The non-palpable breast lesion is usually detected through screening mammography or other imaging techniques, and accurate localization and excision during surgery is challenging without guidance [1, 2]. Radioactive Seed Localization (RSL) has emerged as a significant advancement in breast surgery for the precise removal of non-palpable breast lesions [3]. By utilizing a small, biocompatible radioactive iodine seed, surgeons can accurately pinpoint the lesion's location in real-time, improving other localization techniques such as wire localization, radar reflectors, magnetic seeds and Radio-frequency identification tags [4–7]. The seed emits low radiation levels and is placed within or adjacent to the non-palpable breast lesion under imaging guidance before surgery. During the operation, a gamma probe detects the radiation from the seed, leading the surgeon directly to the target tissue [8].

Approximately 60% of breast cancers are non-palpable lesions, and due to the large number of breast surgeries requiring localization, the use of RSL has increased over the past decade [9, 10]. RSL yields comparable outcomes compared to wire-guided localization [11] but provides the flexibility of placement prior to the day of the procedure, enhancing the efficiency of scheduling for both radiology and the operating room and also improving patient satisfaction [4, 12–14]

The intended audience for this paper includes medical institutions with existing or planned RSL programs, as well as regulatory agencies seeking to update RSL-related guidance [15]. This paper provides a retrospective review of an established RSL program encompassing over a decade's worth of experience with a focus on process improvements learned from over 25 000 cases. In this review, we discuss both best practices related to the initial activity of the seeds upon ordering and the frequency of orders to minimize the dose to the patient's breast while maintaining viable RSL seed activity. Furthermore, updated models are presented to assess radiation dose to the breast of patients implanted with RSL seeds based on the durations of seed implant, implant depth and implant activity. Lastly, program evolution over time through changes in RSL indication and localization methodologies over the past decade are discussed.

2.1. Institutional review board approval and study period

Before conducting this study, compliance with the Health Insurance Portability and Accountability Act (HIPAA) was established. The Institutional Review Board granted a waiver for this HIPAA compliant study. A retrospective review of all mammographic and ultrasound-guided I-125 RSL procedures performed between 1st January 2011 and 31st December 2021 was conducted. During this timeframe, 25 722 seeds were implanted in 18 916 patients before lumpectomy or excisional biopsy. All relevant clinical and pathologic data reviewed in this paper were recorded and analyzed from the electronic medical record.

2.2. Description of RSL seeds

In recent years, RSL has proven to be a viable and effective method for preoperative localization due to the physical properties of I-125, which was chosen for its advantageous characteristics. Firstly, RSL can provide accurate and precise localization of target lesions. Secondly, it is associated with minimal radiation exposure to patients and medical staff while maintaining high detectability [4, 16, 17]–an essential trait for maintaining safety during the procedure and minimizing long-term risks associated with radiation. Thirdly, the radioisotope has an appropriate half-life of 59.4 d [18], allowing for adequate lesion localization while not requiring immediate removal. By contrast, Tc-99 m has a much shorter half-life (approximately 6 h) [19], which may necessitate same-day or next-day surgery and limit scheduling flexibility. This extended half-life provides a suitable time window for the surgical team to schedule the excision and ensures a stable signal throughout the localization process.

High detectability of I-125 seeds is achieved using gamma probes during surgery (figures 1(C) and (D)). These sensitive, handheld probes can precisely localize the low levels of radioactivity emitted by I-125 seeds during surgery, which aids in incision placement and the identification and subsequent excision of the lesion [20]. Furthermore, I-125 seeds are also easily distinguishable from other medical radionuclides due to their specific energy spectrum (35.5 keV) produced by nuclear decay to Te-125. This ability to differentiate between radionuclides is essential when a patient undergoes additional nuclear medicine procedures, such as sentinel lymph node mapping with Tc-99 m. Furthermore, a lead collimated cap is placed on the tip of the probe into give the surgeon better precision in locating the seed. The interaction of radiation within the probe's sensitive volume is proportional to the energy of the incident photon. Photons with higher energies create more radiation interactions within the probe. The probe's electronic system can be configured to count photons with energies inside a specific energy window, effectively filtering out photons with energies outside this range. Consequently, the probe may differentiate between radionuclides only if they emit photons different energies. The ability to differentiate between radiation decay signals helps to accurately locate of the target lesion despite extraneous radiation sources.

