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Importance: Data about the optimal timing for the initiation of peptide receptor radionuclide therapy (PRRT) for advanced, well-differentiated enteropancreatic neuroendocrine tumors are lacking. Objective: To evaluate the association of upfront PRRT vs upfront chemotherapy or targeted therapy with progression-free survival (PFS) among patients with advanced enteropancreatic neuroendocrine tumors who experienced disease progression after treatment with somatostatin analogues (SSAs). Design, setting, and participants: This retrospective, multicenter cohort study analyzed the clinical records from 25 Italian oncology centers for patients aged 18 years or older who had unresectable, locally advanced or metastatic, well-differentiated, grades 1 to 3 enteropancreatic neuroendocrine tumors and received either PRRT or chemotherapy or targeted therapy after experiencing disease progression after treatment with SSAs between January 24, 2000, and July 1, 2020. Propensity score matching was done to minimize the selection bias. Exposures: Upfront PRRT or upfront chemotherapy or targeted therapy. Main outcomes and measures: The main outcome was the difference in PFS among patients who received upfront PRRT vs among those who received upfront chemotherapy or targeted therapy. A secondary outcome was the difference in overall survival between these groups. Hazard ratios (HRs) were fitted in a multivariable Cox proportional hazards regression model to adjust for relevant factors associated with PFS and were corrected for interaction with these factors. Results: Of 508 evaluated patients (mean ([SD] age, 55.7 [0.5] years; 278 [54.7%] were male), 329 (64.8%) received upfront PRRT and 179 (35.2%) received upfront chemotherapy or targeted therapy. The matched group included 222 patients (124 [55.9%] male; mean [SD] age, 56.1 [0.8] years), with 111 in each treatment group. Median PFS was longer in the PRRT group than in the chemotherapy or targeted therapy group in the unmatched (2.5 years [95% CI, 2.3-3.0 years] vs 0.7 years [95% CI, 0.5-1.0 years]; HR, 0.35 [95% CI, 0.28-0.44; P

AIM: Neuroendocrine tumors over-express somatostatin receptors and literature data have demonstrated the efficacy of the peptide receptor radionuclide therapy with somatostatin analogues labelled with high activities of b-emitting radioisotopes, such as (90)Y and (177)Lu. Yttrium-90 is a pure high energy b-emitter while (177)Lu is a b/g emitter of medium energy. We decided to evaluate an original tandem treatment based on administration of radiolabeled [DOTA(0),Tyr(3)]octreotate (DOTA-TATE) alternating (177)Lu and 90Y. Aim of this study was to evaluate the feasibility, the efficacy and the toxicity of this treatment in neuroendocrine tumors expressing somatostatin receptors relapsed or refractory to conventional therapies. METHODS: Patients were treated with four therapeutic cycles alternating [(177)Lu]DOTA-TATE (5.55 GBq) and [(90)Y]DOTA-TATE (2.6 GBq). Dosimetric evaluation after administration of [(177)Lu]DOTA-TATE allows to calculate the absorbed doses in healthy organs. Blood samples were collected at 5 min, 1, 6, 24, 48, 72, 96 h and scintigraphy was performed once a day for four days after administration. Toxicity was evaluated considering hematological parameters and renal toxicity was evaluated also by the glomerular filtration rate (GFR). Efficacy related with RECIST criteria. RESULTS: Up to now 26 patients entered the study and 16 patients completed all cycles. Treatment was well tolerated with no adverse event registered. No damage to healthy organs was revealed in accordance with the calculated absorbed doses. We had a partial response in 10/15 patients evaluated three months after the fourth treatment. CONCLUSIONS: Up to now only a few patients participated in and concluded this study; preliminary results are encouraging and indicate the feasibility of the study.

