparison of Halstead mastectomy with quadrentectomy, axillary dissection, and radiotherapy in early breast cancer: Long term results. Eu. J. Cancer Clin. Oncol. 22:1085-1089;1986.

32. Wazer, D. E.; DiPetrillo, T.; Schmidt-Ullrich, R.; Weld, L.; Smith, T. J.; Marchant, D. J.; Robert, N. J. Factors influencing cosmetic outcome and complication risk after conservative surgery and radiotherapy for early-stage breast carcinoma. J. Clin. Oncol. 10:356-363;1992.

Therapeutic factors influencing the cosmetic outcome and late complications in the conservative...

Documents

Transcript of Therapeutic factors influencing the cosmetic outcome and late complications in the conservative...