Impact of the SARS-CoV2 pandemic dissemination on the management of neuroendocrine neoplasia in Italy: a report from the Italian Association for Neuroendocrine Tumors (Itanet).

INTRODUCTION: The organization of the healthcare system has significantly changed after the recent COVID-19 outbreak, with a negative impact on the management of oncological patients. The present survey reports data collected by the Italian Association for Neuroendocrine Tumors on the management of patients with neuroendocrine neoplasia (NEN) during the pandemic dissemination. METHODS: A survey with 57 questions was sent to NEN-dedicated Italian centers regarding the management of patients in the period March 9, 2020, to May 9, 2020 RESULTS: The main modification in the centers' activity consisted of decreases in newly diagnosed NEN patients (- 76.8%), decreases in performed surgical procedures (- 58%), delays to starting peptide receptor radionuclide therapy (45.5%), postponed/canceled follow-up examinations (26%), and canceled multidisciplinary teams' activity (20.8%). A low proportion of centers (< 10%) reported having to withdraw systemic anti-tumor medical treatment due to concerns about the pandemic situation, whereas PRRT was withdrawn from no patients. CONCLUSION: Although the COVID-19 outbreak induced the centers to reduce some important activities in the management of NEN patients, the Italian network was able to provide continuity in care without withdrawing anti-tumor treatment for the majority of patients.

Second Axillary Sentinel Lymph Node Biopsy for Breast Tumor Recurrence: Experience of the European Institute of Oncology.

PURPOSE: This retrospective study aimed to determine the feasibility, accuracy, and recurrence rates of lymphoscintigraphy and the new sentinel lymph node biopsy (SLNB) for patients with ipsilateral breast tumor recurrences who were treated previously with conservative surgery and had negative SLNB results. METHODS: The study was conducted at the European Institute of Oncology in Milan and included 212 patients with the diagnosis of operable local breast cancer recurrence. They had been treated previously with conservative surgery and showed negative SLNB results. They subsequently underwent additional breast surgery and a second SLNB between May 2001 and December 2011. RESULTS: Preoperative lymphoscintigraphy demonstrated at least one new axillary sentinel lymph node (SLN) in 207 patients (97.7 %), whereas no drainage was observed in five patients (2.3 %). One or more SLNs were surgically removed from 196 of the 207 patients. Isolation of SLNs from the remaining 11 patients could not be accomplished. The success rate for the SLNB was 92.5 %. Extra-axillary drainage pathways were visualized in 17 patients (8 %). The annual axillary recurrence rate after a median follow-up period of 48 months was 0.8 %, and the cumulative incidence of axillary recurrence at 5 years was 3.9 %. CONCLUSIONS: A second SLNB should be considered for patients with operable local breast tumor recurrence who underwent conservative surgery and had negative SLNB results. The procedure is technically feasible and accurate for selected patients.

New radiopharmaceutical agents for the treatment of castration-resistant prostate cancer.

Prostate cancer (PCa) is the fourth most common cancer worldwide in terms of incidence and third among male, but is becoming the most common cancer in developed countries. In many patients the disease will progress despite of castration levels of testosterone, to become castration-resistant PCa (CRPC). Nearly all patients with CRPC show bone metastases. The treatment of patients with bony metastases has dramatically changed during the past three years because of new therapeutic approaches addressed to obtain pain control, reduced skeletal morbidity, and most importantly, increased survival rate. A possible therapy can be based also on the use of radiopharmaceuticals systemically administered to slow or reverse the bone metastatic progression. In facts bone-homing radiopharmaceuticals are taken up in areas of high bone turnover, including areas with high osteoblastic activity. Recently, a bone targeting radiopharmaceutical, Radium-223 dichloride was added to this group of drugs clearly representing a new generation of radiopharmaceutical in bone therapy. Clinical trials had shown that the treatment with Ra-223 allowed the reduction of the risk of death respect to placebo. No other radiometabolic treatment achieved such result, evidentiating the disease-modifying properties of this bone-homing radiopharmaceutical. In an effort to treat patients with disseminated PCa, who became resistant to hormonal therapy, molecular targets have been recently identified. Prostate specific membrane antigen (PSMA) is one attractive target for diagnosis and therapy of metastasized PCa since its expression levels are directly correlated to androgen independence, metastasis, and progression. Gastrin-releasing peptide receptors (GRPr) are also highly overexpressed in PCa. Numerous studies suggest the possibility of a high PCa-specific signal with radiolabeled bombesin analogs targeting GRPr. Low molecular weight peptides directed against these molecular targets have been radiolabeled with positron emitting radionuclides such as 68Ga in order to improve sensitivity and specificity for detecting primary, metastatic, and recurrent PCa by PET/CT over conventional imaging techniques. Although peptide radionuclide ligand therapy studies have just initiated, the diagnostic relevance of 68Ga labeled specific tracers has already been established its clinical utility and represents a valid tool against this common and deadly cancer.

