Introduction There is an increasing use of advanced radiologic imaging for staging and surveillance of solid malignancies resulting in the identification of subclinical non-palpable metastases. Radioactive seed localization (RSL) is a safe and accurate method of localization of non-palpable breast cancers. The aim of this study was to evaluate the expansion of RSL to non-breast lesions.
Methods We conducted a retrospective review of a prospective database of all RSL procedures performed at our institution from January 2007 to April 2010.  All RSL performed for breast lesions were excluded.
Results Eight patients underwent radiologic placement of a ¹²⁵I seed using ultrasound or CT guidance. Sites included the upper leg and shoulder, as well as, the internal mammary, infraclavicular and axillary lymph nodes. The mean size of the resected specimen was 2.74 cm in greatest dimension (range 0.6-7.1 cm). The surgeon used a handheld gamma probe for guidance to excise the seed and lesion with negative margins and minimal morbidity.
Conclusions RSL is a safe, accurate, and effective technique for the localization and excision of non-palpable non-breast lesions. RSL has the potential to be adapted to many lesions amenable to a percutaneous approach as it permits convenient and accessible localization of the lesion via gamma probe, avoids the issues of wire management with wire localization, and maintains radiation safety through low radioactive seed doses.

The Use of Radioactive Seed Localization for Non-Palpable Non-Breast Lesions

Travis E. Grotz, MD,¹ Cindy L. Tortorelli, MD,² Amy C. Degnim, MD,¹ Judy C. Boughey, MD,¹ Dana H. Whaley, MD,^2‚ and James W. Jakub, MD¹

1. Department of Surgery, Mayo Clinic, Rochester, Minnesota.
2. Department of Radiology, Mayo Clinic, Rochester, Minnesota.

Contact: James W. Jakub, MD E-mail This e-mail address is being protected from spambots. You need JavaScript enabled to view it .

Citation: Grotz TE, Tortorelli CL, Degnim AC, Boughey JC, Whaley DH, and Jakub JW. The use of radioactive seed localization for non-palpable non-breast lesions. J Surg Radiol. 2010 Oct 1;1(2). Download PDF The Use of Radioactive Seed Localization for Non-Palpable Non-Breast Lesions 1730 Kb Received June 19, 2010. Accepted July 21, 2010. Epub July 31, 2010. Copyright: © 2010 Surgisphere Corporation. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Contents - Introduction - Materials and Methods - Results - Discussion - Disclosures - References

---

Introduction

The role of routine surveillance to detect metastatic foci of cancer before they are clinically appreciated is controversial. A consistent argument against this approach contends that finding stage IV disease before clinical detection does not improve survival. In fact, it may serve only to inform patients they have incurable disease while they are asymptomatic, as opposed to symptomatic disease presenting just a few months later, had routine imaging not been performed. Others argue that, in some patients, routine surveillance can identify clinically occult locoregional or even oligometastatic stage IV disease that may result in improved survival if completely resected. Though this debate for individual solid tumor sites has not been resolved by evidence based approaches, the fact remains that advanced radiologic imaging for patients with high risk lesions is being performed as part of follow-up on a regular basis. The result is an increase in the identification of clinically occult single sites of metastasis in some patients.¹

These sites of clinically occult metastasis may be diagnosed with [¹⁸F] fluorodeoxyglucose (FDG) positron emission tomography (PET), computed tomography (CT), ultrasound (US), or magnetic resonance imaging (MRI). This early detection challenges the radiologist to localize the lesion and direct the surgeon to allow intraoperative identification of the site for resection. Localization modalities include wire localization, intralesional injections of dye, intraoperative ultrasound guidance, and marking the overlying skin with indelible ink.^2-5 Radioactive seed localization (RSL) is a novel alternative to the above modalities for the localization of non-palpable lesions. Several studies have demonstrated the safety of the use of a ¹²⁵I titanium seed for localization of non-palpable breast lesions not only for the patient, but also the surgeon, surgical team, radiologist, and pathologist.^6-9 RSL utilizes technology currently available in most operating rooms, specifically, a handheld gamma probe. These probes are commonly employed for sentinel lymph node (SLN) biopsy. They offer the advantage of providing constant real-time feedback to the surgeon allowing continuous reorientation to the non-palpable area of concern. When used for breast cancer, the RSL technique has resulted in retrieval of the targeted lesion and seed 100% of the time.^7-9

