Synchronous Treatment of Breast Cancer Hepatic Metastases by Transarterial Radioembolization and Radiofrequency Thermoablation: A Case Report.

ABSTRACT: In a 51-year-old woman affected by breast cancer, hepatic recurrence of disease was managed by concurrent 90 Y-labeled glass microsphere embolization (transarterial radioembolization) and radiofrequency thermoablation. Intention-to-treat target, candidate to radioembolization, was in the IV hepatic segment; another lesion, managed with radiofrequency thermoablation, was in the VI-VII hepatic segment. Concomitant correction of a duodenocephalopancreatic shunting was performed as well. Thermoablation did not interfere with distribution of 99m Tc-macroaggregated albumin and 90 Y-labeled microspheres to the target and healthy liver. At our knowledge, this is the first report that combines 2 locoregional procedures in different hepatic segments on the same day.

99mTc-Tilmanocept performance for sentinel node mapping in breast cancer, melanoma, and head and neck cancer: a systematic review and meta-analysis from a European expert panel.

PURPOSE: Although multiple radiopharmaceuticals are currently available for sentinel node (SN) biopsy, 99mTc-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 99mTc-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 99mTc-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 99mTc-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: 99mTc-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 99mTc-tilmanocept is superior to other radiotracers used in clinical routine.

Dose-response Analysis in Hepatic Tumors Treated with 90Y-TARE According to a Personalized Dosimetric Workflow: Preliminary Results.

BACKGROUND: Transarterial Radioembolization (TARE) is a widespread radiation therapy for unresectable hepatic lesions, but a clear understanding of the dose-response link is still missing. The aim of this preliminary study is to investigate the role of both dosimetric and clinical parameters as classifiers or predictors of response and survival for TARE in hepatic tumors and to present possible response cut-off. METHODS: 20 patients treated with glass or resin microspheres according to a personalized workflow were included. Dosimetric parameters were extracted from personalized absorbed dose maps obtained from the convolution of 90Y PET images with 90Y voxel S-values. RESULTS: D95 ≥ 104 Gy and tumor mean absorbed dose MADt ≥ 229 Gy were found to be optimal cut-off values for complete response, while D30 ≥ 180 Gy and MADt ≥ 117 Gy were selected as cut-off values for at least partial response and predicted better survival. Clinical parameters Alanine Transaminase (ALT) and Model for End-Stage Liver Disease (MELD) didn't show sufficient classification capability for response or survival. CONCUSION: These preliminary results highlight the importance of an accurate dosimetric evaluation and suggest a cautious approach when considering clinical indicators. Dosimetric cut-off values could be a support tool in both planning and post-treatment phases. Larger multi-centric randomized trials, with standardized methods regarding patient selection, response criteria, Regions of Interest definition, dosimetric approach and activity planning are needed to confirm these promising results.

Selective Axillary Dissection after Neoadjuvant Chemotherapy in Patients with Lymph-Node-Positive Breast Cancer (CLYP Study): The Radio-Guided Occult Lesion Localization Technique for Biopsy-Proven Metastatic Lymph Nodes.

(1) Background: To help to refine the accuracy of sentinel lymph node biopsy (SLNB) in breast cancer (BC) patients with biopsy-proven nodal disease prior to neoadjuvant chemotherapy (NACT), a method of marking the biopsy-proven positive LN at diagnosis to enable its removal during surgery was proposed. The aim of this study was to evaluate the accuracy of the Radio-Guided Occult Lesion Localization (ROLL) technique of biopsy-proven metastatic LN in nodal staging after NACT among node-positive BC patients. (2) Methods: Patients with invasive BC and biopsy-proven axillary metastases receiving NACT were enrolled. A clip marker was placed on the sampled LN (clipped lymph node, CLN) before NACT. Before surgery, the ROLL procedure (radioactive tracer injection into CLN under ultrasound guidance) was performed, and the CLN was surgically resected. The correspondence between the CLNs and SLNs was evaluated. The pathologic findings of the CLNs and SLN(s) were compared with remaining axillary nodes at ALND to determine false negative rates (FNRs). (3) Results: Seventy-two patients were analyzed. Surgery successfully identified the CLN in 70/72 procedures (97.2%). For 60/72 patients who underwent ALND, the FNRs dropped from 19.35% for SLNB to 3.13% for CLN biopsy. (4) Conclusions: The ROLL procedure got CLNs is accurate in axillary nodal staging after NACT in node-positive BC patients at diagnosis.

