Occult breast lesions: A comparison between radioguided occult lesion localisation (ROLL) vs. wire-guided lumpectomy (WGL)

ARTICLE IN PRESS The Breast (2005) 14, 283–289

THE

BREAST www.elsevier.com/locate/breast

ORIGINAL PAPER

Occult breast lesions: A comparison between radioguided occult lesion localisation (ROLL) vs. wire-guided lumpectomy (WGL) R. Nadeema, L.S. Chaglaa, O. Harrisb, S. Desmondb, R. Thindb, C. Titterrellc, R.A. Audisioa,d, a

Department of Surgery, Whiston Hospital, Merseyside, UK Department of Radiology, Whiston Hospital, Merseyside, UK c Cheshire Cancer Network, UK d University of Liverpool, UK b

Received 28 December 2004; received in revised form 19 March 2005; accepted 7 April 2005

KEYWORDS Sub-clinical breast neoplasms; ROLL; Radioguided surgery; Wide local excision; Localisation; Nuclear medicine.

Summary Mammographic screening increases the number of impalpable breast cancers requiring surgical excision. It is important to optimise the localisation technique to remove the smallest amount of tissue, still adequately excising the lesion. The last 65 wire-guided lumpectomies (WGLs) were compared vs. the first 65 radioguided occult lesion localisations (ROLLs) performed for impalpable breast cancers. Data collection included patient’s age, radiological abnormality, preoperative core biopsy, type of primary surgery, length of localisation and excision, hospital stay, cancer size, weight and volume of the excised specimen, clearance margins. All patients were successfully localised with ROLL and WGL. Localisation time was reduced with ROLL (Po0:001). Clear margins were achieved in 83% ROLLs and 57% WGLs (P ¼ 0:001). Pathological cancer size and specimen weight were similar in both groups, although the specimen volume was slightly smaller for ROLL. A total of 74% ROLLs had excellent cosmetic outcomes and 26% good, vs. 55% excellent and 45% good in WGLs. A larger amount of normal breast tissue was excised with WGL, without achieving any better cancer clearance. ROLL provides a feasible alternative to WGL. This quick and simple technique achieves an improved rate of clear margins. & 2005 Elsevier Ltd. All rights reserved.

Corresponding author. Department of General Surgery, Whiston Hospital Prescot, Merseyside, L355DR, UK. Tel.:+44 151 430 1079;

fax: +44 151 430 1891. E-mail address: [email protected] (R.A. Audisio). 0960-9776/$ - see front matter & 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.breast.2005.04.002

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Introduction In 2003, the NHS Breast Screening Programme detected 5.0 invasive cancers per 1000 women, of which 2.7 (54%) were less than 15 mm1; the widespread use of breast imaging has increased the numbers of impalpable breast lesions. More than 13 of the excised breast lesions are clinically occult. Incidence of sub-clinical lesions varies between 17% and 58%2 and has doubled in the last 10 years.3 Precise localisation is an important factor in the surgical management of these small lesions: the small cancer needs to be excised with safe tissue margins, whilst removing the smallest amount of glandular tissue, in order to optimise cosmetic outcomes. Wire-guided localisation and excision is presently the standard technique with some well-known drawbacks, namely, difficult placement of guidewire in a dense breast, wire displacement, inability to reposition, minimal risk of pneumothorax, the procedure is traumatic causing discomfort to the patient, the wire can incidentally be transected, the presence of a foreign body may disturb pathological assessment, injuries associated with the barbs harming the surgical team and pathologist have been reported, and there is an obvious interference with the incision line and surgical approach overall. Alternative techniques have consequently been developed3–7 to assist targetting the sub-clinical lesion and facilitate surgical removal (i.e., intralesional tracer administration, carbon localisation, and intra-operative US). The radioguided occult lesion localisation (ROLL) technique was pioneered in 1996 at the European Institute of Oncology, Milan.8–11 The original technique was significantly modified at our Breast Unit in order to make it simple, affordable, and less cumbersome aiming for a wider uptake by the surgical community11; 99mTc-labelled colloidal human serum albumin is injected directly into the lesion under ultrasound guidance or stereotactic radiographic guidance. The hot area is confirmed and localised allowing a skin incision close to the site of highest radioactivity. The incision is decided on a cosmetic basis, with no need to follow a wire through the breast parenchyma. Following wide excision the cavity is checked for any residual signal. We need not to inject contrast medium to confirm position. Accuracy of the injection is confirmed and documented while the localisation is being performed. We used a much smaller dose of technetium (1 MBq; equals 0.02 mSv which is the same effective dose as for a chest X-ray), and preoperative scintigraphy is omitted. This makes the procedure cheaper and quicker, although a certifi-