Nodal Merkel Cell Carcinoma with Unknown Primary Site and No Distant Metastasis: A Single-Center Series.

Merkel cell carcinoma (MCC) is a very rare and aggressive neuroendocrine carcinoma originating from Merkel cells, typically with a skin nodule; however, it exceptionally presents with only a basin lymph node localization, with neither a cutaneous primary site nor distant metastases. From 1996 to 2020, among patients with histologically confirmed MCC managed at a neuroendocrine neoplasm-referral center, we selected those with an exclusive nodal basin, no distant metastasis, and an unknown primary site defined by cross-sectional and physical examination. A total of 55 out of 310 patients fulfilled the selection criteria. The median age was 64 years and the majority were males. Inguinal lymph-nodes were the most common anatomic site. With a median follow-up of 4.3 years, the 5-year relapse-free survival (RFS) rate was 56.6 (95% CI 42.0-68.8%) and the 5-year cancer specific survival (CSS) rate was 68.5 (95% CI 52.8-79.9%) for the whole population. The 36 patients (65.5%) undergoing lymphadenectomy (LND) + radiotherapy (RT) ± chemotherapy had a 5-year RFS rate of 87.2% (95% CI 65.5-95.7%) and a 5-year CSS rate of 90.5% (95% CI 67.0-97.5), which were better than those receiving LND alone. In a multivariable analysis, the survival benefit for LND + RT remained significant. Results from one of the largest single-center series of nMCC-UP suggest that a curative approach including RT can be effective, similar to what is observed for stage IIIB MCC. Multicentric studies with homogenous populations should be carried out in this controversial clinical entity, to minimize the risk of biases and provide robust data.

Prognostic value of PET parameters in patients with pleomorphic lung cancer: Results from a single institution.

OBJECTIVES: Pleomorphic lung carcinoma (PLC) is a rare histotype of non-small cell lung cancer (NSCLC) characterized by aggressive clinical course, poor response to therapy and poor prognosis. Therefore, aim of our study is to analyze with 18F-FDG PET/CT a subset of patients affected by PLC to evaluate their metabolic characteristics in terms of SUVmax, MTV and TLG, in order to correlate them with overall survival (OS) and disease-free survival (DFS). MATERIAL AND METHODS: We retrospectively analyzed 49 consecutive patients with histologically defined PLC occurred to our Institution between 2003 and 2014. All patients underwent F18-FDG PET-CT before surgery and primary tumor was automatically segmented using an isocontour threshold method. SUV threshold for tumor segmentation was defined as the 41 % of lesion SUVmax. Total volume of the segmented VOI (MTV, centimeters cubed) and average SUV (SUVavg, grams per milliliter) in the segmented VOI were measured. RESULTS: In our population men were significantly more affected than women (42:7). According to Youden criteria, SUVmax, MTV41 and TLG41 best cut-off values to predict 2-year mortality were, 18.95, 27.89 and 290.45, respectively, with TLG41 showing best specificity (85 %) and positive predictive value (82.4 %). As concerning 2-year recurrence, SUVmax, MTV41 and TLG41 best cut-off values were 10.08, 27.89 and 134.85, with SUVmax showing best sensitivity (96.7 %) and negative predictive value (85.7 %). ROC curves confirmed that SUVmax, MTV41 and TLG41 were equally accurate to predict 2-year mortality and 2-year recurrence in our population. CONCLUSION: Metabolic biomarkers such as SUVmax, MTV and TLG can be used as a prognostic index for disease progression, recurrence and death in patients with PLC, independently from other clinical/pathological prognostic elements.

Tumor-non-tumor discrimination by a ß- detector for Radio Guided Surgery on ex-vivo neuroendocrine tumors samples.

