Prostate-specific membrane antigen radioguided surgery with negative histopathology: an in-depth analysis.

PURPOSE: To identify reasons for negative histopathology of specimens from prostate-specific membrane antigen (PSMA) radioguided surgery (PSMA-RGS) in recurrent prostate cancer (PCa) after prostatectomy. METHODS: Of 302 patients who underwent PSMA-RGS, 17 (5.6%) demonstrated a negative histopathology. Preoperative data, PSMA PET, PSMA SPECT, and follow-up information were analyzed retrospectively to differentiate true/false positive (TP/FP) from true/false negative (TN/FN) lesions. RESULTS: The median prostate-specific antigen at PET was 0.4 ng/ml (interquartile range [IQR] 0.3-1.2). Twenty-five index lesions (median short axis 7 mm, IQR 5-8; median long-axis 12 mm, IQR 8-17) had a median SUVmax of 4 (IQR 2.6-6; median PSMA expression score 1, IQR 1-1). Six lesions were TP, twelve were FP, one was TN, and six remained unclear. All TP lesions were in the prostatic fossa or adjacent to the internal iliac arteries. Three suspected local recurrences were FP. All FP lymph nodes were located at the distal external iliac arteries or outside the pelvis. A low PSMA-expressing TN node was identified next to a common iliac artery. Unclear lesions were located next to the external iliac arteries or outside the pelvis. CONCLUSION: In most cases with a negative histopathology from PSMA-RGS, lesions were FP on PSMA PET. Unspecific uptake should be considered in low PSMA-expressing lymph nodes at the distal external iliac arteries or outside the pelvis, especially if no PSMA-positive lymph nodes closer to the prostatic fossa are evident. Rarely, true positive metastases were missed by surgery or histopathology.

Steerable DROP-IN radioguidance during minimal-invasive non-robotic cervical and endometrial sentinel lymph node surgery.

PURPOSE: The recently introduced tethered DROP-IN gamma probe has revolutionized the way robotic radioguided surgery is performed, fully exploiting the nature of steerable robotic instruments. Given this success, the current first-in-human study investigates if the DROP-IN can also provide benefit in combination with steerable non-robotic instruments during conventional laparoscopic surgery, showing equivalence or even benefit over a traditional rigid gamma probe. METHODS: The evaluation was performed in ten patients during laparoscopic cervical (n = 4) and endometrial (n = 6) cancer sentinel lymph node (SLN) procedures. Surgical guidance was provided using the hybrid, or bi-modal, SLN tracer ICG-99mTc-nanocolloid. SLN detection was compared between the traditional rigid laparoscopic gamma probe, the combination of a DROP-IN gamma probe and a steerable laparoscopic instrument (LaproFlex), and fluorescence imaging. RESULTS: The gynecologists experienced an enlarged freedom of movement when using the DROP-IN + LaproFlex combination compared to the rigid laparoscopic probe, making it possible to better isolate the SLN signal from background signals. This did not translate into a change in the SLN find rate yet. In both cervical and endometrial cancer combined, the rigid probe and DROP-IN + LaproFlex combination provided an equivalent detection rate of 96%, while fluorescence provided 85%. CONCLUSION: We have successfully demonstrated the in-human use of steerable DROP-IN radioguidance during laparoscopic cervical and endometrial cancer SLN procedures, expanding the utility beyond robotic procedures. Indicating an improved surgical experience, these findings encourage further investigation and consideration on a path towards routine clinical practice and improved patient outcome. TRIAL REGISTRATION: HCB/2021/0777 and NCT04492995; https://clinicaltrials.gov/study/NCT04492995.

First-in-human validation of a DROP-IN ß-probe for robotic radioguided surgery: defining optimal signal-to-background discrimination algorithm.

