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Purpose: To determine the lymphatic drainage pattern using SPECT/CT in clinically node-negative (cN0) patients with vulvar cancer, and to evaluate the possible implications for the extent of inguinal lymph node dissection. Methods: A total of 83 patients with vulvar cancer scheduled for sentinel node (SN) biopsy were injected peritumorally with radioactive nanocolloid particles followed by lymphoscintigraphy and SPECT/CT for anatomical localization. The SN and higher-echelon nodes on SPECT/CT were located in different zones in the groin and pelvic region. The groin was divided into five zones according to Daseler et al.: four zones obtained by drawing two perpendicular lines over the saphenofemoral junction and one zone directly overlying this junction. The nodes in the pelvic region were classified into three zones: external iliac/obturator, the common iliac and the paraaortic zones. Results: A total of 217 SNs and 202 higher-echelon nodes were localized on SPECT/CT. All SNs were located in the five zones according to Daseler et al.: 149 (69 %) in the medial superior region, 31 (14 %) in the medial inferior region, 22 (10 %) in the central region, 14 (6.5 %) in the lateral superior region and only 1 (0.5 %) in the lateral inferior region. The higher-echelon nodes were located both in the groin (15 %) and in the pelvic region (85 %). Conclusion: In patients with cN0 vulvar cancer, lymphatic drainage occurs predominantly to the medial regions of the groin. Drainage to the lateral inferior region of the groin is only incidental and in SN-positive patients this zone might be spared in subsequent extended lymph node dissection. This may lead to a decrease in the morbidity associated with this procedure. SPECT/CT is able to personalize lymphatic mapping, providing detailed information about the number and anatomical location of SNs for adequate surgical planning in the groin. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To define the correlation between the core biopsy location and the area with highest metabolic activity on 18F-FDG PET/CT in stage II–III breast cancer patients before neoadjuvant chemotherapy. Also, we would like to select a subgroup of patients in which PET/CT information may optimize tumor sampling. Methods: A PET/CT in prone position was acquired in 199 patients with 203 tumors. The distance and relative difference in standardized uptake value (SUV) between core biopsy localization (indicated by a marker) and area with highest degree of FDG uptake were evaluated. A distance ≥2cm and a relative difference in SUV ≥25% were considered clinically relevant and a combination of both was defined as non-correspondence. Non-correspondence for different tumor characteristics (TNM stage, lesion morphology on MRI and PET/CT, histology, subtype, grade, and Ki-67) was assessed. Results: Non-correspondence was found in 28 (14%) of 203 tumors. Non-correspondence was significantly associated with T-stage, lesion morphology on MRI and PET/CT, tumor diameter, and histologic type. It was more often seen in tumors with a higher T-stage (p =0.028), diffuse (non-mass) and multifocal tumors on MRI (p =0.001), diffuse and multifocal tumors on PET/CT (p <0.001), tumors >3cm (p <0.001), and lobular carcinomas (p <0.001). No association was found with other features. Conclusion: Non-correspondence between the core biopsy location and area with highest FDG uptake is regularly seen in stage II–III breast cancer patients. PET/CT information and possibly FDG-guided biopsies are most likely to improve pretreatment tumor sampling in tumors >3cm, lobular carcinomas, and diffuse and multifocal tumors. [Copyright &y& Elsevier]

Abstract: Annexin V imaging is suggested to provide a good indication of cancer treatment efficacy. To study the accuracy of 99mTc-AnxV imaging, we monitored chemo-sensitive and chemo-resistant tumors in a mouse breast cancer model after treatment with docetaxel. Sensitive tumors showed a slight peak in 99mTc-AnxV uptake one day post-treatment, while uptake in resistant tumors remained constant. In contrast to immunohistochemical analysis, 99mTc-AnxV imaging could not be used to predict tumor response, due to large variation between animals. [Copyright &y& Elsevier]

Background: The current expansion of image-guided surgery is closely related to the role played by radio-guided surgery in supporting the sentinel node (SN) procedure during more than three decades. The so-called triple approach (lymphoscintigraphy, gamma probe detection and blue dye) was not only essential in the seminal validation of the SN procedure but also a first collective learning effort based on skill transfer and outcome-related evaluation which laid the fundaments to delineate the field of intraoperative molecular imaging (IMI) based on a similar multimodality approach and multidisciplinary practice., Methods: These elements are also becoming valid in the current incorporation of SPECT/CT and PET/CT to existing and new protocols of IMI procedures and SN mapping concerning other clinical applications. On the other hand, there is a growing tendency to combine novel modern technologies in an allied role with gamma guidance in the operating room following the development of hybrid tracers and multimodal detection approaches. Against this background, learning initiatives are required for professionals working in this area., Results: This objective has led to a group of European practitioners with large experience in SN mapping and IMI applications to give shape to a programme made up out of specific learning modules aimed to be used as a conductive thread in peripherical or centralised training instances concerning the topic., Conclusion: The presented work, written as a tutorial review, is placed in an available prior-art context and is primarily aimed at medical and paramedical practitioners as well as at hardware and software developers., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of this review is to give an overview of the current status of molecular image-guided surgery in gynaecological malignancies, from both clinical and technological points of view., Methods: A narrative approach was taken to describe the relevant literature, focusing on clinical applications of molecular image-guided surgery in gynaecology, preoperative imaging as surgical roadmap, and intraoperative devices., Results: The most common clinical application in gynaecology is sentinel node biopsy (SNB). Other promising approaches are receptor-target modalities and occult lesion localisation. Preoperative SPECT/CT and PET/CT permit a roadmap for adequate surgical planning. Intraoperative detection modalities span from 1D probes to 2D portable cameras and 3D freehand imaging., Conclusion: After successful application of radio-guided SNB and SPECT, innovation is leaning towards hybrid modalities, such as hybrid tracer and fusion of imaging approaches including SPECT/CT and PET/CT. Robotic surgery, as well as augmented reality and virtual reality techniques, is leading to application of these innovative technologies to the clinical setting, guiding surgeons towards a precise, personalised, and minimally invasive approach., (© 2024. The Author(s).)