PET/CT with Fibroblast Activation Protein Inhibitors in Breast Cancer: Diagnostic and Theranostic Application-A Literature Review.

Growing studies have recently reported on the promising application of radiolabeled-fibroblast activation protein inhibitors (FAPIs) as diagnostic and therapeutic agents in various oncological populations. To exclusively evaluate the current evidence on the diagnostic and therapeutic role of FAPI radiotracers in patients with breast cancer (BC), a narrative review of the available literature was performed. A search algorithm from PubMed/MEDLINE, based on the combination of "PET" OR "positron emission tomography" and "FAPI" and "cancer", with a last update in February 2022, was applied. From 233 identified articles, 33 studies conducted in BC patients and with available data on PET imaging or radiolabeled-FAPI therapy were finally considered, for a total of 191 patients. Despite some clinical and methodological heterogeneity among the reviewed articles, 68Ga-FAPI PET/CT emerges as a valuable diagnostic tool in BC patients both at staging and restaging, also demonstrating several technical advantages and an overall better performance than 18F-FDG, especially in histotypes with well-known low 18F-FDG avidity. Moreover, although with still limited clinical evidence in BC, radiolabeled FAPIs emerge as promising therapeutic agents in a theranostic perspective, increasing the possibility of more personalized treatments. From these results, future research directions on FAPI radiotracers application in BC patients are suggested.

Lymphatic mapping and sentinel node biopsy in vulvar melanoma: the first multicenter study and systematic review.

OBJECTIVE: This multicenter study aimed to investigate the role of preoperative lymphatic mapping and sentinel node biopsy (SNB) as well as the impact of negative SNB on loco-regional control and survival in vulvar melanoma patients with clinically negative nodes (cN0). METHODS: Patients who had a proven vulvar melanoma with a Breslow thickness of 1-4 mm, cN0 and underwent a preoperative lymphatic mapping followed by SNB between July 2013 and March 2021 were retrospectively included. Groin recurrence and mortality rate were calculated as absolute and relative frequency. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method. We provided a systematic review, searching among PubMed/Medline and Embase libraries. A total of 6 studies were identified (48 patients). RESULTS: A total of 18 women were included. Preoperative planar images showed 51 SNs in 28 groins. Additional SPECT/CT images were acquired in 5/18 cases; SNs were identified pre- and intra-operatively in all cases. A total of 65 SNs were excised from 28 groins. A total of 13/18 (72.2%) patients (21/28 groins, 75%) had negative SNs with no groin recurrences and 12/13 (92.3%) were still alive at last follow-up. Five out of the 18 (27.8%) patients (7/28 groins, 25%) had positive SNs, 2/5 (40%) patients died of cancer after 26.2 and 33.8 months, respectively. The median DFS and OS for the entire cohort were 17.9 months (95% CI, 10.3-19.9) and 65.0 months (95% CI, 26.2-infinite), respectively. The probability of DFS and OS at 3 years were 15.5% (95% CI, 2.6-38.7) and 64.3% (95% CI, 15.5-90.2), respectively. CONCLUSIONS: The use of preoperative lymphatic mapping followed by SNB permits a precise and minimally invasive surgical approach in cN0 vulvar melanoma patients. Negative SNB is associated with low risk of groin relapse and good survival.

18F-FDG PET/CT concurrent with first radioiodine post-therapeutic scan in high risk differentiated thyroid cancer: a useful tool or just an expensive diversion?