PURPOSE: In radioguided surgery (RGS), radiopharmaceuticals are used to generate preoperative roadmaps (e.g., PET/CT) and to facilitate intraoperative tracing of tracer avid lesions. Within RGS, there is a push toward the use of receptor-targeted radiopharmaceuticals, a trend that also has to align with the surgical move toward minimal invasive robotic surgery. Building on our initial ex vivo evaluation, this study investigates the clinical translation of a DROP-IN ß probe in robotic PSMA-guided prostate cancer surgery. METHODS: A clinical-grade DROP-IN ß probe was developed to support the detection of PET radioisotopes (e.g., 68 Ga). The prototype was evaluated in 7 primary prostate cancer patients, having at least 1 lymph node metastases visible on PSMA-PET. Patients were scheduled for radical prostatectomy combined with extended pelvic lymph node dissection. At the beginning of surgery, patients were injected with 1.1 MBq/kg of [68Ga]Ga-PSMA. The ß probe was used to trace PSMA-expressing lymph nodes in vivo. To support intraoperative decision-making, a statistical software algorithm was defined and optimized on this dataset to help the surgeon discriminate between probe signals coming from tumors and healthy tissue. RESULTS: The DROP-IN ß probe helped provide the surgeon with autonomous and highly maneuverable tracer detection. A total of 66 samples (i.e., lymph node specimens) were analyzed in vivo, of which 31 (47%) were found to be malignant. After optimization of the signal cutoff algorithm, we found a probe detection rate of 78% of the PSMA-PET-positive samples, a sensitivity of 76%, and a specificity of 93%, as compared to pathologic evaluation. CONCLUSION: This study shows the first-in-human use of a DROP-IN ß probe, supporting the integration of ß radio guidance and robotic surgery. The achieved competitive sensitivity and specificity help open the world of robotic RGS to a whole new range of radiopharmaceuticals.

Defining the optimal target-to-background ratio to identify positive lymph nodes in prostate cancer patients undergoing robot-assisted [99mTc]Tc-PSMA radioguided surgery: updated results and ad interim analyses of a prospective phase II study.

INTRODUCTION: Prostate-specific membrane antigen radioguided surgery (PSMA-RGS) might identify lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing extended pelvic lymph node dissection (ePLND). The optimal target-to-background (TtB) ratio to define RGS positivity is still unknown. MATERIALS & METHODS: Ad interim analyses which focused on 30 patients with available pathological information were conducted. All patients underwent preoperative PSMA positron emission tomography (PET). 99m-Technetium-PSMA imaging and surgery ([99mTc]Tc-PSMA-I&S) was administered the day before surgery. In vivo measurements were conducted using an intraoperative gamma probe. Performance characteristics and implications associated with different TtB ratios were assessed. RESULTS: Overall, 9 (30%) patients had LNI, with 22 (13%) and 80 (11%) positive regions and lymph nodes, respectively. PSMA-RGS showed uptakes in 12 (40%) vs. 7 (23%) vs. 6 (20%) patients for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4. At a per-region level, sensitivity, specificity and accuracy for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4 were 72%, 88% and 87% vs. 54%, 98% and 92% vs. 36%, 99% and 91%. Performing ePLND only in patients with suspicious spots at PSMA PET (n = 7) would have spared 77% ePLNDs at the cost of missing 13% (n = 3) pN1 patients. A TtB ratio ≥ 2 at RGS identified 8 (24%) suspicious areas not detected by PSMA PET, of these 5 (63%) harbored LNI, with one pN1 patient (11%) that would have been missed by PSMA PET. Adoption of a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4, would have allowed to spare 18 (60%) vs. 23 (77%) vs. 24 (80%) ePLNDs missing 2 (11%) vs. 3 (13%) vs. 4 (17%) pN1 patients. CONCLUSIONS: PSMA-RGS using a TtB ratio ≥ 2 to identify suspicious nodes, could allow to spare > 50% ePLNDs and would identify additional pN1 patients compared to PSMA PET and higher TtB ratios.

99mTcPSMA-radioguided surgery in oligorecurrent prostate cancer: the randomised TRACE-II trial.

