Eur3 Concrr, Vol. 26, No. 6, f$, 674-679, 1990. Printed tn Gmt Bhin
0277-5379190$3.00 + 0.00 0 1990PergamonPressplc
Local Control of Operable Breast Cancer after Radiotherapy Alone E. Van Limbergen, E. Van der Schueren, W. Van den Bogaert and J. Van Wing
221 patients with operable breast carcinoma stage Tis, Tl, T2, T3, NON1 were treated with radiotherapy alone without tumorectomy. The mean follow-up time was 15.5 years (range S-22). The annual risk for local recurrence was 3% during the first 5 years and 1% during the following 10 years, resulting in an actuarial local control rate of 75.4% after 15 years. The risk for local recurrence was assessed in multivariate analysis and was significantly related to the size of the tumour measured on mammography (P = 0.0002), the radiation dose administered (P = O.OOlS),the length of the split-course intervals being longer than 75 days (P= 0.001) and age (P= 0.019). Dose was related to response over a wide range as a function of tumour volume. All 18 patients with minimal tumour load (TO and Paget’s disease) treated with doses above SS Gy in 6 weeks achieved local control. S-year local control rates ranged from 40 to 100% for Tl carcinomas treated with 45-110 Gy, and from 0 to 95.3% for Tt carcinomas at the same dose. For T3 carcinomas local control varied between SOand 83% at 60-110 Gy. The risk for local failure increased by 8% per cm tumour diameter. With exclusive radiotherapy, the doses needed to provide local control rates similar to those obtained after tumorectomy and irradiation are 10 Gy higher for Tl (95% S year control) and 35 Gy higher for T2 (90% S year control). EurJ Cancer, Vol. 26, No. 6, pp. 674-679,1990.
INTRODUCTION Dr.7 .n”. ,.,.\YCrn.,r.lr. ^....- ,..... .Wllll ....t. ..,.rl:,rL,,,,.. I.,, l.,,,...,a DKutJI-L” nJCn”In~aulg;cly laulvulslapy lldL3 “FL”IIICa valid alternative to mastectomy in the treatment of operable stage I and II breast cancer [l-3]. Experience in operable breast cancer (UICC stages I, II, IIIA) treated with radiotherapy alone without tumorectomy is less extensive. In the early days of breast-conserving treatment radiotherapy alone was offered as an alternative to patients refusing mastectomy [4-61. These studies were extended into the megavoltage range, when mainly French institutions treated these patients with radiotherapy alone [7-91. High radiation doses are required for controi of breast cancer with radiotherapy alone [9-l 11. These high doses result in excessive fibrosis of normal tissues [12, 131. Therefore most centres now favour the combined treatment with surgery and radiotherapy for small breast tumors. Several groups [9, 11, 141 have shown that the possibility of breast cancer control with radiotherapy alone is related to tumour size and radiation dose. However, follow-up has been limited [9] or the dose range has been small. And the large study of Arriagada et al. [ 1l] mainly concerned patients with locally advanced rather than operable disease. We have updated the Leuven experience with more information on tumour size and dose response in patients with operable stage I, II and IIIA
breast cancer treated with radiotherapy alone. The follow-up of +l., ,..r:,..r, pG” . . . .luualy .. ..P.......IqJ” .._..__ +,& L7J TO,13 :, ll” ”_.., I,.., _.. *I..... UK panFur IICU W I” llgjFI L,,W,1 I,F .rsnm yralJ, while additional patients treated up to 1984 have been included. PATIENTS AND METHODS Patients
221 patients treated between 1967 and 1984 at the University Hospital of Leuven with radiotherapy alone for Tis, Tl, T2, T3, NON1 breast cancer have been analysed. Mean follow-up is 15.5 years (range 5-22). Most were treated before 1977 (94%). -_ __ Age ranges between 28 and 86 years (mean 5Y.4). Aii patients had undergone a Vim Silvermann needle biopsy and fine-needle aspiration cytology. The biopsy specimens and cytological slides were reviewed by J.V.W. The diagnosis of breast cancer was confirmed on biopsy in 195 cases and by cytology in 24 patients. In 2 patients both biopsy and cytological examination showed no breast cancer cells, but the clinical presentation, mammography and clinical course with metastases have confirmed the malignant character of the breast tumour. Biopsy samples were classified and graded according to the WHO classification (Table 1). All patients were reclassified according to 1987 UICC Tumouri Node/Metastases staging (Table 2). Tumour size was measured in 185 available mammograms. Radiation schedules 1967-1984 included
Correspondence to E. Van der Schueren, Department of Radiotherapy, Universitair Ziekenhuis, St RafaCl, B-3000 Leuven, Belgium. E. Van Limbergen, E. Van der Schueren, W. Van den Bogaert are at the Department of Radiotherapy and J. Van Wing is at the Department of Pathology, University Hospital, Leuven, Belgium.
