- Email: [email protected]
Sentinel node detection and radioguided occult lesion localization in breast cancer
2004 Workshop on the Nuclear Radiology of Breast Cancer Rome (Italy) October 22-23, 2004
,Physica Medica, 9 Vol. XXI, Supplement 1, 2006
Sentinel Node Detection and Radioguided Occult Lesion Localization in Breast Cancer Giuseppe Trifir6, Laura Lavinia Travaini, Concetta De Cicco, Giovanni Paganelli Division of Nuclear Medicine, European Institute of Oncology, Milan (Italy)
Abstract Sentinel lymph node biopsy might replace complete axillary dissection for staging of the axilla in clinically NO breast cancer patients and represent a significant advantage as a minimally invasive procedure, considering that about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidit)a. In our Institute, Radioguided Occult Lesion Localization is the standard method to locate non-palpable breast lesions and the gamma probe is very effective in assisting intra-operative localization and removal, as in sentinel node biopsy. The rapid spread of sentinel lymph node biopsy has led to its use in clinical settings previously considered contraindications to sentinel lymph node biopsy. In this contest, we evaluated in a large group of patients possible factors affecting sentinel node detection and the reliability of sentinel lymph node biopsy carried out after large excisional breast biopsy. Our data confirm that a previous breast surgery does not prohibit efficient sentinel lymph node localization and sentinel lymph node biopsy can correctly stage the axilla in these patients. KEYWORDS: Breast cancer, sentinel lymph node, lymphoscintigraphy, ROLL. 1. INTRODUCTION
Sentinel lymph node (SLN) localization and biopsy (SLNB) represents one of the most important developments in surgery and has already produced important changes in the management of patients (pts) affected by early infiltrating breast carcinoma. In the proceedings of the Consensus Conference (Philadelphia, 2001) on the role of SLNB in carcinoma of the breast, the panel considered SLNB to be a suitable replacement for axillary lymph node dissection (ALND) in carcinoma with a diameter below 3 cm and no clinically suspicious palpable axillary nodes [1]. Several technical aspects of lymphoscintigraphy (LS) have been optimised by our group, based on detailed investigations [2, 3, 4, 5]. In institutions where a high number of procedures are performed, the success rate of radioguidance in localizing the SLN in breast cancer surgery is about 97% and the success rate of LS in sentinel node detection is about 100%. In case of non-palpable lesions we use the technique named ROLL, acronym of Radioguided Occult Lesion Localization, and apply it to an ever increasing number of patients [6, 7, 8]. Following the mammographic or ultrasonic identification of a suspicious breast lesion, typically as a cluster of microcalcifications, opaque spot or parenchymal distortion, use of ROLL facilitates the diagnostic process in order to obtain the precise preoperative localization of the lesion and its complete removal with a sufficient margin of healthy tissue. The rapid spread of SLNB has led to its use in clinical settings previously considered contraindications to SLNB. In this contest, we have evaluated possible factors affecting sentinel node detection and the reliability of SLNB carried out in special
conditions, i.e., pregnancy or after large excisional breast biopsy. Some authors have suggested that altered lymphatic drainage decreases the likelihood of successful lymphatic mapping and, indeed, that SLNB for breast cancer may be less accurate after excisional biopsy of the primary tumour [9, 10, 11]. Other authors [12, 13] claim that neither biopsy type nor type of definitive surgical procedure significantly affects the accuracy of SLNB for breast cancer, and that SLNB can be performed accurately after excisional biopsy and is equally effective in patients undergoing partial mastectomy or total mastectomy, 2. MATERIAL AND METHODS
From January 1998 to December 2003 we enrolled five-hundred-twenty-two (522) selected patients (pts) with breast carcinoma diagnosed by histological examination through large excisional biopsy or quadrantectomy, All pts were submitted to lymphoscintigraphy for SLNB; pts with previous excisional biopsy were also scheduled for surgical radicalization of the tumour. Patients with multicentric breast cancer or previously submitted just to incisional biopsy, fine-needle aspiration or vacuum assisted core biopsy (Mammotome) were excluded. Informed consent was obtained from all pts. Radiopharmaceuticals were injected in the Nuclear Medicine Department as a single aliquot of 12-15 MBq of 99mWclabelled nanocolloids (particle size < 80 nm) of human serum albumin (Nanocoll, Amersham Health, Milan, Italy) in 0.2 ml of volume, using a 25-gauge needle, intraparenchymally in the previous biopsy cavity or subdermally, close to the scar.