OBJECTIVE: To investigate whether combination treatment of prostate-specific membrane antigen (PSMA)-based radioguided surgery (RGS) with short-term androgen deprivation therapy (ADT) improves oncological outcomes in men with oligorecurrent prostate cancer (PCa) as compared to treatment with short-term ADT only. METHODS: The TRACE-II study is an investigator-initiated, prospective, randomised controlled clinical trial. Patients (aged >18 years) with hormone-sensitive recurrent PCa after radical prostatectomy or radiotherapy (brachytherapy or external beam radiotherapy), with involvement of ≤2 lymph nodes or local oligorecurrent disease within the pelvis as determined by PSMA positron emission tomography (PET)/computed tomography (CT) are randomly assigned in a 1:1 ratio between 6-month ADT (Arm A) or 6-month ADT plus RGS (Arm B). The primary objective is to determine clinical progression-free survival (CPFS) at 24 months. After PSMA-RGS, CPFS is defined as the time between the start of treatment and the appearance of a re-recurrence (any N1 or M1) as suggested by PSMA-PET/CT or symptoms related to progressive PCa, or death from any cause. The secondary objectives include metastasis-free survival at 2, 5 and 10 years, biochemical progression-free survival at 2 years, and patient-reported quality of life at 2, 5 and 10 years. A total of 60 patients, 30 per arm, will be included. The trial is powered (80%) to detect at least a 30% absolute difference in CPFS between the two study arms in the period 2 years after randomisation. We expect to enrol the required participants in 3 years. The study has an expected duration of 5 years in total. CONCLUSIONS: Combining RGS with short-term ADT might be oncologically beneficial for patients with oligorecurrent PCa. In this first randomised controlled trial, we are investigating the potential oncological benefits of this combined treatment, while also focusing on maintaining quality of life.

Imaging adjuvants in pediatric surgical oncology.

Surgery is a crucial component of pediatric cancer treatment, but conventional methods may lack precision. Image-guided surgery, including fluorescent and radioguided techniques, offers promise for enhancing tumor localization and facilitating precise resection. Intraoperative molecular imaging utilizes agents like indocyanine green to direct surgeons to occult deposits of tumor and to delineate tumor margins. Next-generation agents target tumors directly to improve specificity. Radioguided surgery, employing tracers like metaiodobenzylguanidine (MIBG), complements fluorescent techniques by allowing for detection of tumors at a greater depth. Dual-labeled agents combining both modalities are under development. Three-dimensional modeling and virtual/augmented reality aid in preoperative planning and intraoperative guidance. The above techniques show great promise to benefit patients with pediatric tumors, and their continued development will almost certainly improve surgical outcomes.

Comparative analysis of robot-assisted and open approach for PSMA-radioguided surgery in recurrent prostate cancer.

PURPOSE: To compare the oncological and surgical outcomes of patients with recurrent prostate cancer (PCa) who underwent either open or newly established robot-assisted salvage prostate-specific membrane antigen-radioguided surgery (PSMA-RGS). MATERIALS AND METHODS: Patients who consecutively underwent PSMA-RGS for PCa recurrence between January 2021 and December 2022 were identified. The rate of complete biochemical response, biochemical recurrence-free survival [BFS], and the rate of salvage therapy were evaluated. Univariable and multivariable regression models tested the association between the surgical approach and surgical outcomes. RESULTS: Overall, 85 patients were selected, with 61 patients (72%) undergoing open PSMA-RGS and 24 patients (28%) receiving a robot-assisted approach. The oncological outcomes of the two groups were comparable (12-month BFS: 41% (Confidence interval (CI): 29-58%) vs. 39% (CI: 19-79%), p = 0.9, respectively). According to multivariable regression models, the robotic approach did not significantly influence estimated blood loss (EBL) (ß = -40, 95% CI: -103, 22; p = 0.2) and significantly increased operative time (OT) (ß = 28, 95% CI: 10, 46; p = 0.002). No Clavien-Dindo III-V complications were reported in the robotic group. CONCLUSION: Both, the open as well as the robot-assisted approach for PSMA-RGS had comparable oncological outcomes. No safety concerns arose for the robotic-assisted approach offering a potentially improved quality of life for patients.

Delphi consensus project on prostate-specific membrane antigen (PSMA)-targeted surgery-outcomes from an international multidisciplinary panel.