the period of early experiences with breast-conserving therapy in Leuven. In the first patients treated, low radiation doses were used (below 50 Gy). Gradually, higher doses were administered, up to 96 Gy in 1976. Later,
674
Local Control of Operable Breast Cancer Table 1. Operable breast cancer treated with radiotherapy alone (WHO classification) Invasive Morbus Paget Ductular GI GII GIII Not graded Lobular Medullary Colloid Malignant nipple fluid No histological confirmation*
0 182 32 70 42 38 17 2 1
Total
204
Non-invasive 14 1
2 2 17
doses were lowered to 65 Gy. The doses have been recalculated for all patients and specified at midline depth on the central axis of the beam, as is recommended by the ICRU (International Commission on Radiation Units and Measurements) (Table 3). 185 patients received 2 X 6 Gy (n = 182) or 2 x 4 Gy (n = 3) with 13-15 MeV of a Brown Bovery Betatron on limited fields, as a ‘prebiopric flash’ before biopsy. Totai doses to the whoie breast range between’36 and 85 Gy. Most patients have received either about 40 Gy in 4 weeks (n = 33), 60-65 Gy in 8-10 weeks (n = 164), with fraction sizes ranging between 200 and 225 cGy per day. 15 patients have received higher total doses to the breast (up to 85 Gy). After the breast irradiation, booster doses on limited fields were administered to the primary tumour area in 146 patients, usually with 15 MeV electrons. In 124 cases booster doses of 10 x 2 Gy were administered. 22 patients were boosted after the breast irradiation with doses of 3 x 3,5 x 2,7 x 3 or 10 x 2 Gy. Because of the variation in fraction size, total doses were recalculated for analysis to biological equivalent doses of 2 Gy per fraction, assuming an a@ ratio of 10 Gy. Treatmentfree intervals during irradiation occurred in most schedules, except in the low-dose schedules (below 45 Gy in 5 weeks). In natipnrc treated I7 ,k: CI rl’ --..-I .__..-__ with .,.... .P nwhinntir Y--V.yY.-- flach . . . . . . \” f-k) -J/Y -3-7 dzyS usually passed between this flash and the start of radiation to the breast. In most patients an interval of 2-4 weeks was planned Table 2. Operable breast cancer treated with radiotherapy alone (UZCC staging)
Tis TO Tl T2 T3 Total
NO
Nl
Total
17* 1 28 91 27
0 1 2 33 21
17 2t 30 124 48
57
221
164
*2 patients had malignant nipple fluid, 1 ductular carcinoma in situ and 14 Paget’s disease. t2 patients had biopsy-proven invasive ductular carcinoma.
675
Table 3. Fractionation schedulesfor Tis-T3 breast cancer cases
Prebioptic flash
No. of fractions
Fraction size (~GY)
Total dose (GY)
No.