R. Nadeem et al. cate of the Administration of Radioactive Substances Advisory Committee (ARSAC) holder is required with details of the procedure, activity per test (in megabecquerels) and effective dose per test. The localisation procedure takes place 1–4 h before surgery; consequently overnight stay can be avoided and costs are constrained. Feasibility and reliability data were previously reported12 for this simplified technique. The ROLL technique has become a standard for several Breast Units world-wide, although there is insufficient data to confirm the superiority of ROLL over wave-guided lumpectomy (WGL); Luini attempted demonstrating this in his early report11 by comparing 30 patients from both groups. Unfortunately, this pioneering report could not specify the advantage of ROLL vs. WGL as the size of the tumour was not stated. Other important issues (i.e., length of localisation, length of surgical excision, costs, cosmetic outcomes) were not reported. The present investigation compares ROLL vs. WGL in relation to the following variables: clearance of excision margins, weight and volume of the excised specimen, duration of procedure, perioperative complication rate, costs and esthetical outcomes.

Patients and methods ROLL was first implemented at our Trust in December 2002. One hundred and thirty consecutive female patients with impalpable breast lesions were treated at our Unit between June 2001 and December 2003: this consecutive series represents an audit between the last 65 patients who had WGL vs. the first 65 patients who had their sub-clinical breast lesion localised with ROLL. As it is our practice to aim for breast conservation whenever possible, the present series also includes eight patients (five ROLLs and three WGLs) who had their tumour localised after neo-adjuvant chemotherapy. In keeping with our standards, these patients had a metal coil (MReye, Cook Inc.s) inserted into the core of the tumour before they were started on neo-adjuvant chemotherapy in case of complete remission and tumour disappearance. Tumour localisation was conducted by three dedicated breast radiologists and surgical procedures were performed by four breast surgeons. Both localisation and surgical excision were

ARTICLE IN PRESS Occult breast lesions Table 1

Definitions.

Vt V is

Volume of the tumour Volume of an ideal specimen’’ with 1 cm safe margins Volume of the excised specimen V exc =V is V exc =V t

V exc R R

’’

purpose of providing an estimate of the tumour volume. The volume of the excised specimen ðV exc Þ was calculated as the product of the 3 dimensions recorded by the pathologists. It is our policy to aim for gross margins of 1 cm around the tumour during surgical excision; accordingly and in order to express the concentricity of the tumour within the specimen, we computed the ideal volume’’ required to excise the tumour within a 1 cm safety margins all around ðV is Þ by means of the same formula, in keeping with previous reports13 (Table 1). Furthermore, the ratio between the volume of the excised specimen and the ideal volume was computed with the formula R ¼ V exc =V is ; similarly the ratio between the volume of the excised specimen and the tumour volume was computed as R ¼ V exc =V t . Costs were computed in British Sterling (£) and cosmetic results were assessed in clinic during follow–up visits by means of a four-point scoring system of breast cosmesis14 with the results being appraised before adjuvant radiotherapy was started. Microsoft Access, Microsoft Excel and SPSS were used to store and analyse the data. T-tests, Chisquared and Mann–Whitney tests were used where appropriate to test the significance between the two groups. ’’