Address for correspondence: Giovanni Paganelli: Phone: + 39 02 57489043; Fax: + 39 02 57489040. E-mail: [email protected] 2. Nuclear Medicine Perspective
<
After the radiocolloid injection, the areawas massaged gently (or a hot support was laid on the area) for a short time (2-3 minutes) without yielding discomfort and improving the lymphatic drainage. Static im~tges in anterior and oblique anterior views were obtained, collecting 150 Kcounts. The energy setting ,)1~the gamma-camera was on the 140 KeV emissio i peak of 99mWcwith a ___20% window, highresoluti.)n collimator, z o o m 1, acquisition matrix 128 • 12 ~;pixels. A furtt~ er administration of 12 MBq 99mZclabelled nanocoll:fids of h u m a n serum albumin in 0.2 ml of volurae, using a 25-gauge needle, was injected subdermally, close to the scar, if SLN was not identified 16 hours after the first intraparenchymal injection. An indelible marker was placed on the skin projection o1: the SLN and its location confirmed by using a hand-held-probe (Neo 2000 gds, Neoprobe Corp., Dublin, Ohio, US; MR 100, Pol. hi. tech. L'Aquila Italy). All pts underwent SLNB, completed with ALND in case of metastatic SLN. The ,';ZNB was performed using an intra-operative g a m n a probe detection; all hot axillary lymph nodes w:'.re considered as SLNs and separately sent for histological evaluation. SLNs located outside the axilla x~ere not removed. Analy,~ is of average age of patients and time between r]~:st surgical intervention and lymphoscintigraphic study was performed in the two groups (intraparenchymal and subdermal) with the t test. 3. RESU,TS A total of 522 pts (517 female, 5 male) were enrolled in this study. Characteristics of patients are listed in Table 1. The radiotracer administration was performed subdermally in 328/522 (62.8%) and intraparenchymally in the remaining 194 pts (37.2%). The differeece in size of the two groups is due to our preference in performing only the subdermal injection after a first period in which the two types of administration were equally carried out. In the subdermal group LS was able to identify SLNs in all pts. By contrast, the rate of SLN identification in the intraparenchymal group was 78% (152/194). In 42 pts a second subdermal injection was needed, which was successful in 34 cases. Overall LS localized almost one SLN in 514/522 pts (98.5%); the mean n u m b e r of axillary SLNs identified was 1.3 ___0.7 (range 1-5). In 491 pts (95.5%) the radiotracer drained to the homolateral axilla only; in 23 pts (4.5%) we obserw.'d also a drainage outside the axilla (internal mar:lmary chain, clavicular or i n t r a m a m m a r y lymph nodes). In 486 pts surgical radicalisation of the primary turnout was performed.
Histology of the primary lesions showed 377 (72.2%) infiltrating ductal carcinomas (IDC), 61 (11.7%) infiltrating lobular carcinomas (ILC), 16 mixed (3.0%) and 68 others (13.1%). SLNB was performed in 5 1 4 / 5 2 2 pts (98.5%): 382 (74.3%) pts received SLNB only while in 132 pts (25.7%) SLNB was completed by ALND. In 87/132 (65.9%) the SLN was the only lymph node involved; in the remaining 45/132 (34.1%) other axillary lymph nodes were involved. In 8 pts the surgeon carried out the ALND directly, since no SLN were identified at LS. We did not observe any statistically significant difference in the average age and time between first surgical intervention and LS in the two groups (intraparenchymal and subdermal), with a median interval of forty-three days. Pathological findings are summarised in Tables 2 and 3. 4. DISCUSSION
Dermal and parenchymal lymphatics of the breast drain to the same axillary nodes in most patients with a high level of concordance [14, 15]. The SLN concept is based on the orderly progression of tum o u r cells within the lymphatic system [16] and LS is able to determine the n u m b e r of lymph nodes that are on a direct drainage pathway and to locate them. It has been demonstrated that the intraderm a l / s u b d e r m a l injection is associated with a high rate of lymph nodes visualisation, mainly located in the axilla which is correctly staged by SLNB. Some problems arise in the m a n a g e m e n t of patients submitted to diagnostic excisional breast biopsy due to the avsence of axillry lymp nodes staging. Usually, patients already submitted to breast biopsy have not been enrolled in lymphoscintigraphic studies for SLN detection because lymphatic disruption or presence of granulation, inflammatory tissue and h a e m a t o m a are suppose to alter the original lymph drainage leading to SLN detection failure or false negative results [17, 18, 19].