Figure 1. The RSL needle assembly and radiation detection apparatus. (A) An 18-gauge, 7 cm needle containing a radioactive I-125 seed for breast localization and its stainless-steel shielding. Because depth is such an important consideration in RSL procedures, the needle markings denote depths ranging from 1 to 6 cm. (B) A magnified view of the radioactive seed encased in bone wax, a transparent plastic spacer, and the RSL needle. The hash markings in the needle are 1 cm apart, which aids in placing seeds at the correct depth. (C) The RSL wireless probe with a collimated radiation detector. (D) A hospital pathologist uses an RSL monitor to show 23 547 counts per second from a probe held near a tissue specimen containing a radioactive I-125 seed. The 200 counts per second on the display denotes the background subtraction level (Photo credit: M. Bellamy).

Download figure:

Standard image High-resolution image

The I-125 seed, bone wax and a plastic spacer are typically encased within a titanium shell, allowing for easy placement and non-migratory stability within the tissue, as shown in figures 1(A) and (B). The seed is then inserted percutaneously into the lesion using ultrasound or mammography modalities for pre-implant imaging and post-implant confirmatory imaging. In terms of magnetic resonance imaging safety, the tungsten core is MR conditional while the titanium shell is MR safe. Performing magnetic resonance imaging (MRI) guided RSL localization in the breast is possible with some preparation [21–23].

Overall, the utilization of I-125 in RSL has proven to be a valuable addition to the oncology field, enhancing the accuracy and efficiency of tumor localization while minimizing radiation exposure [4, 17, 24].

2.3. Quantity of radioactive material (RAM) ordered for RSL seeds

The primary responsibility of medical health physics departments is to ensure the safety of medical personnel and patients by minimizing exposure to unnecessary radiation through fundamental radiation protection principles [25, 26]. Planning and optimizing the radioactivity at which the seeds are ordered [17], and the shipping frequency minimizes both the patient breast dose and the number of discarded seeds due to insufficient activity. A balanced approach requires using seeds with sufficient activity for adequate localization precision while maintaining radiation doses as low as reasonably achievable (ALARA). In the history of our RSL program, the quantity of RAM used in the RSL seeds, although initially ordered at 4.6 MBq (0.125 mCi) in the program's first year, has been intentionally reduced over the years while maintaining the ability to detect and distinguish the RSL location with the intraoperative probe. In keeping with ALARA principles, this activity was eventually decreased to 3.7 MBq (0.100 mCi) over the next two years and ultimately to 2.8 MBq (0.075 mCi) from mid-2013 through 2021.

Apparent and actual activity are two terms often used to describe the radioactivity of RSL seeds. Actual activity, also known as true activity, represents the intrinsic radioactivity of the radioactive seed, which is characterized by the total number of disintegrations per second. This value is independent of construction material, thickness and other external factors, solely depending on the physical quantity of the radionuclide and its half-life. Actual activity is typically used for calibration purposes, quality control, and ensuring that the radioactive seeds used in the localization procedure meet regulatory standards.

On the other hand, apparent activity refers to the measured activity of the radioactive seed as detected by a gamma camera or probe. This value is lower than the actual activity as it accounts for the attenuation in the titanium shell shielding of the seed and is a standard factor of 1.67 smaller than the actual activity. It serves as a practical parameter for clinicians to localize the seed during the procedure and estimate the radiation dose received by the patient.

RSL activity reductions were possible because of an increased familiarity with the reliability of the probes and the detectability of RSL seeds. Although their initial radiation levels were relatively low, further reductions were technically feasible and appropriate. The effort to optimize seed activity diminishes the radiation exposure to the patient and the staff involved in seed handling, implantation excision and disposal. The lowest activity seed removed by the surgical team had an apparent activity of 0.19 MBq (0.005 mCi) at removal and a total implantation time of 208 d.

2.4. Duration of implant

RSL affords patients a significant degree of flexibility when scheduling implants and explants. A day-of-the-week schedule analysis of RSL appointment data reveals specific patterns suggesting that patient and healthcare professional scheduling preferences align with a traditional U.S. workweek. Based on scheduling data, it has been observed that patients typically choose to have a one-day gap between implantation and surgery, with most procedures occurring from Monday to Thursday. It is noteworthy that Friday implantations leading to Monday surgeries are less frequent. Most (99%) of patients have the seeds excised within 10 d of implantation (figure 2), but on rare occasions, seeds are explanted later. In one outlying case, the seed was successfully excised after as many as 208 d.