PURPOSE: Prostate-specific membrane antigen (PSMA) is increasingly considered as a molecular target to achieve precision surgery for prostate cancer. A Delphi consensus was conducted to explore expert views in this emerging field and to identify knowledge and evidence gaps as well as unmet research needs that may help change practice and improve oncological outcomes for patients. METHODS: One hundred and five statements (scored by a 9-point Likert scale) were distributed through SurveyMonkey®. Following evaluation, a consecutive second round was performed to evaluate consensus (16 statements; 89% response rate). Consensus was defined using the disagreement index, assessed by the research and development project/University of California, Los Angeles appropriateness method. RESULTS: Eighty-six panel participants (72.1% clinician, 8.1% industry, 15.1% scientists, and 4.7% other) participated, most with a urological background (57.0%), followed by nuclear medicine (22.1%). Consensus was obtained on the following: (1) The diagnostic PSMA-ligand PET/CT should ideally be taken < 1 month before surgery, 1-3 months is acceptable; (2) a 16-20-h interval between injection of the tracer and surgery seems to be preferred; (3) PSMA targeting is most valuable for identification of nodal metastases; (4) gamma, fluorescence, and hybrid imaging are the preferred guidance technologies; and (5) randomized controlled clinical trials are required to define oncological value. Regarding surgical margin assessment, the view on the value of PSMA-targeted surgery was neutral or inconclusive. A high rate of "cannot answer" responses indicates further study is necessary to address knowledge gaps (e.g., Cerenkov or beta-emissions). CONCLUSIONS: This Delphi consensus provides guidance for clinicians and researchers that implement or develop PSMA-targeted surgery technologies. Ultimately, however, the consensus should be backed by randomized clinical trial data before it may be implemented within the guidelines.

Role of a portable gamma-camera with optical view for margins assessment of pulmonary nodules resected by radioguided surgery.

PURPOSE: Radioguided occult lesion localization (ROLL) of pulmonary nodules is an alternative to hook-wire. Both required of a histological margin assessment. The activity emerging from the radiotracer allows to obtain an intraoperative scintigraphic image of the surgical specimen by a portable gamma-camera (PGC) fitted with an optical view, which provides information about the localization of the nodule in relation to the margins. The aim of this study was to evaluate the intraoperative use of a PGC for margin assessment of pulmonary nodules. METHODS: ROLL technique was used in 38 nodules (36 pulmonary, 1 chest wall, and 1 pleural nodules). A PGC intraoperative image of the surgical specimen was obtained in 32. Scintigraphic results were compared to the histological assessment. Other factors, such as nodule size, distance from the pleural surface, or distance covered by the needle, were considered as possible factors for non-centered lesions. RESULTS: PGC images showed that the lesion was in contact with the margins in 8/32 cases and centered in 24. In all cases in which the lesion was considered as centered by the PGC, the margins were free of involvement (NPV 100%), although the PPV is low. CONCLUSIONS: The use of a PGC for margin assessment after pulmonary nodule resection is feasible and provides a high NPV in our series. In addition, the short intraoperative time required for its use makes the PGC a useful tool for providing supplementary information to histopathologic results. Further studies from different surgical teams are required for an external validation.

The Click-On gamma probe, a second-generation tethered robotic gamma probe that improves dexterity and surgical decision-making.

PURPOSE: Decision-making and dexterity, features that become increasingly relevant in (robot-assisted) minimally invasive surgery, are considered key components in improving the surgical accuracy. Recently, DROP-IN gamma probes were introduced to facilitate radioguided robotic surgery. We now studied if robotic DROP-IN radioguidance can be further improved using tethered Click-On designs that integrate gamma detection onto the robotic instruments themselves. METHODS: Using computer-assisted drawing software, 3D printing and precision machining, we created a Click-On probe containing two press-fit connections and an additional grasping moiety for a ProGrasp instrument combined with fiducials that could be video tracked using the Firefly laparoscope. Using a dexterity phantom, the duration of the specific tasks and the path traveled could be compared between use of the Click-On or DROP-IN probe. To study the impact on surgical decision-making, we performed a blinded study, in porcine models, wherein surgeons had to identify a hidden 57Co-source using either palpation or Click-On radioguidance. RESULTS: When assembled onto a ProGrasp instrument, while preserving grasping function and rotational freedom, the fully functional prototype could be inserted through a 12-mm trocar. In dexterity assessments, the Click-On provided a 40% reduction in movements compared to the DROP-IN, which converted into a reduction in time, path length, and increase in straightness index. Radioguidance also improved decision-making; task-completion rate increased by 60%, procedural time was reduced, and movements became more focused. CONCLUSION: The Click-On gamma probe provides a step toward full integration of radioguidance in minimal invasive surgery. The value of this concept was underlined by its impact on surgical dexterity and decision-making.