TABLE 1. Patients" characteristics. Age
median range Pathology invasive ductal carcinoma invasive lobular carcinoma mixed others Days between biopsy and LS median range Previous surgery excisional biopsy quadrantectomy
49.8 23-84 377
61 16 68 43 4-295
486 (93.1%) 36 (6.9%) 21
Giuseppe Trifir6 et alii: Sentinel Node Detection and Radioguided Occult Lesion Localization in Breast Cancer TABLE2. Pathological characteristics of SLN and axillary lymph nodes in 132 pts with metastatic involvement. SLSB
Axillary lymph nodes status negative
Mts* Micromts** Total
83 49 132
41 44 85
micromts
1-3 LN o mts
> 3 LN ~ mts
1 2 3
22 3 25
19 0 19
* mts = metastases;** micromts = micrometastases; ~
TABLE3. Pathological characteristics of SLNB and pT. Primary tumour
SLNB+
Tla Tlb Tlc T2
17 (16.1%) 24 (18.5%) 59 (31.2%) 32 (35.9%)
SLNB 89 (83.9%) 106 (81.5%) 130 (68.8%) 57 (64.1%)
Total 106 130 189 89
However, possible advantages of minimally invasive surgical approach must be considered also in patients with breast cancer provided by excisional biopsy in which an axillary dissection often represents an over treatment in relation to the small dimension of the primary lesion. Indeed, while the role of LS and SLNB is a well accepted m e t h o d to stage regional lymph nodes in m e l a n o m a patients undergone biopsy or wide local excision [20], the procedure is still an open question in subjects with prior breast biopsy. Krag [21] reported a higher frequency of failure in identifying SLN in patients with prior surgical biopsy when compared with patients who did not, assuming that a prior biopsy cavity reduced the probability of finding the SLN; also Borgstein [9] noted significantly lower likelihood of successful SLNB in patients w h o had a previous excision biopsy Both Krag and Borgstein, in spite of different radiotracers administered, used in their studies large volume of radiocolloids (4 ml) which may affect SLNB identification independently on the presence of scar. On the contrary Haigh et alii [22] reported a success rate in SLN identification of 83.4% in patients submitted to excisional biopsy using blue dye alone and their study , d o c u m e n t s successful SLND for patients who have had large excisions before SLND or immediate or delayed slnd from biopsy~. Miner et alii [13], in a study of 82 patients, affirmed that the type of prior biopsy had no significant effect on ability to localize the sln with a high percentage of successful sln detection (98%), in spite of large volume of 99m-tecnetium-sulfur colloid administrated. More recently, in a study with a large series of patients, Wong et alii [12] demonstrated that SLN localisation and SLNB is highly successful in breast cancer patients regardless of biopsy method, excision volume, and the interval between the biopsy and the SLN procedure. The authors also found that the dermal injection is a m e t h o d more reliable and accurate than the peritumoral and that 22
= lymph node
difference in SLNB success rate may depend on various injection techniques more than disruption of lymphatic vessels or inflammatory changes. With the present trial we decided to evaluate only patients previously submitted to large excisional biopsy or quadrantectomy in relation to the larger tissue volume removed, excluding procedures as fine-needle aspiration, incisional or core biopsy where a major disruption of lymphatic pathways is unlikely to occur. In case of palpable residual disease, we carried out lymphoscintigraphy according to our standard procedure whereas in presence of non-palpable lesion we performed roll associated to a subdermal radiotracer administration [8]. The results obtained in this series of patients demonstrated that lymphoscintigraphy has a high rate of success (98.5%) also w h e n carried out in presence of scar and that subdermal route of injection shows to be superior to the intraparenchymal one, with a SLN visualisation in all patients. As regards the detection rate of the SLN, the results of the present study are not dissimilar from our already published data [24] and confirm that d e r m a l / s u b d e r m a l injection is a more effective route of administration rather than intraparenchymal one. In our opinion this technique may easily overcome the limitations in SLN detection reported by Wong [12] with the peritumoral administration. In relation to the extent of the removed breast tissue neither in patients with excisional biopsy (486 pts) nor in patients with previous quadrantectomy (36 pts) we found a significant difference in the SLN detection related to the elapsed time from breast biopsy, LS and pathological results. We normally avoid to perform a traditional intraoperative examination of the SLNS, whereby only 1 to 3 frozen sections are examined, and the rest of the node is left for the subsequent examination of p e r m a n e n t sections. In this event, a high rate of false-negative intraoperative diagnoses is necessarily expected, with the need for a second operation to complete axillary lymph node dissection in almost 17% of the patients. The above extensive pathological examination of the SLN has been designed to identify in the SLNS even micrometastatic disease (i.e. t u m o u r foci up to 2 m m in size) which can escape detection by less accurate evaluation. A limitation of the present study is that only patients with metastatic SLN received
<
Ell]
ACKNOWLEDGEMENTS
[13]
W o r k su] ~ported b y g r a n t s o f t h e Italian A s s o c i a t i o n for C a n c e r R e s e a r c h (AIRC). T h e a u t h o r s t h a n k Dr. D a r i n e G h a n e m for h e r k i n d as,,i!:tance in revising t h e English o f this m a n u script.