Figure 2. Histogram depicting the correlation between the number of implanted radioactive seeds and the duration of seed implantation in the patient's breast tissue. Most patients experience implant durations of 10 d or less, with only 1% outside this range.

Download figure:

Standard image High-resolution image 2.5. Seed implantation by year

Figure 3 displays a significant rise in the number of RSL implants performed per quarter throughout the decade, with wire localizations being replaced mainly by RSL due to its advantages, such as better patient comfort and logistical flexibility. There has been a consistent upward trend of RSL implants annually over the past decade, except for a dip in the second quarter of 2020 due to the COVID-19 pandemic, which caused operational disruptions and reduced elective and non-urgent interventions. However, the number of procedures quickly rebounded, demonstrating the resilience of RSL procedures [27].

Figure 3. Annual trends in Radioactive Seed Localization Implants: A Quarterly Analysis from 2011 to 2023. This histogram depicts the evolution of RSL implant usage over time associated with the rapid replacement of traditional wire localizations. It highlights the marked increase in procedures since the beginning of the program and the impact of the COVID-19 pandemic.

Download figure:

Standard image High-resolution image 2.6. Statistical distribution of seeds per patient

Based on our analysis of the seed distribution per patient, most (74%) patients received only one implanted seed. However, 20% of patients were given two seeds in cases with more extensive lesions. A small percentage of patients required three to six seeds, with 4.81%, 0.83%, 0.15%, and 0.03%, respectively. Nearly all (99%) patients received three or fewer seeds during RSL procedures.

2.7. Usage of implant needles by length

The RSL seeds come preloaded in four lengths of needles: 5 cm, 7 cm, 10 cm, and 15 cm. An example of the needle assembly is shown in figure 1(a). Radiologists generally opt for the shortest needle that can reach the region of interest. Of the more than 25 000 seeds implanted between 2011 and 2021, approximately 92% percent of all implants were performed with the 5 cm or 7 cm needle length, whose usage frequencies were 57% and 35%, respectively. Another 7% were performed with the 10 cm length, with less than 1% of all implants using the 15 cm needle. The RSL seeds have a manufacturer recommendation to be used within the first 90 d after receipt. This recommendation resulted in 83% of the pre-ordered 15 cm needles going unused and discarded (placed into decay-in-storage). Despite their relatively low usage, some must always be available in the event of an unusually deep lesion in a large breast. It is recommended to assess the usage of needle sizes to maintain sufficient inventory while minimizing waste. Because of the 90 day shelf-life of the seeds, this may be accomplished by increasing order frequency and decreasing order quantity rather than maintaining a large, high-activity inventory on site.

2.8. Radiation doses to the patient's breast2.8.1. Breast dosimetry TG43 methodology

The radiation dose to breast tissue associated with RSL procedures was calculated for each seed based on the implanted seed activity, duration of implant and a voxel-based dose rate model. The calculations were performed through two MATLAB routines, with the first routine generating a calculation volume of a hemisphere of 250 cm3 divided into 0.1 cm3 voxels for detailed dose calculation. The simulated position of a single I-125 seed inside the breast varied from the surface (depth = 0 cm) to the radius of the hemisphere (depth = 4.9 cm) in 0.1 cm increments, with approach angles for the seed ranging from 0 to 180 degrees in 5-degree increments.

The second MATLAB routine calculated the dose to each voxel in the breast for each seed position scenario using TG43 [28] with guidance from the American Association of Physicists in Medicine (AAPM), which assumes the medium to be water. The breast doses are calculated as a function of the seed's air-kerma strength U (where 1 U =1 cGy cm2 h−1) [29]. The results were compiled to create dose tables providing the mean dose to the breast in cGy/(U*hour) for a 1 hour seed placement at various depths from the breast surface. These values, shown in figure 4, were obtained by averaging the mean dose for each seed depth over all calculated insertion angles. An additional table to adjust for an arbitrary number of hours of seed placement, considering the seed strength decay, was also generated. The results were verified by comparison with the mean dose predicted by a commercial planning system (BrachyVision, Varian Medical Systems, Paola Alto, CA).

Figure 4. The relationship between dose rate with seed implant depth (0–5 cm) during radioactive seed localization procedures. The graph was constructed under the assumption of a total breast mass of 500 g (two breasts) using the TG43 protocol and was averaged over all seed insertion angles.