AIM: Since the second half of the 1980s, (131)I-MIBG has been widely used for treatment of patients with malignant pheochromocytoma. In 1991, at the International Meeting in Rome, it was agreed that (131)I-MIBG therapy induces significant tumor responses in about 30-50% of cases, long-term stabilization of disease in several cases and significant reduction of cathecolamine-related symptoms in almost all patients. Nevertheless, more than 20 years later, its therapeutic use in malignant phaeochromocytoma has not yet been standardized. Aim of the present study was to compare the use of low versus intermediate activity of MIBG to achieve better results in a shorter time with higher activities. METHODS: Two different modalities of (131)I-MIBG therapy were performed: before 2001, 12 patients (Group 1) received a fixed activity of 5.55 GBq/session. From 2001 to 2009, 16 patients (Group 2) were treated with 9.25-12.95 GBq/session. RESULTS: As expected, the overall response rate in Group 2 are slightly better. The most important result of increasing the single session activity was the shorter median time to achieve a significant response (7 versus 19 months), which was obtained with a lower median cumulative activity (11 versus 22 GBq) in a lower median number of sessions (2 versus 7). CONCLUSIONS: We demonstrated that intermediate single session activity shortened to one third the global treatment time, with similar efficacy and a moderate increment of toxicity. Consequently, the increase of (131)I-MIBG activity, without reaching myeloablative levels, can be recommended for standard treatment of pheochromocytoma and paraganglioma patients.

This paper analyzes the available data on the dosimetric approach and describes the use of dosimetry in the Division of Nuclear Medicine of the National Cancer Institute in Milan. Dosimetry is rarely performed when planning radio-iodine activity, although most of the available guidelines do mention this possibility, without giving any well defined indication. Aim of the present research was to validate the usefulness of dosimetry in the management of metastatic thyroid cancer. Benua (1962) set the limit of blood absorbed dose at 2 Gy to avoid hematological toxicity. Maxon (1983) determined at 80 Gy the dose to achieve complete destruction of a metastatic lesion. Dorn (2003) combined red marrow and lesion dosimetry showing that high activity administrations with less that 3 Gy to the red marrow are a safe and more effective with respect to fixed activities administrations. Lee (2008) reported 50% responses with high activity administrations based on blood dosimetry, in 47 patients which were unsuccessfully previously treated with fixed activities. Sgouros (2005) and Song (2006) introduced key parameters as Biological Effective Dose and Uniform Equivalent Dose in order to describe the effects of continuous low dose rate irradiation and non uniform activity uptake, typical of nuclear medicine treatments.Red marrow and lesion dosimetry (planar view) were performed during the treatment, without changing the fixed activity schema.This experience demonstrate first of all, that dosimetry is feasible in the clinical routine, and that it can provide the clinician with important information, no matter its often quoted limited numerical accuracy. A total of 17/20 lesion doses below 80 Gy have been detected. Three/17 (doses between 40 and 80 Gy) disappeared in the follow-up scintigram. Two/17 were undetectable at computed tomography or nuclear magnetic resonance. These data suggest that repetition of treatment on a lesion drastically reduces its uptake, with a loss of therapeutic efficacy along the sequence of fixed activity administrations.The usefulness of dosimetry should not be assessed only on the basis of patient survival or therapeutic efficacy; the possibility to avoid useless treatments should also be considered. According to the authors, individualized dosimetry could improve the management of metastatic differentiated thyroid cancer. Even post-therapeutic dosimetry, as performed at this institution, has a significant impact on clinical decision-making. The question for the future is how to include dosimetry into the patient management framework.

Iodine-131 metaiodobenzylguanidine (I-131 MIBG) has been used for the diagnosis and treatment of malignant pheochromocytomas (PHEO) and paragangliomas (PGL) since 1980's. Despite increasing amount of experience with iodine-131 (I-131) MIBG therapy, many important questions still exist. In this article, we will discuss the current problems learned from clinical experience in diagnosis and therapy of PHEO/PGL with I-131 MIBG, and present a sample case to emphasize the critical aspects for an optimal treatment strategy.