Since its origins, nuclear medicine has faced technological changes that led to modifying operating modes and adapting protocols. In the field of radioguided surgery, the incorporation of preoperative scintigraphic imaging and intraoperative detection with the gamma probe provided a definitive boost to sentinel lymph node biopsy to become a standard procedure for melanoma and breast cancer. The various technological innovations and consequent adaptation of protocols come together in the coexistence of the disruptive and the gradual. As obvious examples we have the introduction of SPECT/CT in the preoperative field and Drop-in probes in the intraoperative field. Other innovative aspects with possible application in radio-guided surgery are based on the application of artificial intelligence, navigation and telecare., (Copyright © 2023 Sociedad Española de Medicina Nuclear e Imagen Molecular. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: Although multiple radiopharmaceuticals are currently available for sentinel node (SN) biopsy, 99m Tc-tilmanocept is of particular interest due to its low molecular weight and specific binding capability for the mannose receptors of lymphatic reticuloendothelial cells. In the current systematic review and meta-analysis, we aimed to provide an update from a European expert panel on the performance of 99m Tc-tilmanocept for SN biopsy., Methods: A systematic literature search of the PubMed/Medline and Embase databases was performed to identify studies on the use of 99m Tc-tilmanocept for SN identification in oncological patients. The articles' methodological quality was assessed before inclusion. The pooled estimates of the pre-/intraoperative detection rates (DR; proportion of patients with ≥ 1 SN identified) and/or pN + sensitivity (SN + /pN + patients ratio), with 95% confidence intervals (CIs), were calculated for breast cancer, melanoma, and head and neck cancer., Results: Twenty-four articles were included in the systematic review, and twenty-one provided data for the meta-analysis. According to data availability, the 99m Tc-tilmanocept-estimated pooled preoperative and intraoperative DRs were 0.94 (95%CI, 0.88-1.01) and 0.99 (0.98-1.00) for breast cancer, 0.98 (0.96-0.99) and 1.00 (0.99-1.00) for melanoma, and 0.97 (0.93-1.02) and 0.99 (0.96-1.01) for head and neck carcinoma. Finally, the pooled sensitivity for nodal metastasis in melanoma was 0.97 (95% CI, 0.92-1.03)., Conclusion: 99m Tc-tilmanocept is a promising radiotracer for SN mapping in patients with breast cancer, melanoma, or head and neck cancer. We strongly believe that multicenter trials are still needed to assess if 99m Tc-tilmanocept is superior to other radiotracers used in clinical routine., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nuclear medicine has significantly contributed to precision surgery in breast cancer in the past decades. Radioguided surgery (RGS) has enabled sentinel node (SN) biopsy in assessing regional nodal involvement modifying the management of patients with early breast cancer. For the axilla the SN procedure has resulted in fewer complications and better quality of life when compared with axillary lymph node dissection. Originally, SN biopsy principally concerned cT 1-2 tumours without evidence of axillary lymph node metastases. However, in last years SN biopsy is also being offered to patients with large or multifocal tumours, ductal carcinoma in situ, ipsilateral breast cancer relapse, and to patients receiving neoadjuvant systemic treatment (NST) for breast sparing surgery. Parallel to this evolution various scientific associations are trying to homogenise issues such as radiotracer choice, breast injection site, preoperative imaging standardisation and SN biopsy timing in relation to NST as well as management of non-axillary SN metastasis (e.g. internal mammary chain). Additionally, RGS is currently used to accomplish primary breast tumour excision either by intralesional radiocolloid injection or by radioactive iodine seed implantation which is also employed to target metastatic axillary lymph nodes. This latter procedure contributes to manage the node-positive axilla in combination with 18 F-FDG PET/CT in an effort to tailor systemic and loco regional treatment., (Copyright © 2023 Sociedad Española de Medicina Nuclear e Imagen Molecular. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: Improvements in molecular breast imaging (MBI) have increased the use of MBI as adjunct diagnostic modality and alternative to MRI. We aimed to assess the value of MBI in patients with equivocal breast lesions on conventional imaging, especially in terms of its ability to rule out malignancy., Methods: We selected patients who underwent MBI in addition to conventional diagnostics due to equivocal breast lesions between 2012 and 2015. All patients underwent digital mammography, target ultrasound and MBI. MBI was performed using a single-head Dilon 6800 gamma camera after administration of 600 MBq 99m Tc-sestamibi. Imaging was reported according to BI-RADS classification and compared with pathology or follow-up of ≥6 months., Results: Of 226 women included, pathology was obtained in 106 (47%) and (pre)malignant lesions were found in 25 (11%). Median follow-up was 5.4 years (IQR 3.9-7.1). Sensitivity was higher for MBI compared to conventional diagnostics (84% vs. 32%; P  = 0.002), identifying malignancy in 21 and 6 patients, respectively, but specificity did not differ (86% vs. 81%; P  = 0.161). Positive and negative predictive value were 43% and 98% for MBI and 17% and 91% for conventional diagnostics. MBI was discordant with conventional diagnostics in 68 (30%) patients and correctly changed diagnosis in 46 (20%) patients, identifying 15 malignant lesions. In subgroups with nipple discharge ( N  = 42) and BI-RADS 3 lesions ( N  = 113) MBI detected 7 of 8 occult malignancies., Conclusion: MBI correctly adjusted treatment in 20% of patients with diagnostic concerns after conventional work-up, and could rule out malignancy with a high negative predictive value of 98%., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Breast cancer is the most frequent cancer diagnosed in women worldwide. Accurate lymph node staging is essential for both prognosis (of early-stage disease) and treatment (for regional control of disease) in patients with breast cancer. The sentinel lymph nodes are the regional nodes that directly drain lymph from the primary tumor. No imaging modality is accurate enough to detect lymph node metastases when a primary breast cancer is at an early stage (I or II), but sentinel lymph node biopsy is a highly reliable method for screening axillary nodes and for identifying metastatic (including micro-metastatic) disease in regional lymph nodes. Despite the widespread use of sentinel lymph node biopsy for early-stage breast cancer, relevant variations have been described regarding practical aspects of the procedure, and some variability has initially been reported regarding the rates of intraoperative sentinel lymph node identification and of false-negative findings, most likely because of differences in the size of the populations being investigated and in lymphatic mapping techniques. Nevertheless, using adequate learning curves and once a multidisciplinary team is experienced with the procedure, improved levels of accuracy are achieved., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: In muscle-invasive bladder cancer (MIBC), lymph node invasion has proven to be an independent predictor of disease recurrence and cancer-specific survival. We evaluated the feasibility of targeting the sentinel node (SN) for biopsy in MIBC patients using the hybrid tracer indocyanine green (ICG)- 99m Tc-nanocolloid for simultaneous radioguidance and fluorescence guidance., Methods: Twenty histologically confirmed cN0M0 MIBC patients (mean age, 63.3 years; range, 30-82 years), scheduled for radical cystectomy with SN biopsy and extended pelvic lymph node dissection (ePLND), were prospectively included. Twelve patients were operated on following neoadjuvant chemotherapy. The patients received lymphoscintigraphy as well as SPECT/CT after 4 transurethral injections of ICG- 99m Tc-nanocolloid (mean, 208 MBq; range, 172-229 MBq) around the tumor/scar in the detrusor muscle of the bladder on the day before radical cystectomy. Sentinel node resection was performed under radioguidance and fluorescence guidance., Results: Nineteen patients could be analyzed. On preoperative imaging, SNs could be identified in 10 patients (53%; mean, 1.6 SN/patient), which revealed drainage pathways outside the ePLND in 20% of the patients. Interesting to note is that 2 patients (10%) with preoperative nonvisualization displayed fluorescent and radioactive SNs during surgery. Location of the primary tumor near the left lateral side of the bladder seemed to be a factor for nonvisualization. Nodal harvesting with ePLND varied among patients (mean, 23.3). Histopathology confirmed tumor-positive nodes in 4 (21%) of all patients. In the 2 patients where an SN could be identified, the ePLND specimens were tumor-negative. All patients with tumor-positive nodes had advanced disease (stage III)., Conclusion: Sentinel node biopsy in bladder cancer using the hybrid tracer ICG- 99m Tc-nanocolloid is feasible, and preoperative imaging is predictive for the ability to perform SN biopsy in 83% of the patients who displayed an SN. In patients with a successful preoperative SN mapping using lymphoscintigraphy and SPECT/CT, the intraoperative SN guidance and detection were effective, even outside the ePLND area. As such, this study underscores the critical role that preoperative imaging plays in challenging image-guided surgery applications., Competing Interests: Conflicts of interest and sources of funding: This work was partially supported by an NWO-STW-VIDI grant (grant STW BGT11272). There are no potential conflicts of interest or payments received from a third party., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Recent technical advances and implementation of novel radiotracers have further increased the potential of radioguided surgery for a broad variety of malignancies. Indeed, the possibilities for future applications of novel radiotracers in diverse oncological strategies has become more promising than ever. This literature review aims to provide a contemporary update on a selected group of radiotracers and evaluates the usability of radioguided surgery and sentinel node procedures, focusing on most promising advances. For example, the impact of targeted radiotracers on prostate specific membrane antigen (PSMA), CD206 receptor-targeted agents ( 99m Tc-tilmanocept), and hybrid tracers adding fluorescence to radioguidance (ICG- 99m Tc-nanocolloid) as well as targeting hypoxia-induced carbonic anhydrase IX (CAIX) will be covered. Furthermore, future outlooks on the implementation of gold nanoparticles (AuNP's), but also technical advances in improved radiotracer detection by hybrid gamma devices will be discussed.

We review recent technological advances and new clinical indications for sentinel node (SN) and radioguided surgery in order to delineate future tendencies of interventional nuclear medicine in this field. A literature research was performed in PubMed to select relevant articles to be used as key references for analysis of the current approaches and tendencies in SN and radioguided surgery, as well as the evolving contribution of nuclear medicine intervention techniques to the various clinical applications. For classic indications such as melanoma and breast cancer, the incorporation of the SN approach based on the combined use of existing and new preoperative and intraoperative technologies in high-risk patient categories is becoming an emerging area of clinical indication. For SN biopsy staging in other malignancies with more complex lymphatic drainage, the incorporation of sophisticated tools is most helpful. The consecutive use of PET/CT and the SN procedure is increasing as a potential combined approach for the management of specific areas such as the axilla and the pelvis in patients at high risk of regional dissemination. Also, for the management of locoregional metastasis and oligometastatic disease, interventional nuclear medicine techniques are becoming valuable alternatives. The extended experience with SN biopsy is leading to technological advances facilitating the incorporation of this procedure to stage other malignancies with complex lymphatic drainage. New nuclear medicine-based approaches, incorporating SPECT/CT and PET/CT to guide resection of SNs and occult metastases, have recently been gaining ground.