Download figure:

Standard image High-resolution image

For each patient, the irradiation time (i.e. the number of hours the seed was implanted in tissue) was approximated, and the mean dose to the breast was calculated by multiplying the corresponding mean dose table lookup with both the relevant time-multiplier table-lookup value, and the seed source strength for the particular patient (apparent activity of the seed at the time of implantation, with conversion factor '1.27 U/mCi' [30]. The exact duration of the implantation was not directly available from the surgical records. However, as a conservative estimate, 6 h was assumed if the implant/explant occurred on the same day. A subject matter expert estimated the same-day implant duration (incision to excision) as 2–3 h based on limited anecdotal evidence. Otherwise, if the two procedures occurred on different days, the seed implant duration was assumed to be the appropriate multiple of 24 h. In calculating the dose to the breast, the ICRP Publication 89 value of 500 g for two breasts was assumed for reference adult females [31].

Figure 4 displays the relationship between the seed implant depth and the radiation dose rate using the second MATLAB routine. It is observed that the dose rate increases up to approximately 2.8 cm, where it begins to decrease similarly with subsequent increases in implant depth.

This approach to calculating the dose for the RSL can be considered conservative as it accounts for the dose to the excised volume of tissue receiving the highest dose as it is closest to the seed. Notably, the dose reported is intended for the remaining healthy breast tissue after removing the lesion, which further emphasizes the conservative nature of this methodology. Lastly, figure 5 indicates that most patients were exposed to 0.1 cGy or less radiation. Because of the conservative nature of the calculations and the low calculated doses, it can be concluded that RSL poses negligible radiological risk to the patients.

Figure 5. A histogram of breast doses for all patients in the study. These values were calculated based on the estimated duration of implant and the seed's I-125 apparent activity, showing the variation in the dose distribution across the RSL patient population. These doses are overestimates because of inherent conservatism in the methodology, as the excised volume has not been deducted from the calculation.

Download figure:

Standard image High-resolution image 2.8.2. Breast dose MIRD methodology

Breast doses from RSL were validated using a secondary approach developed by MIRD [32, 33]. In this approach, the physical half-life of I-125, denoted as Tp, was considered to be 59.4 d (5.13 × 106 s). The mass of the adult female breast was 0.203 kg, and the breast itself was modeled as a unit-density ellipsoid with a specific axes ratio, serving as a geometric representation of the tissue [32]. The energy emitted per decay from I-125's most abundant photon emissions was used, specifically within the 27–31 keV energy range. The absorbed fraction, denoted as ϕBreast←Seed, is the proportion of energy absorbed by the breast tissue for a central point source of I-125 in a unit-density ellipsoid of the same mass and axes ratio as the modeled breast. The dose contribution from particulate radiations (i.e. electrons) from an I-125 brachytherapy seed in the breast is generally negligible due to attenuation in the titanium wall of the seed (actual activity). Thirdly, the cumulative mean absorbed dose to the whole adult female breast, DBreast←Seed(t), up to a given time t post-implantation, per unit activity from a centrally located Iodine-125 brachytherapy seed is calculated. Lastly, this calculation is performed via an exponential decay function, which accounts for the radioactivity decay.

2.8.3. Patient breast dose results

The mean dose to the breast, as calculated using the TG43 methodology, was found to be 0.31 cGy. The 5th and 95th percentile values were 0.04 cGy and 1.00 cGy, respectively. The standard deviation of the dose distribution was 0.42 cGy, and the median value was 0.16 cGy. These results demonstrate the range and variability in the dose distribution across the RSL patient population, as shown in figure 5. It is important to note that these doses are overestimates due to the conservative nature of the methodology, as the dose to the excised volume has not been deducted from the calculation. The magnitude of the overestimate depends on the excised volume, which is typically spheroid with a diameter ranging from 2 cm to 8 cm with an average of 3.5 cm [20]. For comparison, Gennaro et al report that the mean glandular dose for digital mammography and breast tomosynthesis are 0.14 cGy and 0.19 cGy, respectively [34].

2.8.4. Differences between the MIRD and TG43 methodology

The TG43 and MIRD methodology both aim to accurately estimate the breast dose associated with the implantation of a RSL seed. There are several similarities including the consideration of I-125 as the radionuclide source term, the consideration of seed implant duration and the healthy breast tissue as the target of interest for which dose is evaluated. However, the methods differ in several important ways including the assumptions of the seed implant depth distribution, the elemental composition of the attenuating medium and calculational geometry (voxel vs mathematical).