This paper provides a first insight of the potential of the ß- Radio Guided Surgery (ß--RGS) in a complex surgical environment like the abdomen, where multiple sources of background concur to the signal at the tumor site. This case is well reproduced by ex-vivo samples of 90Y-marked Gastro-Entero-Pancreatic Neuroendocrine Tumors (GEP NET) in the bowel. These specimens indeed include at least three wide independent sources of background associated to three anatomical districts (mesentery, intestine, mucose). The study is based on the analysis of 37 lesions found on 5 samples belonging to 5 different patients. We show that the use of electrons, a short range particle, instead of γ particles, allows to limit counts read on a lesion to the sum of the tumor signal plus the background generated by the sole hosting district.The background on adjacent districts in the same specimen/patient is found to differ up to a factor 4, showing how the specificity and sensitivity of the ß--RGS technique can be fully exploited only upon a correct measurement of the contributing background. This locality has been used to set a site-specific cut-off algorithm to discriminate tumor and healthy tissue with a specificity of 100% and a sensitivity, on this test data sample, close to 100%. Factors influencing the sensitivity are also discussed. One of the specimens set allowed us evaluate the volume of the lesions, thus concluding that the probe was able to detect lesions as small as 0.04 mL in that particular case.

Peptide receptor therapies in neuroendocrine tumors.

Neuroendocrine tumors (NETs) are relatively rare tumors, mainly originating from the digestive system, able to produce bioactive amines and hormones. NETs tend to be slow growing and are often diagnosed when metastatic. The localization of a NETs and the assessment of the extent of disease are crucial for management. Commonly used diagnostic techniques include morphological imaging (ultrasound, computerized tomography, magnetic resonance), and functional imaging (somatostatin receptor scintigraphy, positron emission tomography techniques). Treatment is multidisciplinary and should be individualized according to the tumor type, burden, and symptoms. Therapeutic tools include surgery, interventional radiology, and medical treatments such as somatostatin analogues, interferon, chemotherapy, new targeted drugs and peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues. NETs usually over-express somatostatin receptors, thus enabling the therapeutic use of somatostatin analogues, one of the basic tools, able to reduce signs and symptoms of hormone hypersecretion, improve quality of life, and slow tumor growth. PRRT with somatostatin analogues 90Y-DOTATOC and 177Lu-DOTATATE has been explored in NETs for more than a decade. Present knowledge and clinical studies indicate that it is possible to deliver high-absorbed doses to tumors expressing sst2 receptors, with partial and complete objective responses in up to 30% of patients. Side effects, involving the kidney and the bone marrow, are mild if adequate renal protection is used. Moreover, a consistent survival benefit is reported. As NETs may also express cholecystokinin 2, bombesin, neuropeptide Y or vasoactive intestinal peptide receptors even simultaneously, the potential availability and biological stability of radio-analogues will improve the multireceptor targeting of NETs.

The ß- radio-guided surgery: Method to estimate the minimum injectable activity from ex-vivo test.

PURPOSE: Radio-guided surgery with ß- decays is a novel technique under investigation. One of the main advantages is its capability to detect small (⩽0.1 ml) samples after injecting the patient with low activity of radiopharmaceutical. This paper presents an experimental method to quantify this feature based on ex-vivo tests on specimens from meningioma patients. METHODS: Patients were enrolled on the basis of the standard uptake value (SUV) and the tumour-to-non-tumour activity ratio (TNR) resulted from 68Ga-DOTATOC PET exams. After injecting the patients with 93-167 MBq of 90Y-DOTATOC, 26 samples excised during surgery were analyzed with a ß- probe. The radioactivity expected on the neoplastic specimens was estimated according to the SUV found in the PET scan and the correlation with the measured counts was studied. The doses to surgeon and medical personnel were also evaluated. RESULTS: Even injecting as low as 1.4 MBq/kg of radiotracer, tumour residuals of 0.1 ml can be detected. A negligible dose to the medical personnel was confirmed. CONCLUSIONS: Radio-guided surgery with ß- decays is a feasible technique with a low radiation dose for both personnel and patient, in particular if the patient is injected with the minimum required activity. A correlation greater than 80% was observed between the measured counts and the expected activity for the lesion samples based on the individual SUV and the TNR. This makes identifiable the minimum injectable radiotracer activity for cases where 90Y is the utilized radionuclide.

Sentinel node biopsy after neoadjuvant treatment in breast cancer: Five-year follow-up of patients with clinically node-negative or node-positive disease before treatment.