Objective: The hybrid tracer indocyanine green (ICG)-Tc-nanocolloid has been introduced for sentinel node imaging. However, until now, a comparison of this tracer with other radiocolloids with a larger particle size has not been effectuated. Based on a head-to-head evaluation in patients with melanoma, we have compared ICG-Tc-nanocolloid (particle size 5-80 nm) with Tc-Senti-Scint (particle size 100-600 nm) to establish differences in drainage pattern and sentinel node localization using lymphoscintigraphy and single-photon emission computed tomography combined with computer tomography (SPECT-CT) in melanoma patients scheduled for sentinel node biopsy., Methods: Twenty-five patients (mean age: 56.9 years, range: 25-79 years) with a melanoma scheduled for SLN biopsy prior to (re)excision of the primary lesion (scar) were prospectively included following a two-day procedure. The first day, after Tc-Senti-Scint injection in four intradermal depots around the primary lesion or scar, early/delayed lymphoscintigraphy and SPECT-CT images were acquired. The injection sites were marked. The second day, after assessing lymph node radioactivity using planar scintigraphy, ICG-Tc-nanocolloid was injected at the previously marked skin points and imaging was performed. The paired planar and SPECT-CT images of both tracers were evaluated with respect to drainage patterns, SLN visualization and non-SLN appearing., Results: Twenty-four out of 25 patients were evaluable. SLN visualization on a patient basis was 100% for ICG-Tc-nanocolloid and 96% for Tc-Senti-Scint, whereas uptake in non-SLNs was found in, respectively, 71% (17/24) and 61% (14/23). Concordance in drainage to 45 lymph node basins was 91%. Discordant drainage was found for two melanomas in the head-and-neck and one in the clavicular area. Unique lymph node basins were seen in 44/45 (98%) for ICG-Tc-nanocolloid and 42/45 (93%) for Tc-Senti-Scint. Concerning identified SLNs, the number was similar for both tracers (n = 58); however, more non-SLNs (65 vs 50) were visualized with ICG-Tc-nanocolloid than with Tc-Senti-Scint., Conclusion: A slightly higher SLN visualization accompanied by a tendency to depict more non-SLNs was found for ICG-Tc-nanocolloid. Excepting the head and neck area, an overall high concordance in drainage was found for both radiotracers. With an additional value for the hybrid tracer due to the combination of preoperative imaging and the additional visual signal in the operation room, added by the fluorescent component of the hybrid tracer, there was a preference for ICG-Tc-nanocolloid.

For radical resection of squamous cell carcinoma of the oral cavity, a tumor-free margin of at least 5 mm is required. Unfortunately, establishing in-depth margins is a surgical conundrum. Knowing that the hybrid sentinel node (SN) tracer indocyanine green (ICG)- 99m Tc-nanocolloid generates temporary tattoolike markings at the site of administration, we studied the ability to apply this tracer for tumor margin demarcation combined with SN biopsy. Methods: Nineteen patients with clinical T1-T2 oral tongue tumors received the traditional superficial 3 or 4 deposits of ICG- 99m Tc-nanocolloid (0.1 mL each), and in 12 patients additional deposits were placed deeply using ultrasound guidance (total of 6; 0.07 mL each). SN mapping was performed using lymphoscintigraphy and SPECT/CT. Before and directly after tumor excision, fluorescence imaging was performed to monitor the tracer deposits in the patient (fluorescent deposits were not used to guide the surgical excision). At pathologic examination, primary tumor samples were studied in detail. Results: The number of tracer depositions did not induce a significant difference in the number of SNs visualized ( P = 0.836). Reproducible and deep tracer deposition proved to be challenging. The fluorescent nature of ICG- 99m Tc-nanocolloid supported in vivo and ex vivo identification of the tracer deposits surrounding the tumor. Pathologic examination indicated that in 66.7% (8/12), all fluorescence was observed within the resection margins. Conclusion: This study indicates that tumor margin demarcation combined with SN identification has potential but that some practical challenges need to be overcome if this technique is to mature as a surgical guidance concept. Future studies need to define whether the technology can improve the radical nature of the resections., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

This study investigates whether radiomic features derived from preoperative positron emission tomography (PET) images could predict both tumor biology and prognosis in women with invasive squamous cell carcinoma of the vulva. Methods: Patients were retrospectively included when they had a unifocal primary cancer of ≥ 2.6 cm in diameter, had received a preoperative 18 F-fluorodeoxyglucose ( 18 F-FDG) PET/computed tomography (CT) scan followed by surgery and had at least six months of follow-up data. 18 F-FDG-PET images were analyzed by semi-automatically drawing on the primary tumor in each PET image, followed by the extraction of 83 radiomic features. Unique radiomic features were identified by principal component analysis (PCA), after which they were compared with histopathology using non-pairwise group comparison and linear regression. Univariate and multivariate Cox regression analyses were used to correlate the identified features with progression-free survival (PFS) and overall survival (OS). Survival curves were estimated using the Kaplan-Meier method. Results: Forty women were included. PCA revealed four unique radiomic features, which were not associated with histopathologic characteristics such as grading, depth of invasion, lymph-vascular space invasion and metastatic lymph nodes. No statistically significant correlation was found between the identified features and PFS. However, Moran's I, a feature that identifies global spatial autocorrelation, was correlated with OS ( P = 0.03). Multivariate Cox regression analysis showed that extracapsular invasion of the metastatic lymph nodes and Moran's I were independent prognostic factors for PFS and OS. Conclusion: Our data show that PCA is usable to identify specific radiomic features. Although the identified features did not correlate strongly with tumor biology, Moran's I was found to predict patient prognosis. Larger studies are required to establish the clinical relevance of the observed findings., (Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Purpose: Lymphatic drainage from renal tumors is unpredictable. In vivo drainage studies of primary lymphatic landing sites may reveal the variability and dynamics of lymphatic connections. The purpose of this study was to investigate the lymphatic drainage pattern of renal tumors in vivo with single photon emission/computerized tomography after intratumor radiotracer injection., Materials and Methods: We performed a phase II, prospective, single arm study to investigate the distribution of sentinel nodes from renal tumors on single photon emission/computerized tomography. Patients with cT1-3 (less than 10 cm) cN0M0 renal tumors of any subtype were enrolled in analysis. After intratumor ultrasound guided injection of 0.4 ml 99m Tc-nanocolloid we performed preoperative imaging of sentinel nodes with lymphoscintigraphy and single photon emission/computerized tomography. Sentinel and locoregional nonsentinel nodes were resected with a γ probe combined with a mobile γ camera. The primary study end point was the location of sentinel nodes outside the locoregional retroperitoneal templates on single photon emission/computerized tomography. Using a Simon minimax 2-stage design to detect a 25% extralocoregional retroperitoneal template location of sentinel nodes on imaging at α = 0.05 and 80% power at least 40 patients with sentinel node imaging on single photon emission/computerized tomography were needed., Results: Of the 68 patients 40 underwent preoperative single photon emission/computerized tomography of sentinel nodes and were included in primary end point analysis. Lymphatic drainage outside the locoregional retroperitoneal templates was observed in 14 patients (35%). Eight patients (20%) had supradiaphragmatic sentinel nodes., Conclusions: Sentinel nodes from renal tumors were mainly located in the respective locoregional retroperitoneal templates. Simultaneous sentinel nodes were located outside the suggested lymph node dissection templates, including supradiaphragmatic sentinel nodes in more than a third of the patients., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Interest in technetium-99m ( 99m Tc)-sestamibi imaging for neoadjuvant chemotherapy (NAC) response monitoring in locally advanced breast cancer (LABC) is increasing but remains matter of discussion. The present study conducted a meta-analysis of the diagnostic performance of 99m Tc-sestamibi to predict pathologic nonresponse to NAC for primary LABC., Materials and Methods: A systematic data search was performed. Studies with a minimum of 10 LABC patients that had evaluated 99m Tc-sestamibi imaging for NAC nonresponse using conventional planar scintimammography, breast-specific γ-imaging, and/or single photon emission computed tomography/computed tomography (SPECT/CT) were included. The histopathologic findings were the reference standard. The meta-analysis was performed using a mixed logistic regression model., Results: The search revealed 14 eligible studies with 529 patients. Of the 14 studies, 11 had evaluated scintimammography and 3 breast-specific γ-imaging. No studies examining SPECT or SPECT/CT were found. The overall estimated pooled sensitivity, specificity, and positive and negative likelihood ratios of 99m Tc-sestamibi imaging to predict nonresponsiveness to NAC were 70.3% (95% confidence interval [CI], 56.5%-81.3%%), 90.1% (95% CI, 77.5%-96.0%), 7.13 (95% CI, 3.08-16.53), and 0.33 (95% CI, 0.22-0.49), respectively. Only 3 studies (107 patients) evaluated 99m Tc-sestamibi imaging during NAC, reported an estimated pooled sensitivity of 87% (95% CI, 72%-100%) and specificity of 93% (95% CI, 85%-100%)., Conclusion: Only planar 99m Tc-sestamibi imaging has been investigated for NAC nonresponse in LABC but showed low sensitivity to predict pathologic nonresponse. However, most studies focused on the prediction of pathologic complete response after NAC. Although experience is limited, 99m Tc-sestamibi uptake during NAC seems highly sensitivity for the prediction of nonresponsiveness. Features such as SPECT/CT imaging, standardized quantification, relation to tumor subtypes, and proper timing have been insufficiently evaluated and require further investigation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This study aimed to assess the value of dual-timepoint 18 F-FDG PET/CT in the prediction of lymph node (LN) status in patients with invasive vulvar cancer (VC) scheduled for inguinofemoral LN dissection. Methods: From April 2013 to July 2015, all consecutive patients with VC scheduled for inguinofemoral LN dissection were prospectively enrolled. All patients underwent a preoperative whole-body 18 F-FDG PET/CT scan at 1 h (standard examination) and an additional scan from T11 to the groins at 3 h (delayed examination) after 18 F-FDG injection. On both scans, each groin was visually scored 0 or 1 concerning 18 F-FDG LN uptake relative to background. Semiquantitative analysis included SUV max and the corresponding retention index of SUV max , measured on both scans. The optimal cutoff value of these parameters was defined using a receiver-operating-characteristic analysis. Histopathology was the standard of reference. Results: Thirty-three patients were included, with a total of 57 groins dissected and histologically evaluated. At histopathology, 21 of 57 (37%) groins contained metastatic LNs. Concerning visual score, sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were 95.2%, 75%, 96.4%, 69%, and 82.5% on standard scanning and 95.2%, 77.8%, 96.6%, 71.4%, and 84.2% on delayed scanning, respectively. At receiver-operating-characteristic analysis, sensitivity and specificity were 95.2% and 77.8% on standard and delayed 18 F-FDG PET/CT for an SUV max cutoff of greater than 1.32 and 1.88, respectively, and 95.2% and 80% for a retention index of SUV max cutoff of greater than 0. Conclusion: Standard 18 F-FDG PET/CT is an effective preoperative imaging method for the prediction of LN status in VC, allowing the prediction of pathologically negative groins and thus the selection of patients suitable for minimally invasive surgery. Delayed 18 F-FDG PET/CT did not improve the specificity and the positive predictive value in our series. Larger studies are needed for a further validation., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: 18 F-FDG PET/CT can monitor metabolic activity in early breast cancer during neoadjuvant systemic therapy (NST), but it is unknown if the metabolic breast and axillary response differ. We evaluated the correlation between metabolic breast and axillary response at various time points during NST. Furthermore, we analysed if the combined metabolic response improves pathologic complete response (pCR) prediction compared to using the metabolic breast response alone., Methods: 18 F-FDG PET/CT was performed at baseline (PET1), 2-3 weeks (PET2), and 6-8 weeks (PET3) of NST in patients with triple-negative (TN) and HER2-positive node-positive breast cancer. SUVmax and ∆SUVmax were determined separately for breast and axilla. Spearman's correlation coefficients (r) between both localisations were calculated. The accuracy of pCR total (ypT0/is,ypN0) prediction using the metabolic response in breast, axilla or both was examined using logistic regression analysis., Results: Hundred-five patients were included: 45 TN and 60 HER2-positive tumours. The metabolic response in breast and axilla correlated moderately in TN tumours (r = 0.57) using ∆SUVmax between PET1-PET3 and poorly in HER2-positive tumours (r = 0.49) using SUVmax at PET2. In TN tumours, metabolic breast response predicted pCR well without improvement after adding axillary response (c-index 0.82 versus 0.85, p = 0.63). In HER2-positive tumours, metabolic breast response predicted pCR poorly with improvement after adding axillary response (c-index 0.64 versus 0.72, p = 0.06)., Conclusions: 18 F-FDG PET/CT response during NST differs between breast and axilla. In TN tumours, pCR total prediction can be made independent of metabolic axillary response. In HER2-positive tumours, axillary response may improve pCR total prediction. These findings may help guide PET/CT-response-based changes during NST., Trial Registration: NTR NTR1797 . Registered 29 May 2009, retrospectively registered.