In light of these differences, a consistent difference was noted between the two methods employed for breast dose calculations in RSL procedures. The TG43 method with MATLAB simulations compared to the MIRD methodology yielded different dose estimates. Notably, the MIRD method resulted in a x1.69 increase in breast dose estimation compared to the TG43-based method. Both methods yield conservatively high doses because they include the dose contribution to the excised tissue. That is, the actual dose to the breast tissue should be lower than the values estimated in this paper. While the less precise MIRD methodology gave a higher dose estimate, it is important to note that even these larger values represent very low overall radiation exposures to breast tissue. These findings also reinforce the need for continued research in developing, selecting and implementing dose calculation methodologies in RSL procedures [35].

2.8.5. Radiation dose rates to staff and caregivers

The radiation dose rates to the patients were recorded for two distances: 'on contact dose rates' and '1 meter dose rates'. Both rates were measured across a diverse range of patients, as shown in figure 6. The 'On Contact' dose rates exhibited a more expansive range, extending from 1.38 µSv h −1 to 16.80 µSv h−1, with a median value of 5.50 µSv h−1 . The distribution of these dose rates across patients indicates varying radiation exposure rates, contingent on individual patient body morphologies. As expected, the measured dose rates at 1 m were much lower than their on-contact counterparts, with a range of 0.07 µSv h−1 to 0.91 µSv h−1 (5th to 95th percentile), with a median value of 0.19 µSv h−1 . Note that the dose rates reported in this work are generally those taken directly from ionization dose rate meters where the background readings have not been subtracted. As reported previously, extremity doses are substantially below the regulatory reporting threshold [4]. This analysis suggests that overall dose rates from RSL seeds are relatively low, thereby not significantly increasing the risk level to caregivers and family once implanted in the patient [35, 36]. Most measurements were taken with Fluke 451P and Ludlum 9DP detectors [37, 38].

Figure 6. Comparative Histograms of Radiation Dose Rates at On-Contact and 1 Meter Distances. The lower panel presents the distribution of on-contact radiation dose rates across patients. The upper panel illustrates the distribution of 1 meter radiation dose rates. Note the difference in scale between the two panels. The histograms reveal the range and frequency of radiation dose rates, illustrating the relatively low exposure levels regardless of distance.

Download figure:

Standard image High-resolution image 2.8.6. Implants by indication

Presurgical localization in the breast may be performed for patients with selected indications including, but not limited to, (1) biopsy-proven cancer, (2) biopsy-proven metastatic lymphadenopathy, (3) high-risk lesions diagnosed at percutaneous biopsy, (4) imaging-pathological discordance at core-needle biopsy and (5) cases in which core-needle biopsy is not an option or fails to provide a definitive histological diagnosis [39]. Figure 7 shows the distribution of RSL use across diverse types of breast lesions over the study period. The lesion types are categorized as Ductal Carcinoma in Situ (DCIS) [40], Invasive carcinoma [41], Not Available, and Other (mostly benign breast disease [42]). Over the 11 year period, the highest utilization of RSL was seen in cases of invasive lesions, with proportions as high as approximately 67% in 2019. This shows a relatively stable in the types of RSL indications over time. For DCIS, RSL use fluctuated over the period, with the highest reported use of approximately 21% in 2012 and 2013 and the lowest of around 14% in 2021 [2].

Figure 7. Distribution of radioactive seed localization use in patients across different types of breast lesions from 2011 to 2021.

Download figure:

Standard image High-resolution image 2.8.7. Changes in localization methodology over time

Table 1 summarizes the changing localization techniques used over the past decade. Wire localization, which was the prevalent technique in 2011, constituting 95% of the procedures, experienced a drastic reduction in usage by 2012. This decrease coincided with a substantial increase in the application of mammography RSL, which rose from 4% in 2011 to 73% in 2012, and a minor growth in ultrasound RSL, which increased from 0.3% in 2011 to 5.1% in 2012. The subsequent years showed a persistent decline in Wire Localization utilization, declining to 0.5% by 2021. Conversely, mammography RSL peaked in 2014 at 91%, and ultrasound RSL increased to 22.6% by 2021

Table 1. Trends in the use of different localization techniques from 2010 to 2021. The table shows the percentages of total study procedures utilizing wire localization, mammography-guided RSL, Ultrasound RSL, and MRI RSL. The data illustrates the steady decrease in the use of Wire Localization and the corresponding increase in the use of varying RSL techniques over the study period.