A CT-based radiomics model to detect prostate cancer lymph node metastases in PSMA radioguided surgery patients.

PURPOSE: In recurrent prostate carcinoma, determination of the site of recurrence is crucial to guide personalized therapy. In contrast to prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) imaging, computed tomography (CT) has only limited capacity to detect lymph node metastases (LNM). We sought to develop a CT-based radiomic model to predict LNM status using a PSMA radioguided surgery (RGS) cohort with histological confirmation of all suspected lymph nodes (LNs). METHODS: Eighty patients that received RGS for resection of PSMA PET/CT-positive LNMs were analyzed. Forty-seven patients (87 LNs) that received inhouse imaging were used as training cohort. Thirty-three patients (62 LNs) that received external imaging were used as testing cohort. As gold standard, histological confirmation was available for all LNs. After preprocessing, 156 radiomic features analyzing texture, shape, intensity, and local binary patterns (LBP) were extracted. The least absolute shrinkage and selection operator (radiomic models) and logistic regression (conventional parameters) were used for modeling. RESULTS: Texture and shape features were largely correlated to LN volume. A combined radiomic model achieved the best predictive performance with a testing-AUC of 0.95. LBP features showed the highest contribution to model performance. This model significantly outperformed all conventional CT parameters including LN short diameter (AUC 0.84), LN volume (AUC 0.80), and an expert rating (AUC 0.67). In lymph node-specific decision curve analysis, there was a clinical net benefit above LN short diameter. CONCLUSION: The best radiomic model outperformed conventional measures for detection of LNM demonstrating an incremental value of radiomic features.

Robot-assisted laparoscopic surgery using DROP-IN radioguidance: first-in-human translation.

PURPOSE: Radioguided surgery has been widely used for clinical procedures such as sentinel node resections. In the (robot-assisted) laparoscopic setting radioguidance is realized using laparoscopic gamma probes, which have limited maneuverability. To increase the rotational freedom, a tethered DROP-IN gamma probe was designed. Here we present the first in vivo feasibility study of this technology in prostate cancer patients. METHODS: Ten patients scheduled for a sentinel node procedure received four injections into the prostate with (indocyanine green-)99mTechnetium-nanocolloid and underwent preoperative imaging (lymphoscintigraphy and SPECT/CT). The DROP-IN probe was inserted via the assistant port, still permitting the insertion and usage of additional laparoscopic tools. RESULTS: The sentinel nodes were resected using the da Vinci® Si robot under guidance of DROP-IN gamma tracing and fluorescence imaging. The surgeon was able to independently maneuver the DROP-IN probe using the ProGrasp® forceps of the da Vinci® robot and distinguish sentinel nodes from background signal (such as the injection site). CONCLUSIONS: Overall the DROP-IN design proves to be a valuable tool for robot-assisted radioguided surgery approaches.

The EANM practical guidelines for sentinel lymph node localisation in oral cavity squamous cell carcinoma.

PURPOSE: Sentinel lymph node biopsy is an essential staging tool in patients with clinically localized oral cavity squamous cell carcinoma. The harvesting of a sentinel lymph node entails a sequence of procedures with participation of specialists in nuclear medicine, radiology, surgery, and pathology. The aim of this document is to provide guidelines for nuclear medicine physicians performing lymphoscintigraphy for sentinel lymph node detection in patients with early N0 oral cavity squamous cell carcinoma. METHODS: These practice guidelines were written and have been approved by the European Association of Nuclear Medicine (EANM) and the International Atomic Energy Agency (IAEA) to promote high-quality lymphoscintigraphy. The final result has been discussed by distinguished experts from the EANM Oncology Committee, and national nuclear medicine societies. The document has been endorsed by the Society of Nuclear Medicine and Molecular Imaging (SNMMI). These guidelines, together with another two focused on Surgery and Pathology (and published in specialised journals), are part of the synergistic efforts developed in preparation for the "2018 Sentinel Node Biopsy in Head and Neck Consensus Conference". CONCLUSION: The present practice guidelines will help nuclear medicine practitioners play their essential role in providing high-quality lymphatic mapping for the care of early N0 oral cavity squamous cell carcinoma patients.

Performance of 111In-labelled PSMA ligand in patients with nodal metastatic prostate cancer: correlation between tracer uptake and histopathology from lymphadenectomy.