0
14-21
210-400
35.6-46.8
4
0
2 x 600
21-25 19-23
200-255 2OS2 10
52 -57.8 50.1-58.2
3 14
0 2 x 400 2 x 600
27-33 27 23-27
200-25s 200-210 20&300
60-69.9 62 63-66
11
2 x 400
23
205410
73.2
0 2 x 600
32-33 29-30
224-233 200-2 10
73.9-78.5 72-75
4 43
0 2 x 400 2 x 600
39-40 34 32-36
210-250 220-233 200-300
80.9-86.1 84.2 80.1-89.1
7 1 8
0 2 x 600
42-44 37-42
200-200 200-220
90.5-96.7 91.1-100.4
5 64
0 2 x 600 2 x 600
48 38-47 45-47
200-220 200-280 200-280
103.1 100.2-109.2 112.5-113.5
1 47 3
1 3 1
after 45-50 Gy. Another rest period of 2 days to 2 weeks occurred before the boost irradiation. In some of the patients, I.I”WC”CI) _..._..a.. +“_n+-__, +-..,a1111=1 :..*,..*,,,* ..,a..,,..,...X. ~,,-“,,C_ ,c ,.n+: ‘ Llr*llll~llL-IIcL YLLlJ WC&C l”115L’ “CCLLUJC “I pat’ents’ illness, temporary overload of the radiotherapy department, or due to an administrative mistake in the appointments of 1 patient. Total split-times were calculated for each patient by summing all the treatment interruption days. No patient received adjuvant hormonal therapy or chemotherapy. Analysis
Survival and local control rates have been calculated according to the actuarial life-table method. Significance of differences between subsets of patients was assessed by the log-rank test. Prognostic factors for local control were analysed with a stepwise, proportional hazards, general linear model. RESULTS Survival
Overall survival was 67.7% at 5 years, 39.7% at 10 years, 19.5% at 15 years and 6% at 20 years. Disease-free survival was 60.6%, 46.8% and 38% at 5, 10 and 15 years, respectively. Local recurrences
Local recurrences in the breast and/or on the thoracic wall (within the radiation field) occurred in 38 patients (17.2%). 22 recurrences were at the original tumour site, while in 2 patients the recurrence was located in another quadrant of the breast. The tumour recurred diffusely in the breast with involvement of the skin in 6 patients. In 7 patients the recurrence involved not only the treated breast but also the skin of the thoracic wall. In 1 patient, treated elsewhere for a breast recurrence, the exact location of the recurrent tumour cannot be specified. Thn n,.+*.nr;n1l”Cal I,\ml r-r*.r..~..m ..ntn nt nr.A 1F 111bacILLLIII(II IC~“IICII~CIllLL LaLcJ) 1n I” dl,U 1J .._“..C yra,> .*,nr WL13 17%, 19.1% and 24.6%, respectively. The annual risk for recurrence was 3.3% per year during the first 5 years, declining to 1% per year between the 5th and 14th year. After 14 years
pa1eaJl (%p) sase3 9~ 30 1no 1 Quo u! ase3 ayl seM sg QseaJq aq1 u! sa3uaJJnaaJ peq 63 09 ueqi ~amol sasop qirm paleaJ1 saw3 1~ s JO mo E *(IO*• = J) 1cf) SS ueqi Jaq%lq sasop ql!~ paleall s1uaged lie u! %~1 LlleniJ!A SAM~onuoa @JOI‘sJnouIni s!l-ol Jod *S alqel u! umoqs aJe asop uoye!peJ pue ale1s L 30 uoyun3 e se sa1eJ ioJ1uoa lea01 lepen1ae Jea6 S aqL *(que~ -it?01 ‘8I~'O = &lOJ,UOS [ea0130dq[!qeqoJd pUe paJalS+IIpe asopuope!pe~aqi uaawaq uogeiaJJo3 mea@@ e SBMaJaqL