Given the success of RSL in non-palpable lesions of the breast, it seems only natural to expand this to other non-palpable lesions throughout the body. However, only one previous case report describes the use of RSL to localize in-transit metastasis deep within the subcutaneous tissue of the lower extremity.¹⁰ The aim of this study is to further describe the role of RSL to provide intraoperative localization for a variety of non-palpable lesions.

Materials and Methods

This retrospective study was approved by the institutional review board and all patients consented to the use of their medical records for research. Three hundred and twenty patients were identified from a prospective database of patients who underwent RSL at the Mayo Clinic, Rochester between January 2007 and April 2010. Over these 40 months the overwhelming majority of RSL procedures were utilized for the care of primary lesions in the breast (312 patients). In eight (2.5%) patients the indication for RSL was the localization of a non-palpable lesion outside of the breast. We retrospectively reviewed the medical records, radiological studies, operative reports, and pathological specimens of these eight patients. Given the small sample size only descriptive statistics were used.

Results

Radioactive Seed Localization

¹²⁵I labeled titanium seeds are FDA-approved for the interstitial treatment of prostate cancer. The use of the ¹²⁵I seeds for localization is an off-label use. RSL was performed as previously described¹¹ with 0.158 to 0.277 mCi of ¹²⁵I encased in a small (4.5 x 0.8 mm) titanium seed; this isotope has a half life of 60 days. The radioactive seed is loaded into an 18-gauge needle by the radiologist after occluding the tip with sterile bone wax. The needle is then introduced into the target lesion using radiologic imaging (ultrasound, CT, or mammography) guidance. The seed is deployed by advancing the stylet. The needle is withdrawn and accurate placement of the seed is confirmed upon repeat imaging. The patient is then discharged and reports for surgery on the prescribed day (0-3 days later) with no restrictions.

Standard intraoperative handheld gamma probes were used by the surgeon to identify the seed within the target tissue. Most gamma probe systems allow the specific detection of numerous isotopes. By choosing the ¹²⁵I setting on the gamma probe, the surgeon can selectively identify and isolate the 27 keV source, thus allowing simultaneous lymphatic mapping with ⁹⁹Tc without interference between the two isotopes. The gamma probe and seed provide constant audible feedback during the procedure allowing continuous reorientation of the specimen. After removal, the gamma probe is used to confirm the removal of the seed and absence of residual radioactive activity in the surgical field. No signage or monitoring badges are required in the operating room. A specimen radiograph may be obtained to document removal of the seed and position within the specimen. The specimen is then transported to the pathology department where the pathologist dissects the seed from the specimen and places it in a lead container. Standard intraoperative pathologic processing is performed, including frozen section analysis at our institution. A member of the nuclear medicine staff retrieves the seed for long term storage and decay. No room signage or monitoring badges are necessary in the pathology suite.

Cases

Eight patients underwent RSL for non-palpable, non-breast lesions during the study period. The mean age of the patients was 47 years of age (range 25-75 years old) at the time of the procedure, and the median follow up was 9.4 months (range 2-17.5 months). Five patients were female and three were male. Three patients had a primary diagnosis of melanoma, four patients had breast cancer, and one patient had an adnexal apocrine adenocarcinoma (Table 1). All of the radioactive seeds were placed under ultrasound guidance except one. CT was utilized secondary to inability to definitively identify the lesion on ultrasound.

 

---

 

Table 1. Clinical characteristics of 8 patients who underwent RSL of non-palpable lesions outside of the breast.