performed by a randomly assigned specialist with no resultant selection bias. We have considered both therapeutic excisions (115 patients; 88%) and diagnostic ones (15 patients; 12%) as it is our policy to consider small but suspicious lesions as malignant ones, in order to avoid a second operation when the specimen can be safely removed in the first instance. 99mTc-labelled colloidal human serum albumin was injected directly into the breast lesion with an 18–21 gauge needle under US or stereotactic guidance before the patients were sent to theatre (1–4 h). The site of isotope injection was confirmed by direct visualisation under US, or by the presence of the tip of the needle within the target area under stereotactic control. Subsequently, the hot area at the site of injection was identified in the induction room by means of a g-probe minutes before the patient was anaesthetised. The hot spot corresponds to the area of maximum radioactivity; the g-probe measures the radioactivity in counts per second and provides audible as well as visual signals which are digital and graphical. The skin incision was placed at the most convenient site for the surgical excision, which could take place a few centimetres away from the lesion for cosmetic purposes (i.e., sub-mammary/ axillary fold). The targeted wide excision was performed and the complete removal of radioactivity confirmed with the g-probe, as was the presence of the hot spot within the excised specimen; then the specimen is sent for X-ray to confirm the presence of the lesion. Clearance margin Z1 mm and Z5 mm were accepted for invasive cancer and DCIS, respectively. Clinical data was collected in relation to age, radiological abnormality, pre-operative core biopsy, type of primary procedure, length of localisation and excisional procedure, hospital stay, cancer size, weight and volume of the excised specimen, clearance margins and final pathological diagnosis including type and grade of tumour, lymph node status, peri-operative complications, type of secondary procedure if required, use of neo-adjuvant chemotherapy. For the purpose of defining the volume of the tumour ðV t Þ, the excised specimen ðV exc Þ, as well as the ideal specimen’’ ðV is Þ, we utilised the following formulae: the theoretical volume of tumour ðV t Þ was computed as V t ¼ ðp=6Þd 3 where d is the maximum diameter of the tumour as measured by the pathologist on final histology (Table 1). We have assumed the tumour to be spherical in keeping with previous reports13 as the slight difference in the cancer’s shape does not alter the volume, for the

285

Results The two study groups were comparable for age, radiological findings, pre-operative pathological diagnosis (B1-5) and type of surgical procedure (Table 2). Forty-nine ROLL patients were localised with US, and 16 by stereotactic technique; this compares to 38 and 27, respectively, in the WGL group (P ¼ ns). The localisation time, either under US or stereotactic guidance, was significantly reduced with ROLL: it lasted a median of 6 min (range: 5–7 min) and 12 min (range:10–15 min), respectively, in the

’’

ARTICLE IN PRESS 286 Table 2

R. Nadeem et al. Clinical features of patients localised by ROLL and WGL.

Variables

ROLL median (range)

WGL median (range)

Overall no. patients Age (yr) Radiological abnormality Micro-calcifications Micro-calcification and stromal deformity Stromal deformity Asymmetrical density Mass Pre-operative core biopsy B1 B3 B4 B5 Localisation time (min) US Stereotactic Localisation technique US Stereotactic Type of primary procedure Lumpectomy Lumpectomy + axillary dissection Time of procedure (min) Post-operative hospital stay (days) Pathological size of tumour (cm) Weight of specimen (g) Final pathological diagnosis Invasive ductal Invasive with associated DCIS Invasive tubular Invasive lobular Invasive lobular + LCIS DCIS LCIS Margins Clear Involved Minimal clearance (mm) Cosmetic outcomes Excellent Good

65 56 (36–77)

65 58 (37–85)

14 2 2 1 46

22 1 5 1 36

— — 6 59

1 1 7 56

6(5–7) 12 (10–15)

15 (15–17) 20 (20–25)

49 16

38 27

13 52 30 (20–45) 2 (1–3) 15 (4–50) 38 (6–128)

28 37 30 (25–60) 2 (1–4) 14 (3–50) 50 (7–167)

29 26 – – 1 9 –

27 18 2 1 2 14 1

54 11 4 (1–12)

37 28 3 (1–10)