Introduction: In this study we evaluated the value of pre-operative glucose corrected maximum standard uptake value (GC-SUVmax) as prognostic factor in patients with early stage non-small cell lung cancer (NSCLC) after complete surgical resection., Methods: This study was designed as a retrospectively evaluated single center study with prospective data registry. Inclusion criteria were: histologically proven stage I NSCLC, 18F-FDG-PET/CT scan prior to surgery, complete resection (R0) and follow up in our outpatient department. Exclusion criteria were: history of malignancy other than NSCLC, diabetes and (neo) adjuvant therapy. Follow up period was 5 years., Results: Between 2006 and 2008 a total of 33 patients (16 males, 17 females) met the inclusion criteria. SUVmax and GC-SUVmax were strongly correlated (Spearman's ρ = 0.97). Five-year overall survival (OS) rate was 70 % (95 % CI = 56-87 %). Patients who died within 5 years of follow up had significantly higher pre-operative GC-SUVmax (median = 10.6, IQR = 8.3-14.4) than patients who were alive at 5-year follow up (median = 6.4, IQR = 3.0-9.8), p = 0.04. SUVmax showed similar differences: 10.4 (8-12.9) vs. 6.6 (3.0-8.8), p = 0.047. The area under the receiver-operating characteristic (ROC) curve at 5 years was 0.70 (95 % CI = 0.50-0.90) for GC-SUVmax and 0.71 (95 % CI = 0.51-0.91) for SUVmax (p = 0.75)., Conclusion: Pre-operative FDG tumor uptake in patients with NSCLC is predictive for survival after complete surgical resection. GC-SUVmax, as an additional value to SUVmax, may better approach competitive inhibition of FDG and glucose in tumors, however, in this study this potential advantage, if any, was very small.

Objective: The purposes of this study were to evaluate the performance of a mammography with molecular imaging PET (MAMMI-PET) system for breast imaging in the hanging-breast position for the visualization of primary breast cancer lesions and to compare this method with whole-body PET/CT., Subjects and Methods: Between March 2011 and March 2014, a prospective evaluation included women with one or more histologically confirmed primary breast cancer lesions (index lesions). After injection of 180-240 MBq of (18)F-FDG, whole-body PET/CT and MAMMI-PET acquisitions were performed, index lesions were scored 0, 1, or 2 for FDG uptake relative to background. Detection and FDG uptake were compared by breast length, maximal tumor diameter, affected breast quadrants, tumor grade, and histologic and immunologic sub-types. Finally, the two PET modalities were compared for detection of index lesions., Results: For 234 index lesions (diameter, 5-170 mm), the overall sensitivity was 88.9% for MAMMI-PET and 91% for PET/CT (p = 0.61). Twenty-three (9.8%) index lesions located too close to the pectoral muscle were missed with MAMMI-PET, and 20 index lesions were missed with PET/CT. Lesion visibility on MAMMI-PET images was influenced by tumor grade (p = 0.034) but not by cancer subtype (p = 0.65)., Conclusion: Although in an overall evaluation MAMMI-PET was not superior to PET/CT, MAMMI-PET does have higher sensitivity for primary breast cancer lesions within the scanning range of the device. Optimization of the positioning device may increase visualization of the most dorsal lesions.

Purpose: Freehand single-photon emission computed tomography (SPECT) (fh-SPECT) for optical tracked 3-dimensional radioactivity mapping raises popularity for sentinel node biopsy and other radio-guided procedures. However, the device seems to be complex, requiring both training and a standardized scan protocol. Therefore, the aim of this study was to compare handling reproducibility between novice and expert users; subsequently, using additional scans, we evaluated a standardized scan protocol to be tested in novice users after receiving training., Materials and Methods: Three groups (untrained novices, experts, and trained novices), each one composed of 5 fh-SPECT users, were given the same short introduction and the assignment to perform 3 fh-SPECT scans with the same time per scan. For the scans, a reproducible phantom with an iodine-125 point source was used. Furthermore, we performed probe-trajectory evaluation including pattern, speed, and length of scans based on recorded videos and digital target tracking., Results: The training period encompasses 30 minutes per novice user. The mean error in 3 directions based on 45 measurements was 7.4 mm for untrained novices and 3.2 mm for expert users. The trained novice group had a mean error of 2.9 mm (a significant 61% reduction), comparable to the expert group. The reproducibility values, expressed in SD, were 4.1 mm for the untrained novice group, 1.3 mm for the expert group, and 1.1 mm for the trained novices (73% improvement). The standardized scan protocol was demonstrated by means of trajectory evaluation, a scan path better systematized., Conclusion: Scanning with fh-SPECT for radio-guided surgery requires a specific training period to increase handling and reproducibility of 3-dimensional imaging, and to enhance its accuracy in the operating room.