[14]
REFEREb CES
[15]
Schwartz G F, Giuliano A E, Veronesi U. Consensus Ccr ference Committee. Proceedings of the consensus co~a!erence on the role of sentinel lymph node biopsy in cm'c noma of the breast, April 19-22,2001, Philadelphia (PE:. Cancer 2002:15 (94); 2542-2551. [2] D( 2icco C, Cremonesi M, Luini A, Bartolomei M, Gialla C, Prisco G, Galimberti V, Calza P, Viale G, Ver,,nesi U, Paganelli G. Lymphoscintigraphy and radi~~F.uided biopsy of the sentinel axillary node in breast ca:~ er. J Nucl Med 1998: 39; 2080-2084. [3] Paganelli G, Galimberti V, Trifir6 G, Travaini L, De Ci:,:o C, Mazzarol G, Intra M, Rocca R Prisco G, Veto1 :si U. Internal mammary node lymphoscintigraphy anJ biopsy in breast cancer. Q J Nucl Med 2002: 46; 13 g 144. [4] De: ',2icco C, Baio S M, Veronesi R Trifir6 G, Ciprian A, Pr s,:o G, Vento A, Rososchansky J, Viale G, Paganelli G. !;entinel node biopsy in male breast cancer. Nucl M,>:. Commun 2004:25 (2); 139-143. [5] [51 .uini A, Gatti G, Frasson A, Naninato R Magalotti C, L~rnone P, Viale G, Pruneri G, Galimberti V, De Cicco C, Veronesi U. Sentinel lymph node biopsy performed witL local anesthesia in patients with early-stage breast ca :cinoma. Arch Surg 2002: 137; 1157-1160. [6] Dc Cicco C, Pizzamiglio M, Trifir6 G, Luini A, Ferrari M 13risco G, Galimberti V, Cassano E, Viale G, Intra M Veronesi R Paganelli G. Radioguided occult lesion loc~ lisation (roll) and surgical biopsy in breast cancer. Technical aspects. Q J Nucl Med 2002 Jun: 46 (2); 145151 [7] Paganelli G, Luini A, Veronesi U. Radioguided occult lesi, ,n localization (ROLL) in breast cancer: maximizing efli~:acy, minimizing mutilation. Ann Oncol 2002 Dec: 13 (12); 1839-1840. [8] De Cicco C, Trifir6 G, Intra M, Marotta G, Ciprian A, Frasson A, Prisco G, Luini A, Viale G, Paganelli G. Optimised nuclear medicine method for tumour marking and sentinel node detection in occult primary breast lesions. Eur J Nucl Med Mol Imaging. 2004 Mar: 31; 349-354. [9] Borgstein P J, pijpers R, Comans E F et alii. Sentinel lymph node biopsy in breast cancer: guidelines and pitfidls of lymphoscintigraphy and gamma probe detection. J Am Coll Surg 1998: 186; 275-283. [10] Mc,dasters K M, Giuliano A E, Ross M I, Reintgen D S, H,~:lt K K, Byrd D R, Klimberg V S, Whitworth P W,, T~fla L C, Edwards M J. Sentinel-lymph-node biopsy foe ~reast cancer-not yet the standard of care. N Engl J Id ed 1998: 339; 990-995.