YearWire LocalizationMammography RSLUltrasound RSLMRI RSL*2010100%   201195%4%0.3% 201222%73%5.1% 201314%81%5.0% 20144%91%5.0% 20154%89%6.1% 20163%91%6.1% 20173%85%11.7% 20182%84%13.8% 20192%84%14.5%0.2%20201%80%18.4%0.5%20210.5%77%22.6%0.4%

*RSL under MRI still involves either mammography or ultrasound.

Excision of lesions visible only by MRI accounted for 0.2%–0.5% of cases between 2019 and 2020. Notably, MRI RSL incorporates mammography or ultrasound RSL. The MRI is utilized to visualize the lesion and implant a marker for the subsequent placement of the seed under mammography/ultrasound guidance. At present, wire localization is reserved for cases of re-excision requiring localization for residual calcifications to avoid the risk of seeds floating in the lumpectomy cavity or when large hematomas from core biopsy are present.

3.1. Presurgical considerations

RSL implants provide providers and patients the most flexibility to schedule their lumpectomies relative to other localization methods [4]. While wire localization usually occurs on the same day as the surgery, RSL implants remain implanted for an average of 2 d. Prior to RSL implantation the patient should be medically cleared for surgery and the diagnostic imaging workup completed. For biopsies performed elsewhere, surgical pathology should confirm the diagnosis internally before scheduling an RSL implant.

Most explants do not occur on the same day of the surgery so it is prudent to determine the ability of the patient to comply with precautions. These include not holding babies for any longer than 30 min per day and following the surgeon's instructions regarding showering after the procedure. In addition, seeds are only implanted in patients who are likely to return for the explantation procedure. There are also physiological reasons why a patient may not be fit for an RSL implant. For example, if the patient presents with a hematoma [3], then the seed will simply drop into the liquid volume. In these cases, wire localizations are still used. There have also been patients hesitant to receive the implant due to a concern about a reaction to the iodine in the seed or a concern about the radiation risk. However, these seeds are sealed sources, and there is no direct contact with iodine. Leaks from the seed are unlikely when appropriate medical precautions such as avoiding the use of scissors and not holding the seed firmly with tweezers while still cutting tissue are followed [20, 43, 44].

Certain patients are not well-suited for RSL implantation. Patients who are pregnant are not candidates for RSL, and patients under the age of 18 with non-palpable lesions, while rare, receive wire localization due to concern for radiation exposure in the developing breast. Breastfeeding women are advised to consider different forms of localization if they wish to continue breastfeeding.

Several RSL implants in a breast may be placed due to the presence of multiple discreet lesions or sites to bracket an area of more extensive disease. If the lesion is large enough, the radiologist may choose to bracket the lesion with seeds. In these cases, the seeds are not implanted within the volume of interest, but rather near the boundaries of the lesion. In general, seeds closer together than 2 cm cannot be separately identified intraoperatively.

3.2. Surgical considerations

Finding the location of the RSL implanted seed during surgery was not reported to be an issue. Over the course of the program, we have gradually reduced the ordered activity of the RSL seeds. The initial apparent activity of the seeds has stepped down from 4.6 MBq to 3.7 MBq to 2.8 MBq (125 uCi, to 100 uCi, to 75 uCi). These seeds can be used up to 90 d after ordering and have routinely been implanted over a full half-life from their initial activity when ordered. We currently use the Mamotome Neoprobe for surgical radio guidance. These probes have proven to be reliable and simple to use. They can be calibrated Energy windows on the probes can be set for I-125 or Tc99m to exclusively identify the isotope of interest. Although the radioactive seeds are constructed with a titanium shell, caution should be exercised if using surgical scissors for the excision as they can (may) pierce the shell and potentially cause a leakage of RAM. The surgeon uses the Neoprobe to confirm there are no seeds left in the patient at the end of the procedure. The specimen and seed(s) are placed on a board for radiographic imaging (in a cabinet x-ray unit) to visually confirm the removal of the seed. Excision of the seed is documented on the specimen radiograph and entered into a tracking database in the operating room.

3.3. Post-surgical considerations

All explanted RSL seeds are sent to the pathology department for removal from the excised tissue specimen. It is important to note that these seeds cannot be treated like other medical waste and must be continually tracked as licensed RAM. To prevent a reportable regulatory event [10CFR20.2201] associated with the loss of RAM, pathology assistants confirm the placement of the seed into a specimen bag with appropriate radiation detection equipment. This can be a GM, LEG, or Gamma Probe. The purpose is to ensure the item placed into the specimen bag is the seed and not a clip or flake of pathology ink. They then update the RSL inventory database and physically sign the bag containing the seed.