Purpose To evaluate the hybrid approach in a large population of patients with melanoma in the head and neck, on the trunk, or on an extremity who were scheduled for sentinel node (SN) biopsy. Materials and Methods This prospective study was approved by the institutional review board. Between March 2010 and March 2013, 104 patients with a melanoma, including 48 women (average age, 54.3 years; range, 18.5-87.4 years) and 56 men (average age, 55.2 years; range, 22.4-77.4 years) (P = .76) were enrolled after obtaining written informed consent. Following intradermal hybrid tracer administration, lymphoscintigraphy and single photon emission computed tomography/computed tomography were performed. Blue dye was intradermally injected prior to the start of the surgical operation (excluding patients with a facial melanoma). Intraoperatively, SNs were initially pursued by using gamma tracing followed by fluorescence imaging (FI) and, when applicable, blue-dye detection. A portable gamma camera was used to confirm SN removal. Collected data included number and location of the preoperatively and intraoperatively identified SNs and the intraoperative number of SNs that were radioactive, fluorescent, and blue. A two-sample test for equality of proportions was performed to evaluate differences in intraoperative SN visualization through FI and blue-dye detection. Results Preoperative imaging revealed 2.4 SNs (range, 1-6) per patient. Intraoperatively, 93.8% (286 of 305) of the SNs were radioactive, 96.7% (295 of 305) of the SNs were fluorescent, while only 61.7% (116 of 188) of the SNs stained blue (P < .0001). FI was of value for identification of near-injection-site SNs (two patients), SNs located in complex anatomic areas (head and neck [28 patients]), and SNs that failed to accumulate blue dye (19 patients). Conclusion The hybrid tracer enables both preoperative SN mapping and intraoperative SN identification in melanoma patients. In the setup of this study, optical identification of the SNs through the fluorescent signature of the hybrid tracer was superior compared with blue dye-based SN visualization.

Wire-guided localization is the most commonly used technique for intraoperative localization of non-palpable breast cancer. Radioactive seed localization (RSL) is becoming more popular and seems to be a reliable alternative for intraoperative lesion localization. The purpose of the present meta-analysis was to evaluate the use of RSL. Primary study outcomes were irradicality and re-excision rates. In total 3168 patients were included. The clinical adaptation shows growing confidence in RSL and further growth is expected., (© 2014 Wiley Periodicals, Inc.)

Background: The hybrid tracer was introduced to complement intraoperative radiotracing towards the sentinel nodes (SNs) with fluorescence guidance., Objective: Improve in vivo fluorescence-based SN identification for prostate cancer by optimising hybrid tracer preparation, injection technique, and fluorescence imaging hardware., Design, Setting, and Participants: Forty patients with a Briganti nomogram-based risk >10% of lymph node (LN) metastases were included. After intraprostatic tracer injection, SN mapping was performed (lymphoscintigraphy and single-photon emission computed tomography with computed tomography (SPECT-CT)). In groups 1 and 2, SNs were pursued intraoperatively using a laparoscopic gamma probe followed by fluorescence imaging (FI). In group 3, SNs were initially located via FI. Compared with group 1, in groups 2 and 3, a new tracer formulation was introduced that had a reduced total injected volume (2.0 ml vs. 3.2 ml) but increased particle concentration. For groups 1 and 2, the Tricam SLII with D-Light C laparoscopic FI (LFI) system was used. In group 3, the LFI system was upgraded to an Image 1 HUB HD with D-Light P system., Intervention: Hybrid tracer-based SN biopsy, extended pelvic lymph node dissection, and robot-assisted radical prostatectomy., Outcome Measurements and Statistical Analysis: Number and location of the preoperatively identified SNs, in vivo fluorescence-based SN identification rate, tumour status of SNs and LNs, postoperative complications, and biochemical recurrence (BCR)., Results and Limitations: Mean fluorescence-based SN identification improved from 63.7% (group 1) to 85.2% and 93.5% for groups 2 and 3, respectively (p=0.012). No differences in postoperative complications were found. BCR occurred in three pN0 patients., Conclusions: Stepwise optimisation of the hybrid tracer formulation and the LFI system led to a significant improvement in fluorescence-assisted SN identification. Preoperative SPECT-CT remained essential for guiding intraoperative SN localisation., Patient Summary: Intraoperative fluorescence-based SN visualisation can be improved by enhancing the hybrid tracer formulation and laparoscopic fluorescence imaging system., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: We explored the clinical feasibility and accuracy of intraoperative navigation based on preoperatively acquired 3-dimensional functional imaging data., Materials and Methods: Ten patients with penile carcinoma scheduled for sentinel node biopsy were prospectively included in study. After tracer injection preoperative single photon emission computerized tomography/computerized tomography was performed with a reference target fixed on the patient. Repositioning a sterile reference target shortly before surgery allowed 3-dimensional single photon emission computerized tomography/computerized tomography mixed reality based navigation of the γ probe (also containing a reference target) to the sentinel node. The accuracy of the declipse®SPECT navigation approach was determined in relation to the incision site indicated by the conventional γ probe in the coronal plane and the depth estimation measured on axial computerized tomography slices in the sagittal/axial plane., Results: The 3-dimensional mixed reality approach enabled γ probe navigation toward the sentinel node in all 10 patients. The average ± SD navigation error in the coronal and saggital/axial planes was 5.0 ± 3.9 and 5.3 ± 3.9 mm, respectively., Conclusions: To our knowledge this is the first study demonstrating the feasibility of intraoperative navigation based on preoperatively acquired 3-dimensional single photon emission computerized tomography/computerized tomography images. Although confirmation of successful target localization (eg using γ tracing or fluorescence imaging) remains indispensable, this opens the way to translate 3-dimensional functional imaging data to the operating room., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To prospectively evaluate diagnostic computed tomography (CT) and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for identification of histopathologic response to neoadjuvant erlotinib, an epidermal growth factor receptor-tyrosine kinase inhibitor in patients with resectable non-small cell lung cancer (NSCLC)., Methods: This study was designed as an open-label phase 2 trial, performed in four hospitals in the Netherlands. Patients received preoperative erlotinib 150 mg once daily for 3 weeks. CT and FDG-PET/CT were performed at baseline and after 3 weeks of treatment. CT was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. FDG-PET/CT, tumor FDG uptake, and changes were measured by standardized uptake values (SUV). Radiologic and metabolic responses were compared to the histopathological response., Results: Sixty patients were enrolled onto this study. In 53 patients (22 men, 31 women), the combination of CT, FDG-PET/CT, and histopathological evaluation was available for analysis. Three patients (6 %) had radiologic response. According to European Organisation for Research and Treatment of Cancer (EORTC) criteria, 15 patients (28 %) showed metabolic response. In 11 patients, histopathologic response (≥50 % necrosis) was seen. In predicting histopathologic response, relative FDG change in SUVmax showed more SUVmax decrease in the histopathologic response group (-32 %) versus the group with no pathologic response (-4 %) (p = 0.0132). Relative change in tumor size on diagnostic CT was similar in these groups with means close to 0., Conclusions: FDG-PET/CT has an advantage over CT as a predictive tool to identify histopathologic response after 3 weeks of EGFR-TKI treatment in NSCLC patients.

Purpose: Radioactive seed localization (RSL) uses an iodine-125 ((125)I) seed as a marker for tumour location. The (125)I seed is implanted into the tumour and enables intraoperative localization with a conventional gamma probe. However, specimen margins in relation to the (125)I seed are estimated on the basis of gamma-probe readings only. A novel device, freehand SPECT, is capable of measuring the distance from the resection plane to the (125)I seed. The aim of this feasibility study was to establish the accuracy of this device in predicting resection margins in ex-vivo tumour specimens excised with RSL guidance., Patients and Methods: In this feasibility study 10 patients with nonpalpable breast cancer scheduled for wide local excision with RSL were included. After surgery, the specimens containing the breast tumour and the (125)I seed were scanned using freehand SPECT. Measurements from five directions were taken and compared with distances measured by means of an ex-vivo computed tomographic (CT) scan and related to the pathology report., Results: The difference between freehand SPECT and CT measurements was 2.9±2.7 mm (mean±SD). One patient had a positive margin based on freehand SPECT. This specimen contained a focal irradical resection ventral of the tumour based on the pathology report. The smallest distance to the (125)I seed was 4 mm for the freehand SPECT and 5 mm for the CT scan., Conclusion: Accurate ex-vivo measurements of the tumour resection margins using (125)I seeds and freehand SPECT are feasible in patients undergoing breast-conserving surgery. Incorporation of the freehand-SPECT device in RSL protocols may enable a real-time estimation of resection margins, which may be useful for surgeons to adjust resection planes.