.(p alqeL) (ys61eue a1e!JeA!ynur u! 610*0 = d pue aiepeaiun U! 90’0 = d) smaged JapIO JO3 Ueql (SJead 01 1e %9’18 ‘SA %8’S9) Op MOIaq pa%e siua!1ed 61 U! aSJOMSeM IOJlUOa @DOT aW ‘(fjE0’0 = J) smoum 11PW 1 apeJ8 JO3%9'58 gl!MpaJedLuoa %I’59 SeMSJead 01 leIOJlUOa lea01:smouml paq1uaJa33!p (111 aper OHA) QJood u! uaas aJaM sqnsaJ asJoM dpuex@~g wogepuaJa33rp 30 aaJ8ap aqi 01 pa1elaJ SBM ~0~1~03lea01‘ezuou!aJea lelnlanpJod *e!uoumaud 30 asnesaq hg op Ja13e (Jaqim3 aas) s6ep 811 30 leaJam! aaJ3 -1uaurleaJ1 e peq luaged S!ql ‘JaAaMOH ‘69 Z“ Q!M palean ‘Jnouml ZJ. e :aauaJJnsaJ ~301 e peq seq 1 Quo eurouplea lepqol .lOJlUOa leJO[JOJ aA!Sl?AU!ql~M s1uagedLI aq130 *eUIOU!aJeaJe~nqO~~l!M sluaped SJOlae3 a!lsou8oJd luequ8!s luapuadapu!aJaM (pElO'() = J) 30 Jaqumu ~pxus aql 01 anp iliq!ssod ‘(9~0.0 = J) meay*!s a%e pue (Zo()o*o = d) azts Jnotunl ‘(~o(yo= cl) skep ‘JaAaMOq‘IOUSeMaXIaJa33I$ aqL ‘(9 alqEL) (SJea6 S1 1e %(j’ZL SL Ueql JaiktOl IeAJalU! aJ3-lUaWeaJ1 ‘(81@)*0 = J) JnOUInl ‘Wead S 1e p.08) eUIOU!Xee:,Je~nlXIpaA!SeAU!ql!M smayd ayl 01 asop lelolaql ‘s!sdieue alepeapptu ayl UI *sasdleue E8l u!Ueql (SJEad SI It? %L’98 ‘SJeak Slr!%OOl)JelnqO~aA!SeA~ alepeapptu pue (p alqeL) aie!JeA!un u! ~onuoa lea01 uo lxdq gl!M siuayed sl u! palou aJaM saleJ ~0~1~03 @aoi JanaH J!aq1103 palsal aJaM awn-1gds [elol pue asop uo!ie~eJ se IlaM se snle1s @pou pur! az!s Jnoum1 ‘uoyepuaJa33!p3o aaJIbp ‘sadbqns ~ea@OlOls!q‘SnWlS @snedouatu ‘a8e se q3ns ‘SJOPE~sno!JeA *luauneaJl Jal3e sJead 0~ 01 dn (yspie s1uaged 1z) sJoA!AJnsaql u! saauaJJnaaJ ie~ol aJow ou aJaM aJayl .(z ?I!& dqdedouxtuetu uo Jaiaure!p Jnouml UIJ rad aleJ aJnlp3 Jeail 01 aq1 u! %g 30 aseaJau! ue 01 papuodsaJJos sg~ ‘(&o’o = J) sJead 01~03 dn paMo[[o3s1uaged3o %AU! paJJnaaJ kydeJ8ouxunxu uo ur3 5 ueq1 aJom %upnseaux smouxn~ xx3 s pue 1 *EuaaAuaq suo!sal30 %5*6z u! put! ‘ur3 E pue 1.1 uaaMlaq suo!sai 30 %LI u! Q,ua 1 ueyi Jalletus suo!sal 30 %p y uaas aJaM slead ()I leSaauaJJnaaJ lea07 .I ‘%g u! UMO~S aJe ‘s1uaF)ed 58 1 U! dydeJ8ounueur uo paJnseaur se ‘azls JnouJn130 uogaun3 e SE SaleJ lOJlUO3lEaO7 '(pa\qeL)SJOUInlEL JO3%l'OL pur! Z.LJo3%S'O8 ‘IL Jo3 %ti’98 ‘s!.L Jo3 %P6 ‘emou!aJI2a 01 W!M sluayed z u! %0()~ aJaM sJead 01 le SaleJ~0~1~0s lea01 @penlsv '1OJlUOa @301 vl!M pale~aJJO3 d~lUeaT.@$S aJaM ~~deJ8ouIun?m uo pamseaur az!s se IlaM se az!s @a!~!13 *loJiuoa @aor 30 61!1!qeqoJd pue az!s Jnoumi uaamlaq uoyelar e SBM aJayJ az?srnouty
*Lqdetiommew no pamseaw +s mowI 30 uopamr~ e se losuoa @a0130 .Qyqeqord
lead
01 *z *Sy
9 I
9 I
c I
f I
2 I
I I
~1uexgu~~rs 1ou = SN ys6Ieue alepenpn, 9’P9 E’S8
6’ZL L’98
9LO’O
I’S9 9’58
I’S9 8’LL
8fO’O
I ‘OL 5’08 P’98
Z’O9 I’PL P’98
LSEO’O
1’6L
SOO’O
90’0 I
O't?l
Z’PL t6
SN
(~3) az!s mounl L I
i7’9L 8’59
P’8L L’98 I ‘6L P6 9’18 8’59
S’ZL
9’98
LS
P91
ZP ZOI
SI’OL SE‘L8
8P PZI Of
I’OL P’S8 f’98
P’O8 001 I’Z8 P6 l’P8 8’59
1’08
P’SL
-
1’6L L’I8
8’ZL L’I8
LO’0
(%I 1.401
I’f8 L’18 I’f8 (%) Jh S
IN ON El Z.L II IIIQ IIE) + I3 vaI uon+=wa ~a3ue3Jepima
J~XJe3~A!Sk?AUI
POZ
Jawe3 Jelnqo?
