Telehealth in oncofertility and breast cancer patients during COVID-19: preliminary results of insenoallasalute.it project.

OBJECTIVE: Breast cancer (BC) is the leading diagnosis in premenopausal patients. Lockdown measures during COVID-19 pandemic reduced facilities for premenopausal patients, impairing oncological and reproductive health. To reduce its effect, a telehealth program called insenoallasalute.it was designed in Italy. PATIENTS AND METHODS: A national-based multicentric observational study was undertaken by insenoallasalute.it study group (Italian Ministry of Health, Modena Hospital and Tor Vergata University Hospital) to raise awareness among women on a) BC and its negative role on reproductive health; b) increase adherence to screening programs and self-examination; c) present oncofertility strategies. A web-based platform with two sections was designed: an informative section and a telehealth application activated with a mobile one-time password. After a self-evaluation test to select premenopausal women with maternal desire and family or personal history for BC or ovarian cancer, and premenopausal women with maternity desires with prior medically assisted procreation, a dedicated agenda for telehealth evaluation was displayed and planned. In case the patients fulfilled the criteria for further evaluation, they were invited to perform an outpatient evaluation in one of the pilot centers. RESULTS: From July 2021 to December 2021, 2,830 single accounts were activated, and 2,450 (86.57%) completed the tests. 53 patients were selected to undergo telehealth consultation and 40 (80.0%) scheduled the telehealth visit. 6 patients underwent surgery in the study centers. CONCLUSIONS: In our experience insenoallasalute.it embodied an innovative solution to spread BC awareness, BC screening program, and oncofertility opportunities in the oncological population.

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.

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.

Impact of time to surgery after neoadjuvant chemotherapy in operable breast cancer patients.

BACKGROUND: The optimal time interval between the end of neoadjuvant systemic therapy (NST) and breast surgery is still unclear. It is not known if a delay in surgery might influence the benefit of primary chemotherapy. The aim of this study is to evaluate the relationship between time to surgery (TTS) and survival outcomes. PATIENTS AND METHODS: According to TTS, women with diagnosis of BC treated with NST were divided into two cohorts: group A = 21 days or fewer and group B = longer than 21 days. OS and RFS were estimated and compared according to TTS and known prognostic factors. RESULTS: A total of 319 patients were included in the study: 61 in group A and 258 in group B. Median TTS was 34 days. No association between clinical stage, nuclear grade, type of chemotherapy, type of surgery and TTS was detected. OS and RFS were significantly worse for group B compared with group A, with a hazard ratio of 3.1 (95% CI, 1.1-8.6 p = 0.03) and 3.1 (95% CI, 1.3-7.1 p = 0.008) respectively. Multivariate analysis confirmed that TTS was an independent prognostic factor in term of OS (p = 0.03) and RFS (p = 0.01). Even in the subgroup of patients with pCR, TTS continued to be an independent prognostic factor for both OS and RFS (p = 0.05 and p = 0.03). CONCLUSIONS: TTS after NST seems to influence survival outcomes. BC patients underwent surgery within 21 days experienced maximal benefit from previous treatment: this advantage is consistent and maintained over time.

[Hemolytic uremic syndrome in twin pregnancy at 32 weeks gestation with HELLP syndrome. Case report]. / Sindrome uremico emolitica in gravidanza gemellare alla 32(a) settimana con HELLp syndrome. Descrizione di un caso clinico.

Renal failure occurring in pregnancy or post partum is an unusual but well-described complication. Acute renal failure seems to be associated more often with HELLP syndrome rather than with pre-eclampsia or chronic hypertension. Probable overlapping of HELLP and hemolytic uremic syndrome in pregnancy or postpartum should be taken into consideration when treating pregnant women who show signs of proteinuria, hypertension, hematuria, increase of reticulocytes, decrease of haptoglobin with thrombocytopenia and microangiopathic hemolytic anemia. Our case refers to a 32 year old woman at 32 weeks gestation in twin pregnancy who presented with HELLP syndrome and renal failure. Immediately postpartum oliguria was noted and the laboratory analyses suggested the coexistence of HELLP and hemolytic uremic syndrome. In patients with gestosis and/or HELLP syndrome presenting oliguria combined with a decrease of hemoglobin level not due to intraoperative hematic leaks it is always necessary to ask for haptoglobin dosage. In treating hemolytic uremic syndrome it is very important to use a high dosage of plasma and sometimes plasmapheresis. HELLP syndrome contributes to various complications which are sometimes responsible for kidney or maternal mortality. In treating these patients early diagnosis combined with a specific treatment can considerably reduce kidney and maternal mortality.