BACKGROUND: Aim of the present study was to evaluate the clinical impact of fluorine-18F-fluorodeoxyglucose PET/CT (18F-FDG-PET/CT) concurrent with post-therapeutic whole-body radioiodine scan (TxWBS) after first radioiodine (RAI) treatment in patients with high-risk differentiated thyroid carcinoma (DTC). METHODS: This was a retrospective, single-center study including 39 patients with DTC (22 females, 17 males, median age 54; IQR: 35-60 years, 87% papillary thyroid cancer, 13% follicular thyroid cancer). All patients underwent 18F-FDG-PET/CT and RAI treatment, both performed off L-T4 about 3 months after total thyroidectomy. TxWBS was obtained 3 days afterwards using planar technique and SPECT/CT of neck and thorax regions. Semiquantitative analysis was performed on positive 18F-FDG-PET/CT scans to assess SUVmax, SUVratio, MTV and TLG values in target lesions (hottest 18F-FDG-positive lesion present in each patient). Receiver operating characteristics (ROC) curve analysis was obtained to establish a cut-off point for SUVmax able to predict the presence of RAI nonavid lesions. Univariate and multivariate analyses were executed to find out predictive factors for abnormal 18F-FDG-PET/CT imaging. RESULTS: In 11 (28%) patients 18F-FDG-PET/CT and TxWBS were both negative and in 9 (23%) both positive, showing loco-regional or distant metastases. In 14 patients (36%) 18F-FDG-PET/CT showed more lesions than TxWBS, while in 5 (13%) patients more lesions were present at TxWBS than 18F-FDG-PET/CT. Overall, 23 patients (59%) showed 18F-FDG avid lesions and 18F-FDG-PET/TC changed the management in 14 (36%), including the choice to perform RAI therapy with higher activities than expected, lymph-node dissection for loco-regional metastases, direct therapy for solitary bone metastases. Through ROC curve analysis, a value superior to 7.25 of SUVmax was able to predict the presence of RAI non-avid lesion at TxWBS. Serum stimulated thyroglobulin and extranodal invasion resulted to be risk factors for abnormal 18F-FDG-PET/CT imaging. However, only extranodal invasion turned out to be an independent risk factor for abnormal 18F-FDG-PET/CT. CONCLUSIONS: The present study demonstrated the clinical value of RAI-concurrent 18F-FDG-PET/CT in patients with high-risk DTC. However, some questions remain open, including the pretherapeutic thyroglobulin level to use as indication to 18F-FDG-PET/CT and the predictive value of 18F-FDG-PET/CT semiquantitative parameters.

Multidisciplinary ocular and periocular cancers meetings: implementation in a tertiary referral center and analysis over a 12-months period.

PURPOSE: The complexity of multimodal approaches in cancer management has lately led to the establishment of multidisciplinary tumor boards (MDTBs) to define targeted, patient-centered treatment strategies. However, few data are available regarding the application of this approach in Ocular Oncology. Hereby, the Authors analyze the implementation and outcomes of a trained MDTB in a tertiary ocular oncology referral center. METHODS: A retrospective descriptive analysis of MDTB meetings discussing patients with ocular and periocular cancers, over a 12-months period, was carried out. Data were grouped by main site involved, topics discussed and final clinical decisions therefore taken. Meetings were held by a constant 'Core team' or - when required - by a broader 'Extended team'. RESULTS: During the observational period 86 cases were discussed. In 27 patients ocular surface tissues were involved (31%), in 25 patients orbital tissues (29%), in 22 patients eyelids (26%), and in 12 patients intraocular tissues (14%). In 13 cases (15%) naïve or referred new patients, in 34 cases (40%) imaging or histopathologic reports and in 39 cases (45%) treatment plans were discussed. Regarding final decisions, a treatment plan was scheduled in 47 cases (55%) and a diagnostic ascertainment was required in 27 patients (31%); locally advanced and/or systemic diseases were referred or teamed up with other specialists in 12 cases (14%). CONCLUSIONS: Ocular Oncology multidisciplinary team, by sharing expertise of different specialists, ensures a comprehensive evaluation of patients improving the accuracy of diagnosis and staging upon which planning a proper treatment. Further studies are needed to assess if this approach may also improve the outcomes and prognosis of patients.

Induction Regimen in High-Risk Neuroblastoma: A Pilot Study of Highly Effective Continuous Exposure of Tumor Cells to Radio-Chemotherapy Sequence for 1 Month. The Critical Role of Iodine-131-Metaiodobenzylguanidine.

The prognosis of high-risk neuroblastoma (NB) continues to be poor. The early development of resistance often leads to disease recurrence. In the present study, an innovative induction regimen, including an intensive initial radio-chemotherapy sequence based on the use of iodine-131-metaiodobenzylguanidine (131-I-MIBG), was investigated. The duration of the regimen lasted only one month. Fifteen newly diagnosed patients aged >18 months with high-risk NB were treated with cisplatin, etoposide, cyclophosphamide, and vincristine, followed on day 10 by 131-I-MIBG (dose: 12−18.3 mCi/kg). Cisplatin and vincristine were administered on day 20 and 21 followed by the re-administration of vincristine, cyclophosphamide, and doxorubicin on day 29 and 30. Non-hematologic toxicity was not observed. Moderate hematologic toxicity was present probably attributable to chemotherapy. The evaluation of response was performed approximately 50 days after the initiation of treatment, yielding four complete responses, eight very good partial responses, one partial response, and two non-responses. Importantly, a complete metastatic response was achieved in 87% of patients. The present pilot study, which includes 131-I-MIBG, allows for a highly effective continuous exposure of tumor cells to both chemotherapy and radiotherapy. Furthermore, early high-dose chemotherapy followed by stem cell rescue may achieve high levels of tumor cell clearance and improve the prognosis of high-risk NB.