Supported by a large body of published work, the contribution of nuclear medicine technologies to the assessment of melanoma has been increasing in recent years. Lymphoscintigraphy-assisted sentinel lymph node biopsy and PET are in continuous evolution with the aid of technological imaging advances, making it possible to fuse functional and anatomic images (e.g., with SPECT/CT, PET/CT and 3D rendering systems). The development of hybrid fluorescent-radioactive tracers that enable high-quality preoperative lymphoscintigraphy and SPECT/CT, and the optimization of modern intraoperative portable imaging technologies, such as free-hand SPECT and portable γ-cameras, are important innovations that have improved sentinel lymph node identification in complex anatomical areas, such as the pelvis and head and neck. Concurrently, 18 F-fluorodeoxyglucose-PET has proved its usefulness in the clinical staging and treatment decision-making process, and there is also emerging evidence regarding its utility in the evaluation of therapeutic response. The potential uses of other novel PET radiotracers could open up a new field of use for this technique. In this article, we review the current and future role of nuclear medicine in the management of melanoma., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Purpose: To explore the potential complementary value of PET/CT and dynamic contrast-enhanced MRI in predicting pathological response to neoadjuvant chemotherapy (NAC) of breast cancer and the dependency on breast cancer subtype., Methods: We performed (18)F-FDG PET/CT and MRI examinations before and during NAC. The imaging features evaluated on both examinations included baseline and changes in (18)F-FDG maximum standardized uptake value (SUVmax) on PET/CT, and tumour morphology and contrast uptake kinetics on MRI. The outcome measure was a (near) pathological complete response ((near-)pCR) after surgery. Receiver operating characteristic curves with area under the curve (AUC) were used to evaluate the relationships between patient, tumour and imaging characteristics and tumour responses., Results: Of 93 patients, 43 achieved a (near-)pCR. The responses varied among the different breast cancer subtypes. On univariate analysis the following variables were significantly associated with (near-)pCR: age (p = 0.033), breast cancer subtype (p < 0.001), relative change in SUVmax on PET/CT (p < 0.001) and relative change in largest tumour diameter on MRI (p < 0.001). The AUC for the relative reduction in SUVmax on PET/CT was 0.78 (95% CI 0.68-0.88), and for the relative reduction in tumour diameter at late enhancement on MRI was 0.79 (95% CI 0.70-0.89). The AUC increased to 0.90 (95% CI 0.83-0.96) in the final multivariate model with PET/CT, MRI and breast cancer subtype combined (p = 0.012)., Conclusion: PET/CT and MRI showed comparable value for monitoring response during NAC. Combined use of PET/CT and MRI had complementary potential. Research with more patients is required to further elucidate the dependency on breast cancer subtype.

Over recent years, [18F]-fluorodeoxyglucose positron emission tomography acquired together with low dose computed tomography (FDG-PET/CT) has proven its role as a staging modality in patients with non-small cell lung cancer (NSCLC). The purpose of this review was to present the evidence to use FDG-PET/CT for response evaluation in patients with NSCLC, treated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI). All published articles from 1 November 2003 to 1 November 2013 reporting on 18F-FDG-PET response evaluation during EGFR-TKI treatment in patients with NSCLC were collected. In total 7 studies, including data of 210 patients were eligible for analyses. Our report shows that FDG-PET/CT response during EGFR-TKI therapy has potential in targeted treatment for NSCLC. FDG-PET/CT response is associated with clinical and radiologic response and with survival. Furthermore FDG-PET/CT response monitoring can be performed as early as 1-2 wk after initiation of EGFR-TKI treatment. Patients with substantial decrease of metabolic activity during EGFR-TKI treatment will probably benefit from continued treatment. If metabolic response does not occur within the first weeks of EGFR-TKI treatment, patients may be spared (further) unnecessary toxicity of ineffective treatment. Refining FDG-PET response criteria may help the clinician to decide on continuation or discontinuation of targeted treatment.

Unlabelled: The purpose of this study was to prospectively evaluate the timing of metabolic response monitoring with (18)F-FDG PET of (neoadjuvant) erlotinib treatment in patients with early-stage non-small cell lung cancer., Methods: This study was designed as an open-label phase II trial performed in 4 hospitals in The Netherlands. Patients received preoperative erlotinib (150 mg) once daily for 3 wk. Response evaluation was performed after 4-7 d and at 3 wk with (18)F-FDG PET/CT scans. Tumor (18)F-FDG uptake and changes were measured as standardized uptake values (SUVs). The metabolic response was classified on the basis of European Organization for Research and Treatment of Cancer criteria (>25% decrease in the maximum SUV) and was compared with histopathologic regression as observed in the resection specimen., Results: From December 2006 to November 2010, 60 patients with non-small cell lung cancer eligible for surgical resection were enrolled in this study. For 43 patients (18 men and 25 women), baseline (18)F-FDG PET/CT scans as well as both monitoring scans and histopathologic response monitoring were available. A partial metabolic response on (18)F-FDG PET/CT scans was observed for 10 patients (23%) after 1 wk and for 14 patients (33%) after 3 wk. Histopathologic examination revealed regression (necrosis of >50%) in 11 patients (26%). In these patients, the maximum SUV decreased by a mean of 17% within 1 wk and a mean of 31% at 3 wk. Seven patients were identified as responders within 1 wk., Conclusion: Response monitoring with (18)F-FDG PET/CT within 1 wk after the start of erlotinib treatment identified approximately 64% of histopathologic responders on the basis of European Organization for Research and Treatment of Cancer criteria., (© 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Purpose: The aim of the study was to evaluate the heterogeneity of primary tumor F-fluorodeoxyglucose ((18)F-FDG) uptake in breast cancer patients using a dedicated breast PET., Patients and Methods: A positron emission tomography/computed tomography (PET/CT) of the thorax was performed 60 min after administration of 180-240 MBq of (18)F-FDG in patients with breast cancer. Subsequently, 110 min after injection, a scan was taken with a dedicated high-resolution breast PET [MAMmography with Molecular Imaging (MAMMI)]. Both procedures were performed with the patients in the prone position. Four-point scores were used to compare the intensity (0: none; 1: mild; 2: moderate; 3: high) and heterogeneity (0: none; 1: mild; 2: moderate; 3: high) of (18)F-FDG uptake between PET/CT and MAMMI images., Results: Thirty-five patients in whom the primary tumor was visualized on both scans were included in this analysis. The mean primary tumor size was 35.1 mm (range 10-108 mm). The mean intensity score was similar on both devices (2.4 for PET/CT and 2.3 for MAMMI; P=0.439), but the mean heterogeneity score on MAMMI images was significantly higher (PET/CT 1.9 vs. MAMMI 2.3; P=0.005). MAMMI showed a higher heterogeneity score in 11 (31%) of 35 patients, especially in tumors with moderate or high intensity. Significantly higher heterogeneity scores on both PET/CT and MAMMI were seen in large tumors (P=0.005 and 0.014, respectively) and in tumors with high intensity scores (P=0.012 and P<0.001, respectively)., Conclusion: Heterogeneous tumor (18)F-FDG uptake in breast cancer is frequently observed, particularly in large tumors with intense (18)F-FDG uptake. It is more often seen on MAMMI PET than on conventional PET/CT. Although the observed heterogeneity should be proven histopathologically, this finding offers a rationale for (18)F-FDG-guided biopsies.