PURPOSE: It is controversial whether sentinel node biopsy (SNB) without axillary dissection (AD) should be performed in cN1/2 breast cancer patients who become cN0 after neoadjuvant treatment, since the false negative rate (FNR) may be unacceptably high. We assessed outcomes to address this issue. METHODS: We retrospectively assessed 396 cT1-4, cN0/1/2 patients, who became or remained cN0 after neoadjuvant treatment and underwent SNB with at least one sentinel node (SN) found, and AD not performed if the SN was negative. RESULTS: After a median follow-up of 61 months (interquartile range 38-82), five-year overall survival was 90.7% (95% CI, 87.7-93.7) in the whole cohort, 93.3% (95% CI, 90.0-96.6) in those initially cN0, and 86.3% (95% CI, 80.6-92.1) in those initially cN1/2 (P = 0.12). Axillary failure occurred in only 1 (0.7%) initially cN1/2 patient who became cN0. In initially cN0 patients, and also initially cN1/2 patients who responded well to neoadjuvant treatment (ypT0/ypTx), SN-negativity was a significant predictor of good outcome, consistent with the known prognostic significance of axillary status, and suggesting that SN status accurately reflected axillary status. By contrast, in initially cN1/2 patients found to be ypT1/2/3, SN status (and whether or not AD was performed) had no influence on survival. CONCLUSIONS: These findings suggest that SNB is acceptable in cN1/2 patients who become cN0 after neoadjuvant therapy.

First ex vivo validation of a radioguided surgery technique with ß-radiation.

PURPOSE: A radio-guided surgery technique with ß(-)-emitting radio-tracers was suggested to overcome the effect of the large penetration of γ radiation. The feasibility studies in the case of brain tumors and abdominal neuro-endocrine tumors were based on simulations starting from PET images with several underlying assumptions. This paper reports, as proof-of-principle of this technique, an ex vivo test on a meningioma patient. This test allowed to validate the whole chain, from the evaluation of the SUV of the tumor, to the assumptions on the bio-distribution and the signal detection. METHODS: A patient affected by meningioma was administered 300MBq of (90)Y-DOTATOC. Several samples extracted from the meningioma and the nearby Dura Mater were analyzed with a ß(-) probe designed specifically for this radio-guided surgery technique. The observed signals were compared both with the evaluation from the histology and with the Monte Carlo simulation. RESULTS: we obtained a large signal on the bulk tumor (105cps) and a significant signal on residuals of ∼0.2ml (28cps). We also show that simulations predict correctly the observed yields and this allows us to estimate that the healthy tissues would return negligible signals (≈1cps). This test also demonstrated that the exposure of the medical staff is negligible and that among the biological wastes only urine has a significant activity. CONCLUSIONS: This proof-of-principle test on a patient assessed that the technique is feasible with negligible background to medical personnel and confirmed that the expectations obtained with Monte Carlo simulations starting from diagnostic PET images are correct.

Lymphoscintigraphy and radioguided biopsy of the sentinel axillary node in breast cancer.

UNLABELLED: Lymphoscintigraphy associated with radioguided biopsy of the sentinel node (SN) is well established in clinical practice for melanoma. In breast cancer, the SN concept is similarly valid, and lymphoscintigraphy is a useful method for localizing the axillary SN. The aim of this study was to optimize the lymphoscintigraphy technique in association with a gamma ray detecting probe (GDP) for identifying and removing the SN in breast cancer patients. METHODS: Two-hundred fifty patients with operable breast tumor underwent lymphoscintigraphy before surgery. Three different size ranges of 99mTc-labeled colloid particles (<50, <80 and 200-1000 nm) were used, with either subdermal (above tumor) or peritumoral injection. Early and late scintigraphic images were obtained in anterior and oblique projections, and the skin projection of the detected SN was marked. Sentinel nodes were identified and removed with the aid of the GDP during breast surgery; they were tagged separately. Complete axillary dissection followed. In 40 patients, a blue dye was also administered in addition to subdermal radiolabeled colloid to compare blue dye mapping with lymphoscintigraphy localization. RESULTS: Lymphoscintigraphy successfully revealed lymphatic drainage in 245 of 250 patients (98%). The axillary SN was identified in 240 patients (96%). SN biopsy correctly predicted axillary node status in 234 of 240 patients (97.5%). Lymphoscintigraphy and GDP detected the SN most easily and consistently when 200-1000 nm colloid was administered subdermally in an injection volume of 0.4 ml. Blue dye mapping was successful in 30 of 40 patients (75%). In 26 of these patients, the dye and lymphoscintigraphy identified the same node; in 4 cases different nodes were identified. None of these four patients had axillary disease. CONCLUSION: Lymphoscintigraphy is a simple procedure that is well tolerated by patients. Sentinel node identification is more reliable when large-size radiolabeled colloids are injected in a relatively small injection volume (0.4 ml). Use of a GDP greatly facilitates precise pinpointing and rapid removal of the SN.