Testing of microbial contamination during the preparation of the radiocompound [9°Y]DOTATOC for clinical trials: a process validation study by Media Fill approach.

AIM: Radioisotopes used in nuclear radiopharmacy possess short half-lives, not allowing enough time to wait for completion of sterility tests. Moreover, carrying out sterility tests on highly radioactive solutions inside the hospital microbiology laboratory arises concerns about radioprotection. Therefore, the release of radiopharmaceuticals for injection is allowed in microbial analysis. For this reason, the effectiveness of the aseptic procedures has to be continuously assessed in order to guarantee the safety of the drug. The aim of this study was to validate the sterile preparation of [9°Y]DOTATOC by means of media fill test. METHODS: In order to validate the process, a simulation test was used: the media fill test. To apply this method, operators simulated each step of the process using culture medium (Triptic Soy Broth, TSB) instead of actual radiopharmaceutical product. Media fill test procedure has been subdivided into 5 phases, from the simulation of reagent preparation through the dispensing operations up to ward delivery. After every step, the processed medium was incubated at 35 °C for 14 days. If the compounding procedures are adequately performed, no growth of microorganisms will be detected. RESULTS: Microbiological analyses, carried out on all vials obtained at the end of each step, showed no microbial growth. For this reason, sterility tests were considered satisfactory. CONCLUSION: Application of media-fill test allowed both to validate operative modality used for [9°Y]-DOTATOC handling and to attest the ability of operators who worked on it. Additionally, a correct quality control of the radiopharmaceutical i.v. preparations allows clinic infections control and prevention.

Improved radiotracing of oxytocin receptor-expressing tumours using the new [111In]-DOTA-Lys8-deamino-vasotocin analogue.

Oxytocin receptors (OTR) have been described in a number of tumours of different origin, and represent a new target for specific radiolabelled oxytocin (OT) analogues in cancer diagnosis and therapy. By linking the DOTA chelating agent to position 8 of the deamino derivative of Lys(8)-vasotocin (dLVT), we obtained a new compound (DOTA-dLVT) with the following characteristics: (1) it forms a monomeric and stable compound that binds to OTR with an affinity comparable to that of the endogenous OT ligand; (2) it is characterised by a very good selectivity profile for the human OTR, with a low affinity binding to the closely related V1a, V1b and V2 vasopressin receptor subtypes; (3) it induces rapid and persistent receptor internalisation and (4) when radiolabelled, [(111)In]-DOTA-dLVT is efficiently and selectively taken up by OTR-positive tumours grown in mice. These features makes radiolabelled DOTA-dLVT a very good candidate for the radiotargeting of OTR-expressing tumours.

90Y-DOTA-D-Phe1-Try3-octreotide in therapy of neuroendocrine malignancies.

Somatostatin receptors type 2 (sst(2)) are expressed in high concentration on numerous neudoendocrine tumors. The successful use of radiolabeled somatostatin analogs in imaging promoted further studies in utilizing them in radiopeptide therapy. The somatostatin analog [(90)Y-DOTA-D-Phe(1)-Try3]octreotide (DOTATOC) (DOTA: 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) possesses favorable characteristic for its therapeutic use; shows high affinity for sst(2), moderately high affinity for sst(5), and intermediate affinity for sst(3); high hydrophilicity; stable and facile labeling with (111) In and (90) Y. In this article we report our experience with (90)Y-DOTATOC in neuroendocrine tumors. Eighty-seven patients with neuroendocrine tumors were treated with a cumulated activity ranging from 7.4 to 20.2 GBq. Most patients responded with stabilization of disease (48%); however, objective responses were observed in 28% of patients (5% complete response). No major acute reactions were observed up to the activity of 5.55 GBq per cycle. The dose limiting was bone marrow toxicity and the maximal tolerated dose was defined as 5.18 GBq.