[12]
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[23]
[24]
Ollila D W, Giuliano A E. Intraoperative lymphatic mapping and sentinel lymphadenectomy using isosulfan blue dye. Breast Dis 1998: 8; 297-300. Wong S L, Edwards M J, Chao C, Tuttle T M, Noyes R D, Carlson D J, Laidley A L, McGlothin T Q, Ley P B, Brown C M, Glaser R L, Pennington R E, Turk P S, Simpson D, McMasters K M. The effect of prior breast biopsy method and concurrent definitive breast procedure on success and accuracy of sentinel lymph node biopsy. Ann Surg Oncol 2002: 9; 272-277. Miner T J, Shriver C D, Jaques D P, Maniscalco-Theberge M E, Krag D N. Sentinel lymph node biopsy for breast cancer: the role of previous biopsy on patients eligibility. Am Surg 1999: 65; 493-499. Boolbol S K, Fey J V, Borgen P I, Heerdt A S, Montgomery L L, Paglia M, PetrekJ A, Cody H S 3rd, Van Zee KJ. Intradermal isotope injection: a highly accurate method of lymphatic mapping in breast carcinoma. Ann Surg Oncol 2001: 8; 20-24. Mateos J J, Vidal-Sicart S, Zanon G, Pahisa J, Fuster D, Martin F, Ortega M, Fernandez P, Pons E Sentinel lymph node biopsy in breast cancer patients: subdermal versus peritumoral radiocolloid injection. Nucl Med Commun 2001: 22; 17-24. Reintgen D, Cruse C W, Wells K, Berman C, Fenske N, Glass F, Schroer K, Heller R, Ross M, Lyman G e t alii. The orderly progression of melanoma nodal metastases. Ann Surg 1994: 22; 759-767. Veronesi U, Paganelli G, Galimberti V, Viale G, Zurrida S, Bedoni M, Costa A, de Cicco C, Geraghty JG, Luini A, Sacchini V, Veronesi P. Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes. Lancet 1997: 349; 1864-1867. Feldman S M, Krag D N, McNally R K, Moor B B, Weaver D L, Klein P. Limitation of gamma probe localization of the sentinel node in breast cancer patients with large excisional biopsy. J Am Coll Surg 1999:188; 248-254. Kumar R, Jana S, Heiba S I, Dakhel M, Axelrod D, Siegel B, Bernik S, Mills C, Wallack M, Abdel-Dayem H M. Retrospective analysis of sentinel node localization in multifocal, multicentric, palpable, or nonpalpable breast cancer. J Nucl Med 2003: 44; 7-10. Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V, Intra M, Veronesi P, Robertson C, Maisonneuve P, Renne G, De Cicco C, De Lucia F, Gennari R. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 2003: 349; 546-553. Krag D, Weaver D, Ashikaga T, Moffat F, Klimberg V S, Shriver C, Feldman S, Kusminsky R, Gadd M, Kuhn J, Harlow S, Beitsch P. The sentinel node in breast cancer-a multicenter validation study. N Engl J Med 1998: 339; 941-946. Haigh P I, Ansen M N, Qi K, Giuliano A E. Biopsy method and excision volume do not affect success rate of subsequent sentinel lymph node dissection in breast cancer. Ann Surg Oncol 2000: 7; 21-27. Maza S, Valencia R, Geworski L, Zander A, Guski H, Winzer KJ, Munz DL. Peritumoral versus subareolar administration of technetium-99m nanocolloid for sentinel lymph node detection in breast cancer: preliminary results of a prospective intra-individual comparative study. Eur J Nucl Med Mol Imaging 2003 May: 30 (5); 651-656. De Cicco C, Cremonesi M, Luini A, Bartolomei M, Grana C, Prisco G, Galimberti V, Calza P, Viale G, Veronesi U, Paganelli G. Lymphoscintigraphy and radioguided biopsy of the sentinel axillary node in breast cancer. J Nucl Med 1998: 39; 2080-2084.