3.4. Health physics considerations

One of the unique demands of an RSL program is the constant need to account for the RAM across the institutional usage life from ordering, receiving, implanting, explanting, and ultimately discarding as radioactive waste. Unlike in wire localization, where the wires become medical waste, RSL seeds are still licensed RAM that needs to be controlled and inventoried after explant. We use a dedicated software database, internally built, which tracks the seeds from cradle to grave. An intranet-based RSL inventory log acting as the dedicated database tracked information on each part of the journey: seed receipt, initial inventory, storage, implant, surgical excision, pathology explant and ultimate decay-in-storage. Institutional staff members from relevant departments (e.g. from radiation safety, medical physics, radiology, surgery, and pathology) were able to access and update inventory information at each interaction point of the overall RSL process [4]

As the RSL program matured, additional capabilities were added to the database tracking system. At the program's inception, all implants and explants took place in the same building under a single regulatory body. At present, radiologists implant seeds at six clinical locations under the regulatory oversight of three distinct regulatory bodies. Furthermore, seed explant procedures are conducted at three of these locations. To properly track and satisfy regulatory information requests, it became necessary to modify the database to allow for appropriate RAM inventories at each location to be kept, reflecting seed delivery/implantation and seed explantation, pathology evaluation, and ultimate disposal.

Initially, it was relatively uncommon for any patient to receive more than one seed. However, as the program matured, clinicians became increasingly comfortable using the seeds, and breast conservation treatment for breast cancer became more prevalent, so multiple seed implants, either unilateral or bilateral, have become commonplace. This posed a new risk as surgeons could potentially fail to excise all implanted seeds. Each seed has a unique database record, and there was initially no indication of the presence of multiple seeds in that entry. Therefore, to minimize the possibility of a seed accidentally being left in a patient, we added a field for the total number of seeds in the patient; if a patient were to have three seeds implanted, each of the entries would include '3' in this field.

In addition to the RSL database, paper records are maintained locally at the site of the RSL implant until the explant has been performed. Furthermore, all information about the seeds is annotated on post-implantation breast images to make it more readily accessible to the surgeon. The number of seeds present in each breast has also been incorporated into the surgical time-out procedure. These redundancies provide the surgical team with multiple avenues of validation should any questions arise in the operating room.

In all areas in which the seed is handled, whether during implantation, explantation, or post-surgical processing, appropriate radiation detection equipment should be readily available. Because of their small size, seeds can easily adhere to other tissues or tools during their removal and pathology processing. Minimizing the duration for which a seed may be unaccounted for can ultimately minimize the loss of materials. Additionally, it is best practice to check the implant needle prior to discarding it to ensure there is no false deployment of the seed and no RAM ends up in the sharp disposal containers. Locating and retrieving a lost RSL seed from a large shipment of medical waste can be an unpleasant undertaking, so extra steps are taken to prevent this type of RAM loss.

Although programmatic workflows should prevent the loss of a seed, a seed may still be accidentally misplaced with medical waste from an operating room or from the pathology laboratory. For example, after a seed was successfully removed from a patient, it became inadvertently caught on a piece of gauze and placed in the trash. It was not identified as missing until the pathology laboratory noted the lack of seed in the specimen. By this time, the operating room had already been cleared for the next case. Therefore, it is important to have a waste screening program to prevent the loss of RAMs. Utilizing wall-mounted radiation detection equipment near the waste management area allows environmental services to separate any trash, which sets off the alarms for further investigation.

At the inception of the RSL program, all hospital staff involved in radiology, surgery, and pathology were routinely monitored with NVLAP-accredited radiation dosimeters. Implant radiologists were further monitored with ring dosimeters. Within the first year, the use of the monitoring rings was stopped as no employees showed any radiation exposure above background levels. Additionally, after several years of monitoring, the practice of personnel radiation monitoring for surgeons and pathologists based on their involvement in the RSL program was stopped. Since well over 95% of the recorded results were below the annual dose recording threshold of'10 mrem' (0.1 mSv) [45], it was concluded that despite the large volume of implanted I-125 seeds, the staff radiation was so small that routine radiation monitoring was unnecessary.