f81 LI LI zoz
61
5
(%I Jd 51
rd
ZSI L9
S!~X.!SEAU!-UON OK
ot> (9 a&’ Iesnedouatu-lsod [esnedouauxald IIV
IZZ 'ON
mopI @uaylo~pv~ l#n pa1va.41.wxlv3 ova.4q ayqmado ylfm auayvd uf sam lomw3 pno1 p?.mni~y ‘p alqvl
677
Local Control of Operable Breast Cancer Table 5. Operable breast cancer-local
0277-5379190$3.00 + 0.00 0 1990PergamonPressplc
Local Control of Operable Breast Cancer after Radiotherapy Alone E. Van Limbergen, E. Van der Schueren, W. Van den Bogaert and J. Van Wing
221 patients with operable breast carcinoma stage Tis, Tl, T2, T3, NON1 were treated with radiotherapy alone without tumorectomy. The mean follow-up time was 15.5 years (range S-22). The annual risk for local recurrence was 3% during the first 5 years and 1% during the following 10 years, resulting in an actuarial local control rate of 75.4% after 15 years. The risk for local recurrence was assessed in multivariate analysis and was significantly related to the size of the tumour measured on mammography (P = 0.0002), the radiation dose administered (P = O.OOlS),the length of the split-course intervals being longer than 75 days (P= 0.001) and age (P= 0.019). Dose was related to response over a wide range as a function of tumour volume. All 18 patients with minimal tumour load (TO and Paget’s disease) treated with doses above SS Gy in 6 weeks achieved local control. S-year local control rates ranged from 40 to 100% for Tl carcinomas treated with 45-110 Gy, and from 0 to 95.3% for Tt carcinomas at the same dose. For T3 carcinomas local control varied between SOand 83% at 60-110 Gy. The risk for local failure increased by 8% per cm tumour diameter. With exclusive radiotherapy, the doses needed to provide local control rates similar to those obtained after tumorectomy and irradiation are 10 Gy higher for Tl (95% S year control) and 35 Gy higher for T2 (90% S year control). EurJ Cancer, Vol. 26, No. 6, pp. 674-679,1990.
INTRODUCTION Dr.7 .n”. ,.,.\YCrn.,r.lr. ^....- ,..... .Wllll ....t. ..,.rl:,rL,,,,.. I.,, l.,,,...,a DKutJI-L” nJCn”In~aulg;cly laulvulslapy lldL3 “FL”IIICa valid alternative to mastectomy in the treatment of operable stage I and II breast cancer [l-3]. Experience in operable breast cancer (UICC stages I, II, IIIA) treated with radiotherapy alone without tumorectomy is less extensive. In the early days of breast-conserving treatment radiotherapy alone was offered as an alternative to patients refusing mastectomy [4-61. These studies were extended into the megavoltage range, when mainly French institutions treated these patients with radiotherapy alone [7-91. High radiation doses are required for controi of breast cancer with radiotherapy alone [9-l 11. These high doses result in excessive fibrosis of normal tissues [12, 131. Therefore most centres now favour the combined treatment with surgery and radiotherapy for small breast tumors. Several groups [9, 11, 141 have shown that the possibility of breast cancer control with radiotherapy alone is related to tumour size and radiation dose. However, follow-up has been limited [9] or the dose range has been small. And the large study of Arriagada et al. [ 1l] mainly concerned patients with locally advanced rather than operable disease. We have updated the Leuven experience with more information on tumour size and dose response in patients with operable stage I, II and IIIA
breast cancer treated with radiotherapy alone. The follow-up of +l., ,..r:,..r, pG” . . . .luualy .. ..P.......IqJ” .._..__ +,& L7J TO,13 :, ll” ”_.., I,.., _.. *I..... UK panFur IICU W I” llgjFI L,,W,1 I,F .rsnm yralJ, while additional patients treated up to 1984 have been included. PATIENTS AND METHODS Patients
221 patients treated between 1967 and 1984 at the University Hospital of Leuven with radiotherapy alone for Tis, Tl, T2, T3, NON1 breast cancer have been analysed. Mean follow-up is 15.5 years (range 5-22). Most were treated before 1977 (94%). -_ __ Age ranges between 28 and 86 years (mean 5Y.4). Aii patients had undergone a Vim Silvermann needle biopsy and fine-needle aspiration cytology. The biopsy specimens and cytological slides were reviewed by J.V.W. The diagnosis of breast cancer was confirmed on biopsy in 195 cases and by cytology in 24 patients. In 2 patients both biopsy and cytological examination showed no breast cancer cells, but the clinical presentation, mammography and clinical course with metastases have confirmed the malignant character of the breast tumour. Biopsy samples were classified and graded according to the WHO classification (Table 1). All patients were reclassified according to 1987 UICC Tumouri Node/Metastases staging (Table 2). Tumour size was measured in 185 available mammograms. Radiation schedules 1967-1984 included
Correspondence to E. Van der Schueren, Department of Radiotherapy, Universitair Ziekenhuis, St RafaCl, B-3000 Leuven, Belgium. E. Van Limbergen, E. Van der Schueren, W. Van den Bogaert are at the Department of Radiotherapy and J. Van Wing is at the Department of Pathology, University Hospital, Leuven, Belgium.