Is there a role for sentinel node biopsy in early N0 tongue tumors?

BACKGROUND: Detecting metastases to the cervical lymph nodes is the main problem in the management of squamous cell carcinoma of the tongue. We investigated the ability of sentinel node (SN) biopsy to predict neck status in 11 patients with lateral T1-T2, N0, and M0 squamous cell carcinoma of the tongue who underwent ipsilateral neck dissection 30 to 40 days after primary surgery. METHODS: In 5 patients, technetium 99m-labeled particles were injected close to the operation scar on the day before neck dissection, and the labeled neck nodes were revealed by lymphoscintigraphy. The next 6 patients underwent lymphoscintigraphy both before surgery and before neck dissection. During neck dissection, the ipsilateral SNs were identified by using a hand-held probe and removed separately. RESULTS: Three patients (27%) had metastatic neck nodes. In all cases, labeled nodes were revealed by scintigraphy. Ipsilateral SNs were removed from 8 patients and correctly predicted the state of the neck (6 negatives and 2 positives). Lymphoscintigraphy before and after surgery revealed that drainage was modified after surgery in 5 of 6 patients; the pre-surgery drainage pattern varied markedly among the 5 pN0 patients. CONCLUSIONS: The technique allows easy and safe identification of SNs and shows promise in guiding selective neck dissection. Surgery on the primary tumor often modifies lymphatic drainage, so that SN biopsy may only be useful if the primary operation and neck dissection are performed at the same time.

Sentinel node localization in primary melanoma: learning curve and results.

Ninety primary melanoma patients were studied to investigate the importance of adopting the simultaneous use of patent blue dye (PBD) and lymphoscintigraphy plus gamma detection probe to locate the sentinel node (SN). In total 135 SNs in 105 basins were visualized preoperatively under a gamma camera after lymphoscintigraphy. When a SN was identified intraoperatively, its radioactivity level and colour were verified and documented. Two of the SNs seen on lymphoscintigraphy were not found. Using PBD 78.52% of the SNs were identified; 95.5% were identified using the gamma detection probe. Using both methods together 98.5% of the SNs were detected. Twenty-two patients (24.4%) had pathologically positive SNs. The surgical learning curve was assessed for the two techniques. The learning curve associated with the methodology was important in finding the SN when using PBD associated with lymphoscintigraphy, but not when the gamma detection probe was used; we found a statistically significant reduction in the percentage of stained SNs found using PBD in the initial 14 SNs biopsied compared with the subsequent 121 nodes. This is important as not all institutions have access to a gamma probe. The time required to identify each SN was documented and analysed. The duration of the procedure was significantly shorter for stained SNs than for non-stained SNs, which support the use of both PBD and the gamma probe. In conclusion, SN biopsy should be performed by surgeons and nuclear medicine doctors in co-operation, both methods being adopted simultaneously to reduce the percentage of procedure failures.

Pre-targeted locoregional radioimmunotherapy with 90Y-biotin in glioma patients: phase I study and preliminary therapeutic results.

The aim of this study was to determine the maximum-tolerated dose, of a pre-targeting three-step (3-S) method employing 90Y-biotin in the locoregional radioimmunotherapy (RIT) of recurrent high grade glioma, and to investigate the antitumor efficacy of this new treatment. Twenty-four patients with recurrent glioma underwent second surgical debulking and implantation of a catheter into the surgical resection cavity (SRC), in order to introduce the radioimmunotherapeutic agents [biotinylated monoclonal antibody (MoAb), avidin and 90Y-biotin]. Eight patients with anaplastic astrocytoma (AA) and 16 patients with glioblastoma (GBM) were injected with biotinylated anti-tenascin MoAb (2 mg), then with avidin (10 mg; 24 h later) and finally 90Y-biotin (18 h later). Each patient received two of these treatments 8-10 weeks apart. The injected activity ranged from 0.555 to 1.110 GBq (15-30 mCi). Dosage was escalated by 0.185 GBq (5 mCi) in four consecutive groups. The treatment was well tolerated without acute side effects up to 0.740 GBq (20 mCi). The maximum tolerated activity was 1.110 GBq (30 mCi) limited by neurological toxicity. None of the patients developed hematologic toxicity. In three patients infection occurred around the catheter. The average absorbed dose to the normal brain was minimal compared with that received at the SRC interface. At first control (after 2 months), partial (PR) and minor (MR) responses were observed in three GBM (1 PR; 2 MR) and three AA patients (1 PR; 2 MR) with an overall objective response rate of 25%. Stable disease (SD) was achieved in seven GBM and five AA patients (50%). There was disease progression in six GBM patients (25%), but in none of the AA patients. At the dosage of 0.7-0.9 GBq per cycle, locoregional 3-S-RIT was safe and produced an objective response in 25% of patients. Based on these encouraging results, phase II studies employing 3-S-RIT soon after first debulking are justified.