The time between placement of the seed and surgical resection was a mean of 15 hours with a range of 2-66 hours. The amount of ¹²⁵I in each seed ranged from 0.158 mCi to 0.277 mCi, with a mean of 0.21 mCi, and all seeds were successfully recovered. The mean size of the resected specimen in greatest diameter was 2.74 cm (0.6 cm to 7.1 cm). Frozen section intraoperative pathologic analysis was performed, and the final margins were negative in all cases with no patients requiring a second operative intervention. However, two re-excisions were necessary under the same anesthetic secondary to a close margin (1 mm) identified intraoperatively. One patient who underwent simultaneous RSL of an intransit metastasis of the adductor magnus and inguinal lymphadenctomy developed a postoperative wound infection of the inguinal incision that was managed with oral antibiotics as an outpatient. Four patients did not undergo combined procedures and were discharged the day of surgery; the other four patients underwent simultaneous procedures requiring 1- to 2-day hospitalizations (mean LOS – 1.25 days). There were no mortalities and only one superficial wound infection as described above associated with this procedure.

In this series, two intransit melanoma metastases, one internal mammary lymph node, two infraclavicular lymph nodes, and three axillary lymph nodes were localized using the radioactive ¹²⁵I seeds. Both intransit metastases were located within the deep tissue of the upper thigh; one in the subcutaneous tissue and the other was intramuscular in the adductor magnus. The majority (75% n=6) of the resected lesions were for metachronous locoregional metastases diagnosed on surveillance PET (n=5) or MRI (n=1) imaging a mean of 48.6 months (range 1.4 - 126.4 months) after diagnosis. The two synchronous lesions were also identified on preoperative staging PET scan. The primary malignancy was histologically confirmed in all cases, however, none of the target lesions localized by RSL were biopsied preoperatively. In all cases there was no evidence of distant metastases. The final pathology confirmed oligometastatic disease in all cases except two. Both of these were reactive axillary lymph nodes with suspicious surveillance imaging (PET, MRI, and US) in patients who had previously undergone axillary lymphadenectomy without adjuvant radiation.

Figure 1. F-18 FDG PET/CT scan with CT fusion imaging demonstrating a new soft tissue nodule in the medial aspect of the distal right thigh with avid FDG uptake measuring 2.3 cm transverse x 1.7 cm AP. Suspicious for in-transit metastatic melanoma.

Figure 2. A. Ultrasound guided ¹²⁵I seed placement into an infraclavicular lymph node (top). B. The seed appears as a linear echogenic focus with the node (bottom).

 

Figure 3. A. CT guided ¹²⁵I seed into suspicious internal mammary lymph node (top). B. Seed identified just anterior to suspicious the internal mammary lymph node on post localization CT (bottom).

 

---

 

Discussion

The advantages of RSL of non-palpable breast cancers have been well described.¹¹ However, this is only the second report and first case series of the use of RSL for non-palpable lesions outside of the breast. We have demonstrated the safety and accuracy of RSL in this small series as we were able to accurately identify the target lesion and obtain negative margins in all cases using RSL with minimal morbidity. RSL provides a very focal point source for localization that allows the intraoperative identification of lesions as small as 6 x 4 x 3 mm in our study and 2 x 5 mm in a previous case report.¹⁰ Radioactive seed placement was performed the morning of surgery in some cases and up to three days prior to the operation in others, providing improved patient convenience. Uncoupling the operative and radiologic scheduling eliminates many conflicts, avoids the need for same day surgery, and allows a first case start time. The seeds were easily placed within the lesion in all instances using either ultrasound or CT guidance with no lost or displaced seeds. The technique of RSL uses a skill set familiar to both radiologists and surgeons. Needle localization with the radioactive seed employs standard image-guided percutaneous approach. Correspondingly, for the operative approach, the guidance is similar to SLN biopsy with which most surgeons are comfortable. Therefore, RSL was easily incorporated into a busy academic surgical practice.