PURPOSE: Intraoperative identification of lymph node (LN) metastases (LNM) detected on preoperative PSMA PET/CT may be facilitated by PSMA radioguided surgery with the use of a gamma probe. We evaluated the uptake of 111In-labelled PSMA ligand DKFZ-617 (referred to as 111In-PSMA-617) in unaffected LN and LNM at the level of single LN. METHODS: Six patients with prostate cancer (PCa) with suspicion of LNM on preoperative PSMA PET/CT underwent 111In-PSMA-617-guided lymphadenectomy (LA; four salvage LA and two primary LA). 111In-PSMA-617 (109 ± 5 MBq). was injected Intravenously 48 h prior to surgery Template LAs were performed in small subregions: common, external, obturator and internal iliac vessels, and presacral and retroperitoneal subregions (n = 4). Samples from each subregion were isolated aiming at the level of single LN. Uptake was measured ex situ using a germanium detector. Receiver operating characteristic (ROC) analysis was performed based on 111In-PSMA-617 uptake expressed as standardized uptake values normalized to lean body mass (SUL). RESULTS: Overall 310 LN (mean 52 ± 19.7) were removed from 74 subregions (mean 12 ± 3.7). Of the 310 LN, 35 turned out to be LNM on histopathology. Separation of the samples from all subregions resulted in 318 single specimens: 182 PCa-negative LN samples with 275 LN, 35 single LNM samples, 3 non-nodal PCa tissue samples and 98 fibrofatty tissue samples. The median SULs of nonaffected LN (0.16) and affected LN (13.2) were significantly different (p < 0.0001). Based on 38 tumour-containing and 182 tumour-free specimens, ROC analysis revealed an area under the curve of 0.976 (95% CI 0.95-1.00, p < 0.0001). Using a SUL cut-off value of 1.136, sensitivity, specificity, positive predictive value, negative predictive value and accuracy in discriminating affected from nonaffected LN were 92.1% (35/38), 98.9% (180/182), 94.6% (35/37), 98.4% (180/183) and 97.7% (215/220), respectively. CONCLUSION: Ex situ analysis at the level of single LN showed that 111In-PSMA-617 had excellent ability to discriminate between affected and nonaffected LN in our patients with PCa. This tracer characteristic is a prerequisite for in vivo real-time measurements during surgery.

Novel technology of molecular radio-guidance for lymph node dissection in recurrent prostate cancer by PSMA-ligands.

PURPOSE: Recently, prostate-specific membrane antigen-radioguided surgery (PSMA-RGS) has been introduced as a promising new and individual treatment concept in patients with localised recurrent prostate cancer (PC). In the following, we want to review our experience with PSMA-RGS in patients with localised biochemical recurrent PC. METHODS: A non-systematic review of the literature was carried out with focus on technical and logistical aspects of PSMA-RGS. Furthermore, published data on intraoperative detection of metastatic lesions compared to preoperative PSMA-PET and postoperative histopathology, postoperative complications as well as oncological follow-up data are summarized. Finally, relevant aspects on prerequisites for PSMA-RGS, patient selection, and the potential benefit of additional salvage radiotherapy or potential future applications of robotic PSMA-RGS with drop-in γ-probes are discussed. RESULTS: First results show that PSMA-RGS is very sensitive and specific in tracking suspicious lesions intraoperatively. Prerequisite for patient selection and localisation of tumour recurrence is a positive Ga-HBED-CC PSMA positron-emission tomography (PET) scan with preferably only singular soft tissue or lymph node recurrence after primary treatment. Furthermore, PSMA-RGS has the potential to positively influence oncological outcome. CONCLUSIONS: PSMA-RGS seems to be of high value in patients with localised PC recurrence for exact localisation and resection of oftentimes small metastatic lesions using intraoperative and ex vivo γ-probe measurements. However, patient identification on the basis of Ga-HBED-CC-PSMA PET imaging as well as clinical parameters is crucial to obtain satisfactory results.

Contribution of SPECT/CT for sentinel node localization in patients with ipsilateral breast cancer relapse.