3.5. Reporting, licensing and regulatory considerations

As with any invasive medical procedure, RSL implantation and explanation involves a degree of risk that is discussed in advance with the patient as part of informed consent. From a radiation safety perspective, the risks associated with an RSL program include medical events reportable under 10 CFR 35.3045, the risk of seed being damaged during surgery or dissection, the loss of a seed, and the patient being unable or unwilling to return for surgery post-implantation. Under 35.3045, a medical event involving an RSL seed would be reportable to the NRC or agreement state if the implantation of an RSL seed (a) involved the wrong radionuclide, (b) was implanted in the wrong patient, (c) the wrong number of seeds were implanted; or (d) the licensee did not perform an explantation surgery and the implanted RSL seed(s) resulted in a dose that exceeds 0.05 Sv (5 rem) effective dose equivalent or 0.5 Sv (50 rem) to an organ or tissue [46]. Events involving the wrong radionuclide, wrong patient, and/or wrong number of seeds can be pre-empted by proper patient identification and RSL seed inventory. As for the risk of a seed being damaged during surgery or dissection, the use of proper instrumentation mitigates this, as the scalpels used are unlikely to damage the seed [44]. Before using a cryostat or microtome, the pathologist must verify that the seed is no longer in the specimen [47]. Due to their size, the most likely reportable event involving an RSL seed is the loss of RAM under 10 CFR 22.2201, as licensed material greater than ten times the amount in Part 20, Appendix C (1uCi for I-125). Extensive surveys are performed in the event of a potentially lost seed and are almost always successful.

Since 2013, the RSL program has reported seven instances in which an RSL seed could not be located and was reported in a timely manner to the pertinent corresponding regulator. These incidents largely fall into two categories: (1) seeds that are lost post-explantation and presumed to be washed down the drain or disposed of with the hospital's solid waste, and (2) surface-implanted seeds that are lost in the patient's home and are presumed to have been washed down the drain or disposed of with the household trash. These seeds are formally determined to be lost in a patient's home when they cannot be verified radiographically or with handheld radiation-detecting instrumentation. In such a scenario, the patient may have to return for the implantation of one or more additional RSL seeds. Patient education material has been updated to explicitly advise patients against removing the applied Steristrip sterile bandages post-implantation, even while showering, to visually inspect loose bandages for seeds.

Post-explantation, the RSL seeds are identified in the removed specimen and ultimately placed in storage. During this period, seeds may adhere to or be covered by tissue or fluid. On several occasions, seeds could not be found in the pathology department using portable radiation-detecting equipment and were presumed to have been washed down the drain or disposed of with solid waste. The methods to prevent such occurrences include the use of a radiation meter to confirm that removed seeds are indeed RSL seeds and not part of a clip or some other non-RAM and verification from two individuals to confirm that the seed is placed into storage. Additionally, the use of a corded Geiger Müller meter is recommended to ensure a radiation meter is always available and operable.

On rare occasions, patients may be unable or unwilling to return for surgery and the explantation of RSL seeds. When notified that a patient is not returning, the Medical Health Physics department makes a specific note, supplementing the clinician's documentation in the EMR.

A retrospective analysis of a high-volume cancer center's RSL program has shown that it is a safe and effective method for breast surgery. This study demonstrates the importance of radiation protection fundamentals for a successful application of RSL. The quantity of RAM in RSL seeds has been optimized over time, decreasing from 4.6 MBq to 2.8 MBq to reduce radiation exposure per ALARA principles. The typical duration of seed implantation has been minimized to 1–2 d, with 99% of seeds explanted within 10 d. Over the course of the study, Invasive carcinoma was the most common indication at 67% of RSL cases, while DCIS utilization fluctuated between 14%–21%. Mammography-guided RSL rose from 4% to 77%, while wire localization fell from 95% to 0.5% during 2011–2021. The radiation dose to the breast tissue from RSL is very low, with 95% of patients receiving ⩽1 cGy to the breast tissue. Seeds must be tracked from ordering to explant as licensed RAM and seven lost seed incidents have been reported since 2013, largely attributed to post-explant loss, emphasizing the importance of patient education on not disturbing implant sites before surgery.

It is crucial for institutions to establish seamless communication between the implanting radiologist and the explanting surgeon to optimize the localization and excision process. Other institutions that plan to introduce, improve, or expand their RSL programs may benefit from the lessons learned from this review. This includes establishing a comprehensive database or tracking system to monitor the entire process, from seed receipt to disposal, to ensure proper control and management of RAMs. In addition, fostering a culture of optimization and continuous improvement is important to minimize radiation exposure for patients and medical staff. This can involve reducing the ordered activity of RSL seeds over time, as well as regularly reviewing and updating protocols and procedures to enhance safety and efficiency. Furthermore, patient preferences and schedu