Intraoperative ultrasound for guidance is an option for some of these lesions but is limited in cases that cannot be visualized by this technology. Also, many surgeons are not adequately trained or comfortable identifying these lesions intraoperatively without reliance on a localization device. As a result, many of these lesions may require the presence of a radiologist in the operating suite if the surgeon is not specifically trained in ultrasonic evaluation, especially in small, difficult to visualize lesions. Wire localization (WL), another localization technique, has many disadvantages including wire misplacement, dislodgment and migration during post-localization imaging and patient transportation, as well as, wire transaction intraoperatively.^5,12-14 In the case of wire transection, not only does the surgeon lose all localization, but there is a potential for a retained foreign body within the patient. The distinct disadvantage to WL is that the ideal trajectory of skin entry to the target for the radiologist to place the wire may be less then optimal for surgical incision planning. In addition, the tip of the wire in the soft tissue is not palpable eliminating any feedback to assure the surgeon is beyond the tip before coming across the specimen. The accuracy of marking the skin overlying the lesion with indelible ink may be ideal in certain locations such as the internal mammary nodes but is fraught with potential operative mishaps in many anatomic sites due to changes in patient position and inability to appreciate the exact depth from a cutaneous marking. Injection of dye into the soft tissue for localization of non-palpable lesions is limited by its diffusion into the surrounding tissue.

RSL has been demonstrated to be such an accurate method for localization of non-palpable breast cancers, as Gray et al. demonstrated in a randomized trial, that fewer additional margin resections were needed compared to WL (26% vs. 57%).⁷ A retrospective study demonstrated a 35% (p = 0.01) relative improvement in the rate of negative margins in the first specimen and a 62% (p = 0.01) reduction in the rate of reoperation for positive margins.8 A subsequent prospective multi-institutional trial confirmed a lower positive margin rate with RSL compared to WL.⁹ In addition, RSL is efficient as it does not increase the operative time or the localization time.⁷ RSL is convenient as it can be scheduled days in advance (up to 5 days preoperatively at our institution) and therefore, convenient for the patient, surgeon, and radiologist. RSL also allows the radiologist the ability to approach the lesion from the easiest and safest angle without regard for the need of the surgeon to incorporate the wire trajectory (if using WL) in their incision. These factors resulted in RSL receiving higher convenience scores by the patient than WL (8.5 vs 7.4 p = 0.02).⁹ Handheld guidance by the gamma probe to identify the ¹²⁵I seed is intuitive and provides constant feedback allowing the surgeon to determine the appropriate depth of the lesion ensuring when it is safe to transect the specimen under the deep margin of excision. No other current localization approach for non-palpable lesions provides this advantage.

RSL has been demonstrated to be a safe method of localization. With this modality the radioactive seed is being utilized for localization and not as a therapeutic intervention for cancer. In brachytherapy for prostate cancer multiple (50-110) ¹²⁵I seeds are utilized with higher radioactive activity (12.6-16.7 MBq) for a therapeutic radiation dose of 145 Gy.¹⁵ In contrast RLS utilizes one seed with less than 3.7 MBq for a short duration. The peak dose to residual tissue given by a 3.7 MBq seed excised 24 hours after implantation within an approximately 2 cm specimen results in as little as 2.8 cGy to the residual tissue.⁶ The radioactive dose to the residual tissue decreases substantially as the specimen size increases secondary to tissue absorption and the inverse square law. Regarding radiation exposure to the surgeon, surgical team, pathologist, and radiologist, given the seed’s low strength, the actual exposure at the skin surface is 0.2 mGy and, therefore, no special radiation safety precautions are routinely needed.⁶