Background: Sentinel node (SN) biopsy in penile cancer is typically performed using a combination of radiocolloid and blue dye. Recently, the hybrid radioactive and fluorescent tracer indocyanine green (ICG)-(99m)Tc-nanocolloid was developed to combine the beneficial properties of both radio-guidance and fluorescence imaging., Objective: To explore the added value of SN biopsy using ICG-(99m)Tc-nanocolloid in patients with penile carcinoma., Design, Setting, and Participants: Sixty-five patients with penile squamous cell carcinoma were prospectively included (January 2011 to December 2012). Preoperative SN mapping was performed using lymphoscintigraphy and single-proton emission computed tomography supplemented with computed tomography (SPECT/CT) after peritumoural injection of ICG-(99m)Tc-nanocolloid. During surgery, SNs were initially approached using a gamma probe, followed by patent blue dye and/or fluorescence imaging. A portable gamma camera was used to confirm excision of all SNs., Surgical Procedure: Patients underwent SN biopsy of the cN0 groin and treatment of the primary tumour., Outcome Measurements and Statistical Analysis: The number and location of preoperatively identified SNs were documented. Intraoperative SN identification rates using radio- and/or fluorescence guidance were assessed and compared with blue dye. Statistical evaluation was performed using a two-sample test for equality of proportions with continuity correction., Results and Limitations: Preoperative imaging after injection of ICG-(99m)Tc-nanocolloid enabled SN identification in all patients (a total of 183 SNs dispersed over 119 groins). Intraoperatively, all SNs identified by preoperative SN mapping were localised using combined radio-, fluorescence-, and blue dye guidance. Fluorescence imaging enabled visualisation of 96.8% of SNs, while only 55.7% was stained by blue dye (p<0.0001). The tissue penetration of the fluorescent signal, and the rapid flow of blue dye limited the detection sensitivity. A tumour-positive SN was found in seven patients., Conclusions: ICG-(99m)Tc-nanocolloid allows for both preoperative SN mapping and combined radio- and fluorescence-guided SN biopsy in penile carcinoma patients and significantly improves optical SN detection compared with blue dye., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: The management of regional nodes of penile squamous cell carcinoma has changed with time due to improved knowledge about diagnosis and treatment. To determine whether changes in the treatment of regional nodes have improved survival, we compared contemporary 5-year cancer specific survival of patients with squamous cell carcinoma of the penis with that of patients in previous cohorts., Materials and Methods: In an observational cohort study of 1,000 patients treated during 56 years 944 were eligible for analysis. Tumors were staged according to the 2009 TNM classification, and patients were divided into 4 cohorts of 1956 to 1987, 1988 to 1993, 1994 to 2000 and 2001 to 2012, reflecting changes in clinical practice regarding regional nodes. Kaplan-Meier survival curves with the log rank test and Cox proportional hazards modeling were used to examine trends in 5-year cancer specific survival., Results: The 5-year cancer specific survival of patients with cN0 disease treated between 2001 and 2012 was 92% compared to 89% (1994 to 2000), 78% (1988 to 1993) and 85% (1956 to 1987). The 5-year cancer specific survival improved significantly since 1994, the year dynamic sentinel node biopsy was introduced, at 91% (1994 to 2012) vs 82% (1956 to 1993) (p = 0.021). This conclusion still holds after adjustment for pathological T stage and grade of differentiation (HR 2.46, p = 0.01). Extranodal extension, number of tumor positive nodes and pelvic involvement in node positive (pN+) cases were associated with worse 5-year cancer specific survival., Conclusions: Despite less surgery being performed on regional nodes, 5-year cancer specific survival has improved in patients with cN0 disease. The number of tumor positive nodes, extranodal extension and pelvic involvement were highly associated with worse cancer specific survival in patients with pN+ disease. In this group other treatment strategies are needed as no improvement was observed., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to assess the accuracy of 18F-FDG PET/CT in T1 breast cancer regarding visualization of the primary tumor and the detection of locoregional and distant metastases., Methods: Sixty-two women with invasive T1 breast cancer underwent a PET/CT. Image acquisition of the thorax was done in prone position with hanging breasts, followed by whole-body scanning in supine position. Primary tumor FDG uptake was evaluated and compared with clinical and histopathological characteristics. Presence of locoregional and distant metastases was assessed and compared with conventional imaging procedures., Results: The primary tumor was visible with PET/CT in 54 (87%) of 62 patients, increasing from 59% (10/17) in tumors ≤ 10 mm to 98% (44/45) in tumors over 10 mm. All triple negative and HER2-positive tumors and 40/48 (83%) ER-positive/HER2-negative tumors were visualized. Sensitivity and specificity of PET/CT in the detection of axillary metastases were 73% and 100%, respectively. PET/CT depicted periclavicular nodes in two patients. Of 12 distant lesions, one was confirmed to be a lung metastasis, three were false positive, and eight were new primary proliferative lesions., Conclusion: Using optimal imaging acquisition, the majority of T1 breast carcinomas can be visualized with PET/CT. Specificity in the detection of axillary metastases is excellent, but sensitivity appears to be limited. Additional whole body imaging has a low yield in this specific patient group.

Purpose: To investigate the value of response monitoring in both the primary tumour and axillary nodes on sequential PET/CT scans during neoadjuvant chemotherapy (NAC) for predicting complete pathological response (pCR), taking the breast cancer subtype into account., Methods: In 107 consecutive patients 290 PET/CT scans were performed at baseline (PET/CT1, 107 patients), after 2 - 3 weeks of chemotherapy (PET/CT2, 85 patients), and after 6 - 8 weeks (PET/CT3, 98 patients). The relative changes in SUVmax (from baseline) of the tumour and the lymph nodes and in both combined (after logistic regression), and the changes in the highest SUVmax between scans (either tumour or lymph node) were determined and their associations with pCR of the tumour and lymph nodes after completion of NAC were assessed using receiver operating characteristic (ROC) analysis., Results: A pCR was seen in 17 HER2-positive tumours (65 %), 1 ER-positive/HER2-negative tumour (2 %), and 16 triple-negative tumours (52 %). The areas under the ROC curves (ROC-AUC) for the prediction of pCR in HER2-positive tumours after 3 weeks were 0.61 for the relative change in tumours, 0.67 for the combined change in tumour and nodes, and 0.72 for the changes in the highest SUVmax between scans. After 8 weeks equivalent values were 0.59, 0.42 and 0.64, respectively. In triple-negative tumours the ROC-AUCs were 0.76, 0.84 and 0.76 after 2 weeks, and 0.87, 0.93 and 0.88 after 6 weeks, respectively., Conclusion: In triple-negative tumours a PET/CT scan after 6 weeks (three cycles) appears to be optimally predictive of pCR. In HER2-positive tumours neither a PET/CT scan after 3 weeks nor after 8 weeks seems to be useful. The changes in SUVmax of both the tumour and axillary nodes combined correlates best with pCR.

Purpose: The accurate harvesting of a sentinel node in breast cancer includes a sequence of procedures with components from different medical specialities, including nuclear medicine, radiology, surgical oncology and pathology. The aim of this document is to provide general information about sentinel lymph node detection in breast cancer patients., Methods: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the European Association of Nuclear Medicine (EANM) have written and approved these guidelines to promote the use of nuclear medicine procedures with high quality. The final result has been discussed by distinguished experts from the EANM Oncology Committee, the SNMMI and the European Society of Surgical Oncology (ESSO)., Conclusion: The present guidelines for nuclear medicine practitioners offer assistance in optimizing the diagnostic information from the SLN procedure. These guidelines describe protocols currently used routinely, but do not include all existing procedures. They should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary.

Purpose: To define the correlation between the core biopsy location and the area with highest metabolic activity on 18F-FDG PET/CT in stage II-III breast cancer patients before neoadjuvant chemotherapy. Also, we would like to select a subgroup of patients in which PET/CT information may optimize tumor sampling., Methods: A PET/CT in prone position was acquired in 199 patients with 203 tumors. The distance and relative difference in standardized uptake value (SUV) between core biopsy localization (indicated by a marker) and area with highest degree of FDG uptake were evaluated. A distance ≥ 2 cm and a relative difference in SUV ≥ 25% were considered clinically relevant and a combination of both was defined as non-correspondence. Non-correspondence for different tumor characteristics (TNM stage, lesion morphology on MRI and PET/CT, histology, subtype, grade, and Ki-67) was assessed., Results: Non-correspondence was found in 28 (14%) of 203 tumors. Non-correspondence was significantly associated with T-stage, lesion morphology on MRI and PET/CT, tumor diameter, and histologic type. It was more often seen in tumors with a higher T-stage (p = 0.028), diffuse (non-mass) and multifocal tumors on MRI (p = 0.001), diffuse and multifocal tumors on PET/CT (p<0.001), tumors >3 cm (p<0.001), and lobular carcinomas (p<0.001). No association was found with other features., Conclusion: Non-correspondence between the core biopsy location and area with highest FDG uptake is regularly seen in stage II-III breast cancer patients. PET/CT information and possibly FDG-guided biopsies are most likely to improve pretreatment tumor sampling in tumors >3 cm, lobular carcinomas, and diffuse and multifocal tumors., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Response monitoring with MRI during neoadjuvant chemotherapy (NAC) in breast cancer is promising, but knowledge of breast cancer subtype is essential. The aim of the present study was to evaluate the relevance of breast cancer subtypes for monitoring of therapy response during NAC with 18F-FDG PET/CT., Methods: Evaluation included 98 women with stages II and III breast cancer. PET/CTs were performed before and after six or eight weeks of NAC. FDG uptake was quantified using maximum standardized uptake values (SUVmax). Tumors were divided into three subtypes: HER2-positive, ER-positive/HER2-negative, and triple negative. Tumor response at surgery was assessed dichotomously (presence or absence of residual disease) and ordinally (breast response index, representing relative change in tumor stage). Multivariate regression and receiver operating characteristic (ROC) analyses were employed to determine associations with pathological response., Results: A (near) complete pathological response was seen in 19 (76%) of 25 HER2-positive, 7 (16%) of 45 ER-positive/HER2-negative, and 20 (71%) of 28 triple negative tumors. Multivariate regression of pathological response indicated a significant interaction between change in FDG uptake and breast cancer subtype. The area under the ROC curve was 0.35 (0.12-0.64) for HER2-positive, 0.90 (0.76-1.00) for ER-positive/HER2-negative, and 0.96 (0.86-1.00) for triple negative tumors. We found no association between age, stage, histology, or baseline SUVmax and pathological response., Conclusion: Response monitoring with PET/CT during NAC in breast cancer seems feasible, but is dependent on the breast cancer subtype. PET/CT may predict response in ER-positive/HER2-negative and triple negative tumors, but seems less accurate in HER2-positive tumors., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