Skeletal metastases are one of the major clinical problems for the oncologist. Over the last several decades bone scintigraphy has been used extensively in detecting bone involvement since it can provide information about disease location, prognosis and the effectiveness of treatment. Bone scan offers the advantage of total body examination, and images bone lesions earlier than other techniques. In this paper the main clinical problems related to the most common applications of bone scan in breast, prostate, lung cancer and other tumours are discussed. The experience carried out at the National Cancer Institute of Milan by using bone SPECT to detect single bone metastases is reported. One hundred and eighteen patients with bone metastases (from different tumour types: breast, lung, prostate, lymphomas, etc.) were studied by planar scintigraphy, SPECT and other radiological modalities (CT, MRI or X-rays). The overall performances of bone SPECT were sensitivity: 90.5% (19/21), specificity 92.8% (90/97), positive predictive value 73% (19/26), negative predictive value 97.8% (90/92), accuracy 92.4% (109/118). Considering breast cancer, the most frequent pathology in our series, and the lumbar spinal tract, the most common skeletal segment involved, the figures of merit of SPECT were: sensitivity 100% (4/4), specificity 95.3% (41/43), positive predictive value 66.7% (4/6), negative predictive value 100% (41/41), accuracy 95.7% (45/47). In conclusion bone SPECT showed very good performances, in particular improving the predictive value of planar scan in the diagnosis of vertebral metastases.

The spine is the preferential site of metastases from several neoplasms. In the past years whole body bone scan (BS) with 99mTc-diphosphonates has been considered the first choice in detecting the skeletal involvement. However the presence of vertebral non-neoplastic pathology in oncologic patients can cause several false positive results and this increases the difficulty in defining the etiology of a focal uptake. Nowadays, technological development has provided new gamma cameras, which are able to perform tomographic acquisition (single photon emission tomography, SPET). This technique allows one to better define the anatomical location of the areas of increased uptake. In our study, 81 cancer patients, with suspected single skeletal metastases not defined by BS, were studied by SPET. The skeletal involvement was confirmed during at least 12 months follow up by means of clinical, radiological and nuclear medicine examinations. The overall malignant bone alterations were 14 while the benign ones were 67. The performances of SPET were: diagnostic sensitivity 92.8% (13/14), specificity 92.5% (62/67) positive predictive value 72.2% (13/18), negative predictive value 98.4% (62/63), accuracy 92.6% (75/81). Our conclusion is that bone SPET proved to be a very reliable tool in differentiating benign disease from metastatic involvement.

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 (

PURPOSE: We evaluated the oncologic efficacy of early inguinal lymph-node dissection, observation or dynamic sentinel node biopsy followed by delayed or selective inguinal lymph-node dissection in cN0 patients with penile squamous cell carcinoma. MATERIALS AND METHODS: Between 1980 and 2017 (inclusive), 296 evaluable consecutive cN0 penile squamous cell carcinoma patients underwent early inguinal lymph-node dissection (16), observation (114) or dynamic sentinel node biopsy (166). Median followup was 50 months. Tumor stage, grade, lympho-vascular invasion and age were considered. Kaplan-Meier plots illustrated 5-year inguinal relapse-free and cancer specific survival rates. Multivariable Cox regression models tested the treatment effect. Analyses were repeated after inverse probability of treatment weighting adjustment. RESULTS: The 5-year inguinal relapse-free survival and cancer specific survival rates following early, observation and dynamic sentinel node biopsy inguinal lymph-node dissection were 100%, 87%, 89%, and 84%, 81%, 85%, respectively. The 5-year crude inguinal relapse-free survival and cancer specific survival rates were 90% and 93% in low-risk patients undergoing observation. Clavien grade 3 complications were 0.6 vs 12.5% in the dynamic sentinel node biopsy and early inguinal lymph-node dissection group, respectively. After inverse probability after treatment weighting adjustment, 5-year inguinal relapse and cancer specific survival were 90% vs 73% and 90% vs 77% following dynamic sentinel node biopsy and observation, respectively. At multivariable Cox regression model, patients undergoing dynamic sentinel node biopsy had significantly lower inguinal relapse (HR 0.4, 95% CI 0.2-0.85, p 0.02) and cancer specific mortality (HR 0.29, 95% CI 0.11-0.77; p=0.01) compared to those under observation. The low number of patients undergoing early inguinal lymph-node dissection made a reliable comparison with this group impractical. CONCLUSIONS: Selective inguinal lymph-node dissection following dynamic sentinel node biopsy significantly improved inguinal relapse and cancer specific mortality when compared with observation, providing evidence of efficacy of dynamic sentinel node biopsy in clinical stage N0 squamous cell carcinoma of the penis.