23
,Physica Medica, 9 Vol. XXI, Supplement 1, 2006
Sentinel Node Detection and Radioguided Occult Lesion Localization in Breast Cancer Giuseppe Trifir6, Laura Lavinia Travaini, Concetta De Cicco, Giovanni Paganelli Division of Nuclear Medicine, European Institute of Oncology, Milan (Italy)
Abstract Sentinel lymph node biopsy might replace complete axillary dissection for staging of the axilla in clinically NO breast cancer patients and represent a significant advantage as a minimally invasive procedure, considering that about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidit)a. In our Institute, Radioguided Occult Lesion Localization is the standard method to locate non-palpable breast lesions and the gamma probe is very effective in assisting intra-operative localization and removal, as in sentinel node biopsy. The rapid spread of sentinel lymph node biopsy has led to its use in clinical settings previously considered contraindications to sentinel lymph node biopsy. In this contest, we evaluated in a large group of patients possible factors affecting sentinel node detection and the reliability of sentinel lymph node biopsy carried out after large excisional breast biopsy. Our data confirm that a previous breast surgery does not prohibit efficient sentinel lymph node localization and sentinel lymph node biopsy can correctly stage the axilla in these patients. KEYWORDS: Breast cancer, sentinel lymph node, lymphoscintigraphy, ROLL. 1. INTRODUCTION
Sentinel lymph node (SLN) localization and biopsy (SLNB) represents one of the most important developments in surgery and has already produced important changes in the management of patients (pts) affected by early infiltrating breast carcinoma. In the proceedings of the Consensus Conference (Philadelphia, 2001) on the role of SLNB in carcinoma of the breast, the panel considered SLNB to be a suitable replacement for axillary lymph node dissection (ALND) in carcinoma with a diameter below 3 cm and no clinically suspicious palpable axillary nodes [1]. Several technical aspects of lymphoscintigraphy (LS) have been optimised by our group, based on detailed investigations [2, 3, 4, 5]. In institutions where a high number of procedures are performed, the success rate of radioguidance in localizing the SLN in breast cancer surgery is about 97% and the success rate of LS in sentinel node detection is about 100%. In case of non-palpable lesions we use the technique named ROLL, acronym of Radioguided Occult Lesion Localization, and apply it to an ever increasing number of patients [6, 7, 8]. Following the mammographic or ultrasonic identification of a suspicious breast lesion, typically as a cluster of microcalcifications, opaque spot or parenchymal distortion, use of ROLL facilitates the diagnostic process in order to obtain the precise preoperative localization of the lesion and its complete removal with a sufficient margin of healthy tissue. The rapid spread of SLNB has led to its use in clinical settings previously considered contraindications to SLNB. In this contest, we have evaluated possible factors affecting sentinel node detection and the reliability of SLNB carried out in special
conditions, i.e., pregnancy or after large excisional breast biopsy. Some authors have suggested that altered lymphatic drainage decreases the likelihood of successful lymphatic mapping and, indeed, that SLNB for breast cancer may be less accurate after excisional biopsy of the primary tumour [9, 10, 11]. Other authors [12, 13] claim that neither biopsy type nor type of definitive surgical procedure significantly affects the accuracy of SLNB for breast cancer, and that SLNB can be performed accurately after excisional biopsy and is equally effective in patients undergoing partial mastectomy or total mastectomy, 2. MATERIAL AND METHODS
From January 1998 to December 2003 we enrolled five-hundred-twenty-two (522) selected patients (pts) with breast carcinoma diagnosed by histological examination through large excisional biopsy or quadrantectomy, All pts were submitted to lymphoscintigraphy for SLNB; pts with previous excisional biopsy were also scheduled for surgical radicalization of the tumour. Patients with multicentric breast cancer or previously submitted just to incisional biopsy, fine-needle aspiration or vacuum assisted core biopsy (Mammotome) were excluded. Informed consent was obtained from all pts. Radiopharmaceuticals were injected in the Nuclear Medicine Department as a single aliquot of 12-15 MBq of 99mWclabelled nanocolloids (particle size < 80 nm) of human serum albumin (Nanocoll, Amersham Health, Milan, Italy) in 0.2 ml of volume, using a 25-gauge needle, intraparenchymally in the previous biopsy cavity or subdermally, close to the scar.