the period of early experiences with breast-conserving therapy in Leuven. In the first patients treated, low radiation doses were used (below 50 Gy). Gradually, higher doses were administered, up to 96 Gy in 1976. Later,
674
Local Control of Operable Breast Cancer Table 1. Operable breast cancer treated with radiotherapy alone (WHO classification) Invasive Morbus Paget Ductular GI GII GIII Not graded Lobular Medullary Colloid Malignant nipple fluid No histological confirmation*
0 182 32 70 42 38 17 2 1
Total
204
Non-invasive 14 1
2 2 17
doses were lowered to 65 Gy. The doses have been recalculated for all patients and specified at midline depth on the central axis of the beam, as is recommended by the ICRU (International Commission on Radiation Units and Measurements) (Table 3). 185 patients received 2 X 6 Gy (n = 182) or 2 x 4 Gy (n = 3) with 13-15 MeV of a Brown Bovery Betatron on limited fields, as a ‘prebiopric flash’ before biopsy. Totai doses to the whoie breast range between’36 and 85 Gy. Most patients have received either about 40 Gy in 4 weeks (n = 33), 60-65 Gy in 8-10 weeks (n = 164), with fraction sizes ranging between 200 and 225 cGy per day. 15 patients have received higher total doses to the breast (up to 85 Gy). After the breast irradiation, booster doses on limited fields were administered to the primary tumour area in 146 patients, usually with 15 MeV electrons. In 124 cases booster doses of 10 x 2 Gy were administered. 22 patients were boosted after the breast irradiation with doses of 3 x 3,5 x 2,7 x 3 or 10 x 2 Gy. Because of the variation in fraction size, total doses were recalculated for analysis to biological equivalent doses of 2 Gy per fraction, assuming an a@ ratio of 10 Gy. Treatmentfree intervals during irradiation occurred in most schedules, except in the low-dose schedules (below 45 Gy in 5 weeks). In natipnrc treated I7 ,k: CI rl’ --..-I .__..-__ with .,.... .P nwhinntir Y--V.yY.-- flach . . . . . . \” f-k) -J/Y -3-7 dzyS usually passed between this flash and the start of radiation to the breast. In most patients an interval of 2-4 weeks was planned Table 2. Operable breast cancer treated with radiotherapy alone (UZCC staging)
Tis TO Tl T2 T3 Total
NO
Nl
Total
17* 1 28 91 27
0 1 2 33 21
17 2t 30 124 48
57
221
164
*2 patients had malignant nipple fluid, 1 ductular carcinoma in situ and 14 Paget’s disease. t2 patients had biopsy-proven invasive ductular carcinoma.
675
Table 3. Fractionation schedulesfor Tis-T3 breast cancer cases
Prebioptic flash
No. of fractions
Fraction size (~GY)
Total dose (GY)
No.
0
14-21
210-400
35.6-46.8
4
0
2 x 600
21-25 19-23
200-255 2OS2 10
52 -57.8 50.1-58.2
3 14
0 2 x 400 2 x 600
27-33 27 23-27
200-25s 200-210 20&300
60-69.9 62 63-66
11
2 x 400
23
205410
73.2
0 2 x 600
32-33 29-30
224-233 200-2 10
73.9-78.5 72-75
4 43
0 2 x 400 2 x 600
39-40 34 32-36
210-250 220-233 200-300
80.9-86.1 84.2 80.1-89.1
7 1 8
0 2 x 600
42-44 37-42