48 17

36 29

P ¼ 0:066

Po0:001 Po0:001 P ¼ 0:040

P ¼ 0:013

Po0:616 P ¼ 0:567 P ¼ 0:182 P ¼ 0:299

P ¼ 0:001

was larger than that in WGL (696 mm3) (P ¼ 0:008). Similarly, the ideal volume’’ to be excised for the ROLL patients was slightly larger (P ¼ 0:01). This did not require a significantly larger specimen to be excised for the ROLL group; the median specimen weight was not different for the two groups (ROLLs: median 38 g; range 6–128 g; WGL: median 50 g; range 7–167 g). Also, the median volume of the excised specimen was smaller in the ROLL group than for WGL (82 500 mm3 vs. 109 688 mm3) (P ¼ ns) (Table 3). ’’

ROLL group, as compared to 15 min (15–17) and 20 min (20–25) for WGL (Po0:001). Conversely, the length of the surgical procedure was not reduced with ROLL. No difference was noticed in post-op hospital stay or complication rate between the two groups (P ¼ 0:567 and 0.514, respectively). Small differences were noticed when comparing the cancers’ size and weight: median pathological size of the tumour was larger in the ROLL group (15 mm) than WGL (14 mm), hence the median tumour volume in the ROLL group (1766 mm3)

P ¼ 0:870 P ¼ 0:064

ARTICLE IN PRESS Occult breast lesions Table 3

287

Volume analysis of patients localised by ROLL and WGL.

Variables

ROLL median (range)

WGL median (range)

Patients with clear margins V t ðmm3 Þ V is ðmm3 Þ V exc ðmm3 Þ R R Patients with involved margins V t ðmm3 Þ V is ðmm3 Þ V exc ðmm3 Þ R R

54 1766 (34–33 523) 21 490 (7230–113 141) 82 500 (6300–300 000) 3.73 (0.28–18.28) 72.31 (1.19–1487) 11 3054 (34–65 475) 28 742 (1768–179 663) 54 999 (15 400–178 500) 0.90 (0.24–84) 9.32 (0.92–2275)

37 696 (33–8172) 14 143 (5569–47 658) 109 688 (5381–507 000) 7.18 (0.24–39.75) 111.94 (3.05–3304) 28 1765 (14.12–82 480) 22 423 (8172–212 256) 73 125 (15 200–325 000) 3.26 (0.61–11.42) 34.42 (1.58–2833)

P P P P P

¼ 0:008 ¼ 0:010 ¼ 0:173 ¼ 0:008 ¼ 0:068

P P P P P

¼ 0:290 ¼ 0:245 ¼ 0:090 ¼ 0:016 ¼ 0:041

’’

V t —Volume of the tumour. V is —Volume of an ideal specimen’’ with 1 cm safe margins. V exc —Volume of the excised specimen. R —V exc =V is . R —V exc =V t .

Furthermore, a significantly larger number of ROLL patients 54/65 (83%) had clear margins as compared to 37 56 (57%) WGL patients (P ¼ 0:001). Amongst patients with clear margins, R* and R** were 3.73 and 72.31, respectively, in ROLL group, and 7.18 and 111.94 in WGL group. An obvious difference is noticed here (P ¼ 0:008). Further more, when only patients with involved margins are considered, R* and R** were 0.90 and 9.32 in ROLL group, and 3.26 and 34.42, respectively, in WGL group. This implies that, although the WGL group had a larger excision with a much wider amount of healthy glandular tissue removed, this did not help to improve the oncological adequacy of the cancer removal. Both differences are statistically significant (P ¼ 0:016 and 0.041). Six of the eleven patients with involved margins in the ROLL group had to be offered a mastectomy because of the extensive nature of DCIS, and five patients underwent a re-excision of the involved margins. In the WGL group, 13 patients underwent mastectomy while 15 had a re-excision of the involved margins. One patient developed a post-operative wound infection in each group. The radiation exposure with ROLL was carefully monitored with dose measurements to the surgeon’s hands during the procedure and radiographer’s hands during X-raying of the specimen, showing no traceable activity (data not reported). When cosmetic results are taken into account, 74% ROLL patients had excellent and 26% good outcomes, compared to 55% excellent and 45% good for the WGL group; this does suggest a trend toward a cosmetic advantage for the ROLL technique

(P ¼ 0:064) but a larger series would be required to statistically confirm this.