BACKGROUND: In recent years repeat sentinel node (SN) biopsy has been proven to be feasible in local breast cancer recurrence (LBCR). However, in these patients SNs outside the ipsilateral axilla are frequently observed. This study evaluates the contribution of SPECT/CT for SN localization and surgical adjustment in LBCR patients. METHODS: SN biopsy was performed in 122 LBCR patients (median age 60.5 years, range 24-87), enrolled from August 2006 to July 2015. Median disease-free time lapse was 109.5 months (range 9-365). Axillary lymph node dissection (ALND) had previously been performed in 55 patients, SN biopsy in 44, both techniques in 13 and fine-needle aspiration in 10. Primary breast cancer treatment included radiotherapy in 104 patients (85.3 %) and chemotherapy in 40 (32.8 %). Preoperative lymphatic mapping, using planar scintigraphy (PS) and SPECT/CT included report of SN location according to lymph node territory. In case of a territorial PS-SPECT/CT mismatch, surgery was adjusted according to SPECT/CT findings. RESULTS: SPECT/CT SN visualization rate was higher than PS (53.3 % vs. 43.4 %, p n.s.) with, in total, 19 additional SN (118 vs. 99, p n.s.). PS-SPECT/CT territory mismatch, found in 60 % (39/65) of patients with SN visualization, led to surgical adjustment in 21.3 % (26/122) of patients. The SN procedure was finally performed in 104 patients resulting in a 65.7 % surgical retrieval rate with a total of 132 removed SNs (1.86/patient). SN metastases were found in 17/71 patients (23.9 %), in 16 of them (94 %) in ipsilateral basins outside the axilla or in the contralateral axilla. CONCLUSION: Using SPECT/CT there is a trend to visualize more SNs in LBCR, providing at the same time important anatomical information to adjust intraoperative SN procedures. The addition of SPECT/CT to the standard imaging protocol may lead to better staging mainly in patients presenting drainage outside the ipsilateral axilla.

Value of 111 In-prostate-specific membrane antigen (PSMA)-radioguided surgery for salvage lymphadenectomy in recurrent prostate cancer: correlation with histopathology and clinical follow-up.

OBJECTIVES: To evaluate the use of 111 In-labelled prostate-specific membrane antigen (PSMA)-I&T-based radioguided surgery (111 In-PSMA-RGS) for salvage surgery in recurrent prostate cancer (PCa) using comparison of intra-operative gamma probe measurements with histopathological results of dissected specimens. In addition, to determine the success of 111 In-PSMA-RGS with regard to postoperative prostate-specific antigen (PSA) responses, PCa-specific treatment-free survival rates and postoperative complication rates. PATIENTS AND METHODS: A total of 31 consecutive patients with localized recurrent PCa undergoing salvage surgery with PSMA-targeted radioguided surgery using a 111 In-labelled PSMA ligand between April 2014 and July 2015 were retrospectively included in this study. The preoperative (interquartile range; range) median PSA level was 1.3 (0.57-2.53 ng/mL; 0.2-13.9 ng/mL). Results of ex vivo radioactivity rating (positive vs negative) of resected tissue specimens were compared with findings of postoperative histological analysis. Best PSA response without additional treatment was determined after 111 In-PSMA-RGS, and salvage-surgery-related postoperative complications and PCa-specific additional treatments were recorded. RESULTS: In 30/31 patients, 111 In-PSMA-RGS allowed intra-operative identification of metastatic lesions. In total, 145 surgical specimens were removed and 51 showed metastatic involvement at histological analysis. According to 111 In-PSMA-RGS ex vivo measurements, 48 specimens were correctly classified as metastatic and 87 as cancer-free, four were false-negative and six were false-positive compared with histological evaluation. Follow-up information was available for 30/31 patients. PSA declines of >50% and >90% were observed in 23/30 patients and in 16/30 patients, respectively. In 18/30 patients, a PSA decline to <0.2 ng/mL was observed. In 10/30 patients further PCa-specific treatment was given after a median (range) of 125 (48-454) days post-111 In-PSMA-RGS. The remaining 20 patients remained treatment-free at a median (range) follow-up of 337 (81-591) days. Of 30 patients, 10 presented with surgery-related complications (Clavien-Dindo grade 1, n = 6, Clavien-Dindo grade 3b, n = 4). CONCLUSION: 111 In-PSMA-RGS proved to be of high value for intra-operative detection of even small metastatic lesions in patients with PCa scheduled for salvage lymphadenectomy. It allows the exact localization and resection of metastatic tissue during 111 In-PSMA-RGS and is therefore anticipated to have a beneficial influence on further disease progression; however, identification of suitable patients on the basis of PSMA-positron-emission tomography imaging as well as clinical variables is essential for satisfactory results to be obtained.