200-200 200-220
90.5-96.7 91.1-100.4
5 64
0 2 x 600 2 x 600
48 38-47 45-47
200-220 200-280 200-280
103.1 100.2-109.2 112.5-113.5
1 47 3
1 3 1
after 45-50 Gy. Another rest period of 2 days to 2 weeks occurred before the boost irradiation. In some of the patients, I.I”WC”CI) _..._..a.. +“_n+-__, +-..,a1111=1 :..*,..*,,,* ..,a..,,..,...X. ~,,-“,,C_ ,c ,.n+: ‘ Llr*llll~llL-IIcL YLLlJ WC&C l”115L’ “CCLLUJC “I pat’ents’ illness, temporary overload of the radiotherapy department, or due to an administrative mistake in the appointments of 1 patient. Total split-times were calculated for each patient by summing all the treatment interruption days. No patient received adjuvant hormonal therapy or chemotherapy. Analysis
Survival and local control rates have been calculated according to the actuarial life-table method. Significance of differences between subsets of patients was assessed by the log-rank test. Prognostic factors for local control were analysed with a stepwise, proportional hazards, general linear model. RESULTS Survival
Overall survival was 67.7% at 5 years, 39.7% at 10 years, 19.5% at 15 years and 6% at 20 years. Disease-free survival was 60.6%, 46.8% and 38% at 5, 10 and 15 years, respectively. Local recurrences
Local recurrences in the breast and/or on the thoracic wall (within the radiation field) occurred in 38 patients (17.2%). 22 recurrences were at the original tumour site, while in 2 patients the recurrence was located in another quadrant of the breast. The tumour recurred diffusely in the breast with involvement of the skin in 6 patients. In 7 patients the recurrence involved not only the treated breast but also the skin of the thoracic wall. In 1 patient, treated elsewhere for a breast recurrence, the exact location of the recurrent tumour cannot be specified. Thn n,.+*.nr;n1l”Cal I,\ml r-r*.r..~..m ..ntn nt nr.A 1F 111bacILLLIII(II IC~“IICII~CIllLL LaLcJ) 1n I” dl,U 1J .._“..C yra,> .*,nr WL13 17%, 19.1% and 24.6%, respectively. The annual risk for recurrence was 3.3% per year during the first 5 years, declining to 1% per year between the 5th and 14th year. After 14 years
pa1eaJl (%p) sase3 9~ 30 1no 1 Quo u! ase3 ayl seM sg QseaJq aq1 u! sa3uaJJnaaJ peq 63 09 ueqi ~amol sasop qirm paleaJ1 saw3 1~ s JO mo E *(IO*• = J) 1cf) SS ueqi Jaq%lq sasop ql!~ paleall s1uaged lie u! %~1 LlleniJ!A SAM~onuoa @JOI‘sJnouIni s!l-ol Jod *S alqel u! umoqs aJe asop uoye!peJ pue ale1s L 30 uoyun3 e se sa1eJ ioJ1uoa lea01 lepen1ae Jea6 S aqL *(que~ -it?01 ‘8I~'O = &lOJ,UOS [ea0130dq[!qeqoJd pUe paJalS+IIpe asopuope!pe~aqi uaawaq uogeiaJJo3 mea@@ e SBMaJaqL