The numerous advantages of RSL over conventional localization techniques in non-palpable breast cancers warrant further investigation of this novel technique for non-palpable lesions outside of the breast. This case series builds upon a previous case report to establish RSL as a viable option for localization of non-palpable oligometastatic disease in various regions of the body.¹⁰ As complete surgical resection becomes increasingly incorporated into the multidisciplinary management of patients with stage IV cancers, such as breast and melanoma, the need for an efficient and simple localization technique becomes more important. The results of this case series support the conclusion that RSL has the potential to be adapted to most lesions amenable to a percutaneous approach. However, these results are limited as this is a retrospective single institutional study and is, therefore, subject to selection bias. The small sample size also limits the confidence to make conclusions. Nevertheless, it should serve as an impetus for prospective studies with larger sample sizes to further investigate and validate the potential diverse applications of RSL. In conclusion, we have found RSL to be a promising technique that allows for the localization and excision of radiographically-identified but clinically occult lesions.

Disclosures

The authors have no disclosures or conflicts of interest related to this manuscript.

References

1. Bastiaannet, E., et al., Prospective comparison of [18F]fluorodeoxyglucose positron emission tomography and computed tomography in patients with melanoma with palpable lymph node metastases: diagnostic accuracy and impact on treatment. J Clin Oncol, 2009. 27(28): p. 4774-80. CrossRef PubMed
2. Ueno, E., et al., Ultrasonically guided biopsy of nonpalpable lesions of the breast by the spot method. Surg Gynecol Obstet, 1990. 170(2): p. 153-5. PubMed
3. Hall, F.M. and H.A. Frank, Preoperative localization of nonpalpable breast lesions. AJR Am J Roentgenol, 1979. 132(1): p. 101-5. PubMed
4. Makuuchi, M., H. Hasegawa, and S. Yamazaki, Intraoperative ultrasonic examination for hepatectomy. Ultrasound Med Biol, 1983. Suppl 2: p. 493-7. PubMed
5. Homer, M.J. and E.R. Pile-Spellman, Needle localization of occult breast lesions with a curved-end retractable wire: technique and pitfalls. Radiology, 1986. 161(2): p. 547-8. PubMed
6. Pavlicek, W., et al., Radiation safety with use of I-125 seeds for localization of nonpalpable breast lesions. Acad Radiol, 2006. 13(7): p. 909-15. CrossRef PubMed
7. Gray, R.J., et al., Randomized prospective evaluation of a novel technique for biopsy or lumpectomy of nonpalpable breast lesions: radioactive seed versus wire localization. Ann Surg Oncol, 2001. 8(9): p. 711-5. CrossRef PubMed
8. Gray, R.J., et al., Radioactive seed localization of nonpalpable breast lesions is better than wire localization. Am J Surg, 2004. 188(4): p. 377-80. CrossRef PubMed
9. Hughes, J.H., et al., A multi-site validation trial of radioactive seed localization as an alternative to wire localization. Breast J, 2008. 14(2): p. 153-7. CrossRef PubMed
10. Fleming MD, P.B., Hansen AJ, Gray RJ, Patel MD., Radioactive seed localization for excision of melanoma. Radiology Case Reports, 2006. 1(8): p. 54-57. CrossRef
    
11. Jakub, J.W., et al., Current status of radioactive seed for localization of non palpable breast lesions. Am J Surg. 199(4): p. 522-8. CrossRef PubMed
12. Bronstein, A.D., R.F. Kilcoyne, and R.E. Moe, Complications of needle localization of foreign bodies and nonpalpable breast lesions. Arch Surg, 1988. 123(6): p. 775-9. PubMed
13. Homer, M.J., Transection of the localization hooked wire during breast biopsy. AJR Am J Roentgenol, 1983. 141(5): p. 929-30. PubMed
14. Davis, P.S., et al., Migration of breast biopsy localization wire. AJR Am J Roentgenol, 1988. 150(4): p. 787-8. PubMed
15. Moule, R.N. and P.J. Hoskin, Non-surgical treatment of localised prostate cancer. Surg Oncol, 2009. 18(3): p. 255-67. CrossRef PubMed

< Prev		Next >