Address for correspondence: Giovanni Paganelli: Phone: + 39 02 57489043; Fax: + 39 02 57489040. E-mail: [email protected] 2. Nuclear Medicine Perspective
<
After the radiocolloid injection, the areawas massaged gently (or a hot support was laid on the area) for a short time (2-3 minutes) without yielding discomfort and improving the lymphatic drainage. Static im~tges in anterior and oblique anterior views were obtained, collecting 150 Kcounts. The energy setting ,)1~the gamma-camera was on the 140 KeV emissio i peak of 99mWcwith a ___20% window, highresoluti.)n collimator, z o o m 1, acquisition matrix 128 • 12 ~;pixels. A furtt~ er administration of 12 MBq 99mZclabelled nanocoll:fids of h u m a n serum albumin in 0.2 ml of volurae, using a 25-gauge needle, was injected subdermally, close to the scar, if SLN was not identified 16 hours after the first intraparenchymal injection. An indelible marker was placed on the skin projection o1: the SLN and its location confirmed by using a hand-held-probe (Neo 2000 gds, Neoprobe Corp., Dublin, Ohio, US; MR 100, Pol. hi. tech. L'Aquila Italy). All pts underwent SLNB, completed with ALND in case of metastatic SLN. The ,';ZNB was performed using an intra-operative g a m n a probe detection; all hot axillary lymph nodes w:'.re considered as SLNs and separately sent for histological evaluation. SLNs located outside the axilla x~ere not removed. Analy,~ is of average age of patients and time between r]~:st surgical intervention and lymphoscintigraphic study was performed in the two groups (intraparenchymal and subdermal) with the t test. 3. RESU,TS A total of 522 pts (517 female, 5 male) were enrolled in this study. Characteristics of patients are listed in Table 1. The radiotracer administration was performed subdermally in 328/522 (62.8%) and intraparenchymally in the remaining 194 pts (37.2%). The differeece in size of the two groups is due to our preference in performing only the subdermal injection after a first period in which the two types of administration were equally carried out. In the subdermal group LS was able to identify SLNs in all pts. By contrast, the rate of SLN identification in the intraparenchymal group was 78% (152/194). In 42 pts a second subdermal injection was needed, which was successful in 34 cases. Overall LS localized almost one SLN in 514/522 pts (98.5%); the mean n u m b e r of axillary SLNs identified was 1.3 ___0.7 (range 1-5). In 491 pts (95.5%) the radiotracer drained to the homolateral axilla only; in 23 pts (4.5%) we obserw.'d also a drainage outside the axilla (internal mar:lmary chain, clavicular or i n t r a m a m m a r y lymph nodes). In 486 pts surgical radicalisation of the primary turnout was performed.
Histology of the primary lesions showed 377 (72.2%) infiltrating ductal carcinomas (IDC), 61 (11.7%) infiltrating lobular carcinomas (ILC), 16 mixed (3.0%) and 68 others (13.1%). SLNB was performed in 5 1 4 / 5 2 2 pts (98.5%): 382 (74.3%) pts received SLNB only while in 132 pts (25.7%) SLNB was completed by ALND. In 87/132 (65.9%) the SLN was the only lymph node involved; in the remaining 45/132 (34.1%) other axillary lymph nodes were involved. In 8 pts the surgeon carried out the ALND directly, since no SLN were identified at LS. We did not observe any statistically significant difference in the average age and time between first surgical intervention and LS in the two groups (intraparenchymal and subdermal), with a median interval of forty-three days. Pathological findings are summarised in Tables 2 and 3. 4. DISCUSSION
Dermal and parenchymal lymphatics of the breast drain to the same axillary nodes in most patients with a high level of concordance [14, 15]. The SLN concept is based on the orderly progression of tum o u r cells within the lymphatic system [16] and LS is able to determine the n u m b e r of lymph nodes that are on a direct drainage pathway and to locate them. It has been demonstrated that the intraderm a l / s u b d e r m a l injection is associated with a high rate of lymph nodes visualisation, mainly located in the axilla which is correctly staged by SLNB. Some problems arise in the m a n a g e m e n t of patients submitted to diagnostic excisional breast biopsy due to the avsence of axillry lymp nodes staging. Usually, patients already submitted to breast biopsy have not been enrolled in lymphoscintigraphic studies for SLN detection because lymphatic disruption or presence of granulation, inflammatory tissue and h a e m a t o m a are suppose to alter the original lymph drainage leading to SLN detection failure or false negative results [17, 18, 19].