.(p alqeL) (ys61eue a1e!JeA!ynur u! 610*0 = d pue aiepeaiun U! 90’0 = d) smaged JapIO JO3 Ueql (SJead 01 1e %9’18 ‘SA %8’S9) Op MOIaq pa%e siua!1ed 61 U! aSJOMSeM IOJlUOa @DOT aW ‘(fjE0’0 = J) smoum 11PW 1 apeJ8 JO3%9'58 gl!MpaJedLuoa %I’59 SeMSJead 01 leIOJlUOa lea01:smouml paq1uaJa33!p (111 aper OHA) QJood u! uaas aJaM sqnsaJ asJoM dpuex@~g wogepuaJa33rp 30 aaJ8ap aqi 01 pa1elaJ SBM ~0~1~03lea01‘ezuou!aJea lelnlanpJod *e!uoumaud 30 asnesaq hg op Ja13e (Jaqim3 aas) s6ep 811 30 leaJam! aaJ3 -1uaurleaJ1 e peq luaged S!ql ‘JaAaMOH ‘69 Z“ Q!M palean ‘Jnouml ZJ. e :aauaJJnsaJ ~301 e peq seq 1 Quo eurouplea lepqol .lOJlUOa leJO[JOJ aA!Sl?AU!ql~M s1uagedLI aq130 *eUIOU!aJeaJe~nqO~~l!M sluaped SJOlae3 a!lsou8oJd luequ8!s luapuadapu!aJaM (pElO'() = J) 30 Jaqumu ~pxus aql 01 anp iliq!ssod ‘(9~0.0 = J) meay*!s a%e pue (Zo()o*o = d) azts Jnotunl ‘(~o(yo= cl) skep ‘JaAaMOq‘IOUSeMaXIaJa33I$ aqL ‘(9 alqEL) (SJea6 S1 1e %(j’ZL SL Ueql JaiktOl IeAJalU! aJ3-lUaWeaJ1 ‘(81@)*0 = J) JnOUInl ‘Wead S 1e p.08) eUIOU!Xee:,Je~nlXIpaA!SeAU!ql!M smayd ayl 01 asop lelolaql ‘s!sdieue alepeapptu ayl UI *sasdleue E8l u!Ueql (SJEad SI It? %L’98 ‘SJeak Slr!%OOl)JelnqO~aA!SeA~ alepeapptu pue (p alqeL) aie!JeA!un u! ~onuoa lea01 uo lxdq gl!M siuayed sl u! palou aJaM saleJ ~0~1~03 @aoi JanaH J!aq1103 palsal aJaM awn-1gds [elol pue asop uo!ie~eJ se IlaM se snle1s @pou pur! az!s Jnoum1 ‘uoyepuaJa33!p3o aaJIbp ‘sadbqns ~ea@OlOls!q‘SnWlS @snedouatu ‘a8e se q3ns ‘SJOPE~sno!JeA *luauneaJl Jal3e sJead 0~ 01 dn (yspie s1uaged 1z) sJoA!AJnsaql u! saauaJJnaaJ ie~ol aJow ou aJaM aJayl .(z ?I!& dqdedouxtuetu uo Jaiaure!p Jnouml UIJ rad aleJ aJnlp3 Jeail 01 aq1 u! %g 30 aseaJau! ue 01 papuodsaJJos sg~ ‘(&o’o = J) sJead 01~03 dn paMo[[o3s1uaged3o %AU! paJJnaaJ kydeJ8ouxunxu uo ur3 5 ueq1 aJom %upnseaux smouxn~ xx3 s pue 1 *EuaaAuaq suo!sal30 %5*6z u! put! ‘ur3 E pue 1.1 uaaMlaq suo!sai 30 %LI u! Q,ua 1 ueyi Jalletus suo!sal 30 %p y uaas aJaM slead ()I leSaauaJJnaaJ lea07 .I ‘%g u! UMO~S aJe ‘s1uaF)ed 58 1 U! dydeJ8ounueur uo paJnseaur se ‘azls JnouJn130 uogaun3 e SE SaleJ lOJlUO3lEaO7 '(pa\qeL)SJOUInlEL JO3%l'OL pur! Z.LJo3%S'O8 ‘IL Jo3 %ti’98 ‘s!.L Jo3 %P6 ‘emou!aJI2a 01 W!M sluayed z u! %0()~ aJaM sJead 01 le SaleJ~0~1~0s lea01 @penlsv '1OJlUOa @301 vl!M pale~aJJO3 d~lUeaT.@$S aJaM ~~deJ8ouIun?m uo pamseaur az!s se IlaM se az!s @a!~!13 *loJiuoa @aor 30 61!1!qeqoJd pue az!s Jnoumi uaamlaq uoyelar e SBM aJayJ az?srnouty
*Lqdetiommew no pamseaw +s mowI 30 uopamr~ e se losuoa @a0130 .Qyqeqord
lead
01 *z *Sy
9 I
9 I
c I
f I
2 I
I I
~1uexgu~~rs 1ou = SN ys6Ieue alepenpn, 9’P9 E’S8
6’ZL L’98
9LO’O
I’S9 9’58
I’S9 8’LL
8fO’O
I ‘OL 5’08 P’98
Z’O9 I’PL P’98
LSEO’O
1’6L
SOO’O
90’0 I
O't?l
Z’PL t6
SN
(~3) az!s mounl L I
i7’9L 8’59
P’8L L’98 I ‘6L P6 9’18 8’59
S’ZL
9’98
LS
P91
ZP ZOI
SI’OL SE‘L8
8P PZI Of
I’OL P’S8 f’98
P’O8 001 I’Z8 P6 l’P8 8’59
1’08
P’SL
-
1’6L L’I8
8’ZL L’I8
LO’0
(%I 1.401
I’f8 L’18 I’f8 (%) Jh S
IN ON El Z.L II IIIQ IIE) + I3 vaI uon+=wa ~a3ue3Jepima
J~XJe3~A!Sk?AUI
POZ
Jawe3 Jelnqo?
f81 LI LI zoz
61
5
(%I Jd 51
rd
ZSI L9
S!~X.!SEAU!-UON OK
ot> (9 a&’ Iesnedouatu-lsod [esnedouauxald IIV
IZZ 'ON
mopI @uaylo~pv~ l#n pa1va.41.wxlv3 ova.4q ayqmado ylfm auayvd uf sam lomw3 pno1 p?.mni~y ‘p alqvl
677
Local Control of Operable Breast Cancer Table 5. Operable breast cancer-local