PSMA Radioligand Uptake as a Biomarker of Neoangiogenesis in Solid Tumours: Diagnostic or Theragnostic Factor?

Due to its overexpression on the surface of prostate cancer cells, prostate-specific membrane antigen (PSMA) is a relatively novel effective target for molecular imaging and radioligand therapy (RLT) in prostate cancer. Recent studies reported that PSMA is expressed in the neovasculature of various types of cancer and regulates tumour cell invasion as well as tumour angiogenesis. Several authors explored the role of diagnostic and therapeutic PSMA radioligands in various malignancies. In this narrative review, we describe the current status of the literature on PSMA radioligands' application in solid tumours other than prostate cancer to explore their potential role as diagnostic or therapeutic agents, with particular regard to the relevance of PSMA radioligand uptake as neoangiogenetic biomarker. Hence, a comprehensive review of the literature was performed to find relevant articles on the applications of PSMA radioligands in non-prostate solid tumours. Data on the general, methodological and clinical aspects of all included studies were collected. Forty full-text papers were selected for final review, 8 of which explored PSMA radioligand PET/CT performances in gliomas, 3 in salivary gland malignancies, 6 in thyroid cancer, 2 in breast cancer, 16 in renal cell carcinoma and 5 in hepatocellular carcinoma. In the included studies, PSMA radioligand PET showed promising performance in patients with non-prostate solid tumours. Further studies are needed to better define its potential role in oncological patients management, especially in those undergoing antineoangiogenic therapies, and to assess the efficacy of PSMA-RLT in this clinical context.

Parathyroid Carcinoma All-In-One, a Rare Life-Threatening Case With Multiple Systemic Manifestations: Case Report and Review of the Literature.

Parathyroid carcinoma (PC) is an extremely rare disease. Although it may occasionally occur in genetic syndromes, it is more often sporadic. It is usually associated with a consistent secretion of PTH, causing severe hypercalcemia and potentially all clinical conditions due to primary hyperparathyroidism. Management of PC can be challenging: some clinical, biochemical, and radiological features may be useful, but the final diagnosis of malignancy strictly relies on histological criteria. To date, radical surgery is the first-choice treatment and is the only effective therapy to control hypercalcemia and other clinical manifestations. On the other hand, chemo- or radiotherapy, local treatments, or novel drugs should be reserved for selected cases. We report an exceptionally unusual case of life-threatening PC, associated with several systemic manifestations: moderate pancreatitis, portal thrombosis, kidney stones, brown tumors, osteoporosis, hungry bone syndrome (HBS), chondrocalcinosis, neuropathy, and depression. The clinical case also represents an opportunity to provide a review of the recent literature, associated with a complete evaluation of the main diagnostic and therapeutic approaches.

Radiation exposure of the operators in the preparation and administration of yttrium-90 microspheres in the treatment of malignant hepatic lesions: What is the risk?

Liver radioembolization is an emerging treatment against liver primary and secondary tumours. The whole procedure of radioembolization involves different health care specialists with different expertise. During the fractionation and infusion phases, the personnel manipulates high activities of 90Y. In our centre, the number of radioembolization treatments per year is increasing; the aim of this study is to monitor the dose to the operators and to estimate the radiological risk for the operators involved in the RE. At present, two medical devices are approved: Sir-Sphere® and Therasphere™, both loaded with 90Y. The dosimeters used were TLDs placed over the fingertips, for a total of 4 dosimeters for each phase; the selected dose descriptor was Hp0.07. The study concerned 17 patients affected by malignant hepatic lesions, treated from September 2017 to March 2018. We performed 27 procedures: 10 fractionations (with Sir-Sphere®) and 17 infusions to the patients (10 with Sir-Spheres®, 7 with Theraspheres™). For fractionation phase, the average activity of each preparation was 3.34 GBq, the average value of Hp0.07 was 0.50mSv. For infusion phase, the average activity was 1.51 GBq for Sir-Sphere® and 2.10 GBq for Theraspheres™, the average value of Hp0.07 was 0.10mSv. No significant differences were found between senior (Hp0.07 = 0.08mSv) and young operators (Hp0.07 = 0.09mSv), respectively. Similarly, no significant differences were found between the right and left hand, with the same average value of Hp0.07 (0.01mSv). In conclusion, the results are encouraging, since fingertips reported doses very low. The handling of 90Y microspheres and the radioembolization procedure can be carried out under safe conditions.