Discussion Precise localisation is the most important factor in the accurate surgical removal of clinically occult breast lesions, as the amount of tissue excised is inversely proportional to the cosmesis.12 Accurate targeting is important in achieving better concentricity of the impalpable lump, minimising the amount of healthy breast tissue un-necessarily excised, whilst preserving safe tissue margins, and optimising cosmetic results. Of the various localisation methods, WGL is the standard in the UK. Several problems with WGL have been reported, such as difficult wire placement in dense breasts, difficulties re-positioning, dislodgement, transection and wire loss during surgery, interference with the surgical approach and incision, rare risk of a pneumothorax, patient discomfort, and presence of a foreign body interfering with pathological dissection. Other techniques have consequently been developed such as intralesional tracer administration,7 skin marking with ultrasound, intra-operative US,3,4 and carbon localization.5,6 ROLL was first developed in 1996 at the EIO, Milan, to overcome some of the disadvantages of WGL. Reported advantages are10,11,15: precise localisation and accurate surgical removal, reduction in the tissue damage within the final pathological specimen, accurate frozen section (in the case

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R. Nadeem et al.

a differential diagnosis is required between DCIS and invasive cancer), improved rate of clear margins avoiding the emotional trauma of another operation, reduced size of the excised specimen, better concentricity of the lesion, increased patient comfort, decreased operative time, and reduced rate in re-do surgery reducing costs.10,11,16 Our experience with the implementation of ROLL at our District General Hospital has been previously reported.12 A prospective audit was set up, enrolling the last 65 WGLs and comparing these findings with the first 65 ROLLs. Although we accept the two groups are not evenly balanced, as we were still in a learning phase for the new technique, we can now provide evidence of some advantages of the ROLL technique. Whether US or stereotactic method was used, the localisation time was halved with ROLL; no control mammogram is needed after localisation, allowing reduction in both costs and radiation dose. It might be worth mentioning that the effective glandular dose for a mammogram is 1–2 mSv, while the effective dose for a ROLL localisation is 9.25 mSv. The two comparative groups had similar median pathological cancer maximum diameters (ROLL 15 mm, range 4–50 mm; WGL 14 mm, range 3–54 mm), and specimen weight. This is reflected in a non-significant difference in cancer volume between the ROLL group (median volume 1768 mm3) and WGL group (median volume 696 mm3). Finally, the median volume of the excised specimen was similar in both groups. A larger number of inadequate excisions was recorded with WGL, as 43% WGL patients had o1 mm safety margins vs. 17% in the ROLL group (P ¼ 0:001). A median ratio (R*) of 3.73 for ROLL patients with clear margins was computed, as opposed to 7.18 in the WGL group; R** was 72.31 and 111.94 in the two groups, respectively, a larger volume of normal breast tissue was being excised in WGL group compared to ROLL without achieving any better clearance. R* is 0.90 in patients with involved margins in ROLL group and 3.26 in WGL group. This implies that the excised specimen was smaller than the ideal volume’’ to be removed in ROLL group, thus leading to involved margins. Conversely, in the WGL group, in spite of removing almost three times the ideal volume’’, margins were still involved (P ¼ 0:016). R** is 9.32 in ROLL group compared to 34.42 in the WGL group indicating a reduction in the excised volume of 8 times in ROLL group and only 3.25 times in WGL: in addition to the volume of the excised specimen some other factor also plays a

vital role in improving the rate of clearance margins, such as the concentricity of the tumour within the excised specimen. This is in keeping with Luini’s findings proving that ROLL is associated with better concentricity as compared to WGL.11 Excision of impalpable breast lumps should be considered a three-dimensional technique with the ROLL technique simplifying the three-dimensional dissection. Cosmetic outcomes, appear to favour ROLL, as measured by means of a popular scoring system. This experience confirms previous reports and adds further evidence in favour of this technique. ROLL can easily be implemented and we would be pleased to make ourselves available for any training or practical suggestions.

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