Regional cerebral metabolism of glucose in comatose and vegetative state patients.

Regional cerebral metabolism of glucose (rCMRglu) was evaluated in patients who were in a coma and vegetative state to determine the level of brain function during these conditions. rCMRglu was measured in 17 discrete brain regions with (/-) [18F] -fluoro-2-deoxy-D-glucose (FDG) and positrn emission tomography (PET) in 15 patients with ;brain pathology subsequent to cardiorespiratory arrest (CA), head trauma (HT), or brain ischemia (BI) resulting from cerebrovascular accident or brain surgery. Five comatose patients (Coma group, n = 5), and 10 vegetative state patients (VS, patients awake but not aware) were studied. The VA patients were subdivided, according to the length of their VS condition, into a VS group (n = 6, < 3 months if CA or BI patients, or < 12 months if HT patients) and a persistent vegetative state group (PVS, n = 4, > 3 months if CA or BI patients of > 12 months if HT patients.) Ten normal age-matched subjects served as control. Global CMRglu was 6.72 +/- 0.93 (+/-SD) mg/100 g/min in control subjects. It was significantly (p < - 0.001) reduced to 3.70 +/- 61 in coma, to 3.45 +/- in VS, and to 2.33 +/- 0.34 mg/100 g/min in PVS patients. rCMRglu was significantly reduced (p < - 01001) from control values in all the 17 structures surveyed in every patient. In the Coma and VS groups, there was an overlapping of rCMRglu in the majority of the brain structures. (ABSTRACT TRUNCATED AT 250 WORDS)

Long-term follow-up of 5262 breast cancer patients with negative sentinel node and no axillary dissection confirms low rate of axillary disease.

AIM: It is established that axillary dissection (AD) can be safely avoided in breast cancer patients with a negative sentinel node (SN). In the present study we assessed whether the rate of axillary disease was sufficiently low on long term follow-up to consolidate the policy of AD avoidance. METHODS: We retrospectively analysed data on 5262 consecutive primary breast cancer patients with clinically negative axilla and negative SN, treated from 1996 to 2006, who did not receive AD. We used univariate and multivariate analyses to assess the influence of patient and tumour characteristics on first events and survival. The primary endpoint was the development of axillary disease as first event. RESULTS: After a median follow-up of 7.0 years (interquartile range 5.4-8.9 years) survival for the series was high (91.3%; 95% CI 90.3-92.3 at 10 years) and only 91 (1.7%) patients developed axillary disease as first event. Axillary disease was significantly more frequent in patients with the following characteristics: <35 years at diagnosis, tumour >1 cm, multifocality/multicentricity, G3, ductal histotype, Ki67 ≥ 30%, peritumoral vascular invasion, luminal B-like subtype, HER2 positivity, mastectomy, and not receiving radiotherapy. CONCLUSION: Long-term follow-up of our large series confirms that axillary metastasis is infrequent when AD is omitted in SN-negative breast cancer patients, and has low impact on overall survival.

A novel radioguided surgery technique exploiting ß(-) decays.

The background induced by the high penetration power of the radiation is the main limiting factor of the current radio-guided surgery (RGS). To partially mitigate it, a RGS with ß(+)-emitting radio-tracers has been suggested in literature. Here we propose the use of ß(-)-emitting radio-tracers and ß(-) probes and discuss the advantage of this method with respect to the previously explored ones: the electron low penetration power allows for simple and versatile probes and could extend RGS to tumours for which background originating from nearby healthy tissue makes probes less effective. We developed a ß(-) probe prototype and studied its performances on phantoms. By means of a detailed simulation we have also extrapolated the results to estimate the performances in a realistic case of meningioma, pathology which is going to be our first in-vivo test case. A good sensitivity to residuals down to 0.1 ml can be reached within 1 s with an administered activity smaller than those for PET-scans thus making the radiation exposure to medical personnel negligible.