SPECT/CT and fusion ultrasound to target the efferent groin lymph node for lymphatic surgery.

INTRODUCTION: Pelvic lymphadenectomy (PL) causes changes to the inguinal lymph nodes with progressive loss of immune and lymphatic pump function. Efferent lymphatic vessel-to-venous anastomosis (ELVA) has been reported to address this problem. The aim of this report was to describe the feasibility of the SPECT/CT combined with ultrasound fusion imaging (UFI) to target the groin efferent lymph node (GELN) for ELVA. PATIENTS AND METHODS: Twelve patients with lower limb lymphedema after PL were scheduled for peripheric lymphaticovenular anastomosis (LVA) combined with ELVA. All-patients were clinically ISL-stage1, with good visualization of the inguinal lymph nodes at preoperative lymphoscintigraphy. The mean patient age was 55.4 years and the mean BMI was 25.5.The mean limb circumference (MLC) was calculated before surgery and 1 year after surgery. The LymQoL-Leg questionnaire was administered before surgery and 6 months after surgery. Before surgery, the GELN was identified by SPECT/CT and its location was marked on the skin by UFI virtual navigation. Peripheric LVA sites were planned by ultrasound and indocyanine green (ICG) lymphography. Pre and postoperative MLC and LymQoL-Leg scores were compared. RESULTS: In all-patients, the SPECT/CT succeeded at detecting and targeting the GELN. In all-patients, real-time anatomical coregistration with US was feasible, and it was possible to mark on the groin skin the depth and position of the GELN on the skin at the groin. During surgery, in every patient, we found the GELN marked before surgery and performed ELVA. We also performed two or three peripheric LVAs in every patient. The mean value of MLC decreased (38.2 ± 2.13 cm vs. 36.33 ± 2.14 cm; p = .04) and the mean score of the LymQoL-Leg questionnaire improved (9.3 ± 1.7 vs. 7.7 ± 1.1; p = .02). CONCLUSION: SPECT/CT combined with UFI is feasible for the preoperative identification of GELN for ELVA.

Accumulation of 131I in Esophageal Diverticulum Diagnosed by SPECT/CT.

A 72-year-old man underwent total thyroidectomy and radioiodine remnant ablation for papillary thyroid cancer in 2016. The posttherapy whole-body scan showed uptake in the neck, classified as residual thyroid tissue. Two years later, the patient came to our observation to perform a second radioiodine therapy for high levels of thyroglobulin. The planar posttherapy scan showed a focal radioiodine area in the neck. SPECT/CT diagnosed a voluminous esophageal diverticulum located in the upper third of the esophagus. A CT performed to discover the source of thyroglobulin excluded locoregional or distant metastases and confirmed the presence of a Zenker diverticulum.

Parathyroid gland ultrasound patterns and biochemical findings after one-year cinacalcet treatment for advanced secondary hyperparathyroidism.

Cinacalcet efficacy is limited in severe secondary hyperparathyroidism (SHPT) and its effect on parathyroid gland (PTG) volume and morphology have not been sufficiently investigated. We evaluated the effect of cinacalcet treatment for one year on the laboratory parameters of calcium-phosphorus metabolism and PTG ultrasound (US) patterns in hemodialysis (HD) patients with severe SHPT and US results indicative of nodular hyperplasia. Thirteen HD patients with severe SHPT (intact parathyroid hormone >700 pg/mL), US/scintigraphic evidence of at least one PTG with a diameter >7 mm, and high surgical risk or refusal of surgery were included. The patients were treated with cinacalcet. The initial dose of 30 mg was increased up to 180 mg once daily. At baseline and after one year of cinacalcet treatment a neck US was performed, providing data on 22 parathyroid glands in eight patients. The mean diameter at baseline and at one year was 12.6 +/- 5.9 and 13.0 +/- 5.3 mm, respectively (P = 0.46). Similarly, the mean volume at baseline and at one year was 513.4 +/- 416.3 and 556.8 +/- 480.8 mm(3), respectively (P = 0.18). The US structural score remained unchanged in 16 parathyroid glands and increased in 6 (P < 0.03), while the vascular score remained unchanged in 16 parathyroid glands and decreased in 6 (P = 0.25). Thus it can be concluded that cinacalcet treatment for one year in HD patients with severe SHPT is not associated with significant changes in parathyroid gland US patterns.