In breast cancer patients treated with neoadjuvant chemotherapy (NAC) the number of tumor-positive nodes can no longer reliably be determined. Furthermore, ultrasound (US) seems suboptimal for the detection of N3-disease. Therefore we assessed the proportion of breast cancer patients treated with NAC in which pre-chemotherapy 18F-FDG PET/CT detected ≥4 axillary nodes or occult N3-disease, upstaging nodal status and changing risk estimation for locoregional recurrence (LRR). Conventional regional staging consisted of US with fine needle aspiration and/or sentinel lymph node biopsy. Patients were classified as low-risk (cT2N0), intermediate-risk (cT0N1, cT1N1, cT2N1, cT3N0), or high-risk (cT3N1, cT4, cN2-3) for LRR. The presence and number of FDG-avid nodes were evaluated and the proportion of patients that would be upstaged by PET/CT, based on detection of ≥4 FDG-avid axillary nodes defined as cN2(4+) or occult N3-disease, was calculated. In total, 87 of 278 patients were considered high-risk based on conventional staging. PET/CT detected occult N3-disease in 5 (11 %) of 47 low-risk patients. In 144 intermediate-risk patients, PET/CT detected ≥4 FDG-avid nodes in 24 (17 %) patients and occult N3-disease in 22 (15 %) patients, thereby finally upstaging 38 (26 %) of intermediate-risk patients. Of 43 (23 %) upstaged patients, 18 were ypN0, 12 were ypN1, and 13 were ypN2-3. Pre-chemotherapy PET/CT is valuable for selection of breast cancer patients at high risk for LRR. In our population, 23 % of patients treated with NAC were upstaged to the high-risk group based on PET/CT information, potentially benefiting from regional radiotherapy.

Background: Radioguided occult lesion localization (ROLL) with technetium-99 m colloid (ROLL-(99m)Tc) is commonly used to perform breast-conserving surgery in patients with nonpalpable breast tumors. Radioactive seed localization is a relatively new technique that localizes the tumor with a radioactive iodine-125 ((125)I) seed. The feasibility and outcome of these techniques after neoadjuvant systemic treatment has not been widely investigated., Methods: All patients treated with neoadjuvant systemic treatment between 2007 and 2010 in the Netherlands Cancer Institute who underwent breast-conserving surgery with the ROLL-(99m)Tc technique (n = 83) or with (125)I seed localization (n = 71) were analyzed. The weight of the resected specimen, the margins, and the percentage of patients requiring a second surgical intervention as a result of positive margins were assessed., Results: Patient and tumor characteristics and systemic treatment regimens were comparable between both groups. The median weight of the resected specimen (53 vs. 48 g), the median smallest margin (3.5 vs. 3.0 mm), and the risk for additional surgery for incomplete resections (7 vs. 8 %) did not differ significantly between patients treated with the ROLL-(99m)Tc technique and (125)I seed localization., Conclusions: The ROLL-(99m)Tc technique and (125)I seed localization demonstrate comparable results when used to perform breast-conserving surgery after neoadjuvant systemic treatment. Because (125)I seed localization does not require additional radiological localization shortly before surgery, it simplifies surgery scheduling. Therefore, we prefer (125)I seed localization to perform breast-conserving surgery after neoadjuvant systemic treatment.

Background: If all initially node-positive patients undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC), overtreatment may occur in patients with complete response. Positron emission tomography-computed tomography (PET/CT) during NAC may predict axillary response and select patients appropriate for less invasive treatment after NAC. We evaluated the value of sequential (18)F fluorodeoxyglucose (FDG) PET/CTs during NAC for axillary response monitoring in stage II-III breast cancer., Methods: A total of 219 PET/CTs were performed in 80 patients with cytology-proven, node-positive disease at baseline (PET/CT1, n = 80) and twice during NAC (PET/CT2 n = 62, PET/CT3, n = 77). The relative changes in maximum standardized uptake value (SUVmax) of axillary nodes were examined for their ability to assess pathological response. All patients underwent ALND after chemotherapy, and complete axillary response (pCR), defined as absence of isolated tumor cells and of micro- and macrometastases, served as the reference standard., Results: A total of 32 (40 %) patients experienced axillary pCR. The relative decrease in SUVmax was significantly higher in patients with pCR than in those without, both on PET/CT2 (p < 0.001) and PET/CT3 (p = 0.025). The area under the receiver operating characteristic curve values for PET/CT2 and PET/CT3 were 0.80 (95 % confidence interval 0.68-0.92) and 0.65 (95 % confidence interval 0.52-0.79), respectively. A relative decrease of ≥60 % on PET/CT2 had an excellent specificity (35 of 37, 95 %), a high positive predictive value (12 of 14, 86 %), and a sensitivity of 48 %-that is, it accurately identified histologic pCR in 12 of 25 patients with disease that responded to therapy., Conclusions: (18)F-FDG PET/CT early during NAC is useful for axillary response monitoring in cytology-proven node-positive breast cancer because it identifies pathological response, thus permitting ALND to be spared.

To provide surgeons with optimal guidance during interventions, it is crucial that the molecular imaging data generated in the diagnostic departments finds its way to the operating room. Sentinel lymph node (SLN) biopsy provides a textbook example in which molecular imaging data acquired in the department of nuclear medicine guides the surgical management of patients. For prostate cancer, in which SLNs are generally located deep in the pelvis, procedures are preferably performed via a (robot-assisted) laparoscopic approach. Unfortunately, in the laparoscopic setting the senses of the surgeon are reduced. This topical review discusses technologic innovations that can help improve surgical guidance during SLN biopsy procedures.

The lymphatic drainage of cutaneous melanomas located on the upper trunk is often complex and sometimes follows an unexpected pattern. Occasionally, even direct drainage to cervical lymph nodes is seen. In this case series, 3 patients with lymphatic drainage to the neck derived from melanomas located over the manubrium sterni are described. There appears to be a restricted area that involves the manubrium sterni from which lymphatic drainage to different cervical node basins appears more frequent. SPECT/CT was helpful in visualizing these patterns and for the localization of the sentinel nodes.

Purpose: The development of targeted therapy has introduced new options to improve treatment outcome in selected patients. The objective of this prospective study was to investigate the safety of preoperative erlotinib treatment and the (in vivo) response in patients with early-stage resectable non-small-cell lung cancer (NSCLC)., Patients and Methods: This study was designed as an open-label phase II trial, performed in four hospitals in the Netherlands, according to a Simon's minimax two-stage procedure. Initially, operable patients with early-stage NSCLC (n = 15) were entered from an enriched population (never-smoker, female sex, nonsquamous histology, or Asian ethnicity); thereafter, unselected patients were included to a total of N = 60. Patients received preoperative erlotinib 150 mg once daily for 3 weeks. Response to treatment was evaluated using [18F] fluorodeoxyglucose positron emission tomography (PET) and computed tomography (CT) scans during treatment and histologic examination of the resection specimen. Primary end points were toxicity and pathologic response., Results: Sixty patients were included. Seven patients stopped treatment prematurely (12%). Skin toxicity was present in 37 patients (62%), and diarrhea was present in 21 patients (35%). PET evaluation revealed metabolic response (> 25% standardized uptake value decrease) in 16 patients (27%); CT evaluation using Response Evaluation Criteria in Solid Tumors (RECIST) showed response in three patients (5%). At surgery, no unexpected complications occurred. Pathologic examination showed more than 50% necrosis in 14 patients (23%), of whom three (5%) had more than 95% tumor necrosis. The response rate in the enriched population was 34% (10 of 29 patients)., Conclusion: According to predefined criteria, neoadjuvant erlotinib has low toxicity and sufficient activity to deserve further testing in future studies in an enriched population.