PET-Probe: Evaluation of Technical Performance and Clinical Utility of a Handheld High-Energy Gamma Probe in Oncologic Surgery.

BACKGROUND: Positron emission tomography (PET) has become an invaluable part of patient evaluation in surgical oncology. PET is less than optimal for detecting lesions <1 cm, and the intraoperative localization of small PET-positive lesions can be challenging as a result of difficulties in surgical exposure. We undertook this investigation to assess the utility of a handheld high-energy gamma probe (PET-Probe) for intraoperative identification of 18F-deoxyglucose (FDG)-avid tumors. METHODS: Forty patients underwent a diagnostic whole-body FDG-PET scan for consideration for surgical exploration and resection. Before surgery, all patients received an intravenous injection of 7 to 10 mCi of FDG. At surgery, the PET-Probe was used to determine absolute counts per second at the known tumor site(s) demonstrated by whole-body PET and at adjacent normal tissue (at least 4 cm away from tumor-bearing sites). Tumor-to-background ratios were calculated. RESULTS: Thirty-two patients (80%) underwent PET-Probe-guided surgery with therapeutic intent in a recurrent or metastatic disease setting. Eight patients underwent surgery for diagnostic exploration. Anatomical locations of the PET-identified lesions were neck and supraclavicular (n = 8), axilla (n = 5), groin and deep iliac (n = 4), trunk and extremity soft tissue (n = 3), abdominal and retroperitoneal (n = 19), and lung (n = 2). PET-Probe detected all PET-positive lesions. The PET-Probe was instrumental in localization of lesions in 15 patients that were not immediately apparent by surgical exploration. CONCLUSIONS: The PET-Probe identified all lesions demonstrated by PET scanning and, in selected cases, was useful in localizing FDG-avid disease not seen with conventional PET scanning.

Radioguided localization of neuroblastomas in laparoscopic surgery using (123)I- radiolabeled metaiodobenzylguanidine.

Minimally invasive surgery has become widely recognized and is commonly used for the diagnosis and treatment of neuroblastoma. However, in post-chemotherapy status or during reoperations, it is occasionally difficult to precisely locate small neuroblastoma lesions, and this becomes prominent in endoscopic surgeries, in which tactile sense is essentially lost. Herein, we report our preliminary experience in two abdominal neuroblastoma cases undergoing laparoscopic tumor resection with aid of intraoperative (123)I- metaiodobenzylguanidine (MIBG) radioguidance using a specifically designed gamma-probe. The procedure enables easier localization of viable neuroblastoma tissue, provided that the tumor shows moderate to high MIBG uptake.

High-resolution, handheld camera use for occult breast lesion localization plus sentinel node biopsy (SNOLL): a single-institution experience with 186 patients.

BACKGROUND: Sentinel node and occult lesion localization (SNOLL) calls for a combination of two specific procedures: intraoperative detection of sentinel lymph node (SLN) via gamma probe and radioguided occult lesion localization (ROLL). This applies to nonpalpable invasive breast cancer or high-grade in situ carcinoma. As opposed to standard techniques, today's handheld gamma cameras enable intraoperative scintigraphic images. METHODS: A cohort (N = 186) of consecutive patients with breast cancer was subjected to radioguided conservative surgery (quadrantectomy and SLN biopsy), using a standard gamma probe and a high-resolution handheld camera. Intraoperative SLN frozen section was also performed. RESULTS: Neoplastic lesions were removed in 99.4% of all patients, and SLN biopsy was achieved in 99%. Of the 137 patients with invasive cancer, SLN metastasis was confirmed in 21. In 12% of patients, a second operation was required for close or tumor-positive surgical margins. DISCUSSION: This combination of procedures represents an improvement in the surgical management of occult breast carcinomas and is the method of choice for accurate tumor localization and SLN biopsy. Handheld cameras have the potential to become highly useful intraoperative aids.