TABLE 1. Patients" characteristics. Age
median range Pathology invasive ductal carcinoma invasive lobular carcinoma mixed others Days between biopsy and LS median range Previous surgery excisional biopsy quadrantectomy
49.8 23-84 377
61 16 68 43 4-295
486 (93.1%) 36 (6.9%) 21
Giuseppe Trifir6 et alii: Sentinel Node Detection and Radioguided Occult Lesion Localization in Breast Cancer TABLE2. Pathological characteristics of SLN and axillary lymph nodes in 132 pts with metastatic involvement. SLSB
Axillary lymph nodes status negative
Mts* Micromts** Total
83 49 132
41 44 85
micromts
1-3 LN o mts
> 3 LN ~ mts
1 2 3
22 3 25
19 0 19
* mts = metastases;** micromts = micrometastases; ~
TABLE3. Pathological characteristics of SLNB and pT. Primary tumour
SLNB+
Tla Tlb Tlc T2
17 (16.1%) 24 (18.5%) 59 (31.2%) 32 (35.9%)
SLNB 89 (83.9%) 106 (81.5%) 130 (68.8%) 57 (64.1%)
Total 106 130 189 89
However, possible advantages of minimally invasive surgical approach must be considered also in patients with breast cancer provided by excisional biopsy in which an axillary dissection often represents an over treatment in relation to the small dimension of the primary lesion. Indeed, while the role of LS and SLNB is a well accepted m e t h o d to stage regional lymph nodes in m e l a n o m a patients undergone biopsy or wide local excision [20], the procedure is still an open question in subjects with prior breast biopsy. Krag [21] reported a higher frequency of failure in identifying SLN in patients with prior surgical biopsy when compared with patients who did not, assuming that a prior biopsy cavity reduced the probability of finding the SLN; also Borgstein [9] noted significantly lower likelihood of successful SLNB in patients w h o had a previous excision biopsy Both Krag and Borgstein, in spite of different radiotracers administered, used in their studies large volume of radiocolloids (4 ml) which may affect SLNB identification independently on the presence of scar. On the contrary Haigh et alii [22] reported a success rate in SLN identification of 83.4% in patients submitted to excisional biopsy using blue dye alone and their study , d o c u m e n t s successful SLND for patients who have had large excisions before SLND or immediate or delayed slnd from biopsy~. Miner et alii [13], in a study of 82 patients, affirmed that the type of prior biopsy had no significant effect on ability to localize the sln with a high percentage of successful sln detection (98%), in spite of large volume of 99m-tecnetium-sulfur colloid administrated. More recently, in a study with a large series of patients, Wong et alii [12] demonstrated that SLN localisation and SLNB is highly successful in breast cancer patients regardless of biopsy method, excision volume, and the interval between the biopsy and the SLN procedure. The authors also found that the dermal injection is a m e t h o d more reliable and accurate than the peritumoral and that 22
= lymph node
difference in SLNB success rate may depend on various injection techniques more than disruption of lymphatic vessels or inflammatory changes. With the present trial we decided to evaluate only patients previously submitted to large excisional biopsy or quadrantectomy in relation to the larger tissue volume removed, excluding procedures as fine-needle aspiration, incisional or core biopsy where a major disruption of lymphatic pathways is unlikely to occur. In case of palpable residual disease, we carried out lymphoscintigraphy according to our standard procedure whereas in presence of non-palpable lesion we performed roll associated to a subdermal radiotracer administration [8]. The results obtained in this series of patients demonstrated that lymphoscintigraphy has a high rate of success (98.5%) also w h e n carried out in presence of scar and that subdermal route of injection shows to be superior to the intraparenchymal one, with a SLN visualisation in all patients. As regards the detection rate of the SLN, the results of the present study are not dissimilar from our already published data [24] and confirm that d e r m a l / s u b d e r m a l injection is a more effective route of administration rather than intraparenchymal one. In our opinion this technique may easily overcome the limitations in SLN detection reported by Wong [12] with the peritumoral administration. In relation to the extent of the removed breast tissue neither in patients with excisional biopsy (486 pts) nor in patients with previous quadrantectomy (36 pts) we found a significant difference in the SLN detection related to the elapsed time from breast biopsy, LS and pathological results. We normally avoid to perform a traditional intraoperative examination of the SLNS, whereby only 1 to 3 frozen sections are examined, and the rest of the node is left for the subsequent examination of p e r m a n e n t sections. In this event, a high rate of false-negative intraoperative diagnoses is necessarily expected, with the need for a second operation to complete axillary lymph node dissection in almost 17% of the patients. The above extensive pathological examination of the SLN has been designed to identify in the SLNS even micrometastatic disease (i.e. t u m o u r foci up to 2 m m in size) which can escape detection by less accurate evaluation. A limitation of the present study is that only patients with metastatic SLN received
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Ell]
ACKNOWLEDGEMENTS
[13]
W o r k su] ~ported b y g r a n t s o f t h e Italian A s s o c i a t i o n for C a n c e r R e s e a r c h (AIRC). T h e a u t h o r s t h a n k Dr. D a r i n e G h a n e m for h e r k i n d as,,i!:tance in revising t h e English o f this m a n u script.
[14]
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