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M Cremonesi

Publications and source records attributed to M Cremonesi.

28 records · Page 2Linked to original sources

Radiation protection in radioguided surgery of breast cancer.

The protocols for sentinel lymph node biopsy and radioguided occult lesion localization could potentially be of great value in the management of breast cancer patients. Both involve the injection of a 99Tcm-labelled radiopharmaceutical close to or into the lesion, localization of the sentinel lymph node or occult lesion by scintigraphy, and surgical removal with the aid of a hand-held gamma-ray detector. We present dosimetric data on patients and hospital personnel involved in these procedures. For evaluation of radiation protection, we measured the absorbed dose and air kerma rate. Activity levels in excised tissues and surgical instruments were also determined. For patients, the mean absorbed dose to the abdomen was 0.45 mGy, which is low compared to doses received from other diagnostic examinations. For surgeons after 100 operations, the mean absorbed dose to the hands was 0.45 mGy and the mean effective dose 0.09 mSv. Absorbed doses to all hospital personnel involved in the procedures were very low compared to recommended annual limits stipulated by the International Commission on Radiological Protection. We conclude that these procedures, performed according to protocols laid down by the European Institute of Oncology, Milan, are safe from the point of view of radiological protection and that only routine precautions are necessary.

Breast Neoplasms↗

Combined treatment of advanced oropharyngeal cancer with external radiotherapy and three-step radioimmunotherapy.

The prognosis of patients with locally advanced head and neck cancer remains grim due to poor locoregional tumour control. In the attempt to eradicate residual disease, various novel modalities have been tested, among which radioimmunotherapy (RIT) has shown some potential. We present a case of locally advanced oropharyngeal carcinoma successfully treated with a combination of various treatments including surgery, radio-chemotherapy and three-step RIT, with the avidin-biotin pretargeting system. A partial tumour response was achieved after surgery and radio-chemotherapy; persistent disease was documented at computed tomography (CT), ultrasound (US) and immunoscintigraphy (ISG) 10 weeks after the end of chemo-radiotherapy. The good correlation between the tracer localization in the scintigraphic images and residual mass visualized at CT suggested the application of three-step RIT using systemic administration of yttrium-90 (py) biotin. At present, 17 months after RIT, the patient is alive with no evidence of disease as documented by magnetic resonance imaging (MRI) and US. This is the first case of complete clinical remission of a head and neck carcinoma induced by combined treatment including pretargeted RIT with 90Y-biotin.

Aged↗

Biochemical modifications of avidin improve pharmacokinetics and biodistribution, and reduce immunogenicity.

Pretargeting techniques using the avidin-biotin system have shown encouraging results in both diagnostic and therapeutic clinical trials. It has been shown that in cancer therapy the ideal agent to be used for pretargeting should have a plasma half-life longer than avidin and lower immunogenicity than streptavidin in order for these procedures to be applied safely and repeatedly in patients. We prepared a recombinant form of avidin with no carbohydrates and avidins, biochemically modified either by decreasing the positive charges with succinic anhydride or by linking polyethylene glycol (PEG) at three different molar ratios and evaluated their in vivo behaviour after i.p. administration in mice. The succinylation and PEGylation of avidin increased the plasma half-life proportionally to the degree of protein modification. The procedures, however, affected the biotin binding to some extent. The biodistribution studies showed that, for all six time points (ranging from 20 min to 18 h post-injection), the liver and kidney to blood ratios were lower for PEGylated avidins than native, recombinant and succinyl avidin. Recombinant and low PEGylated avidin evoked an immune response in all mice after at least three injections. Native, recombinant and succinyl avidins showed higher serum titres than PEGylated avidins. In conclusion, the conjugation of avidin to PEG chains (n = 7) originates a compound with a suitable blood clearance, low immunogenicity and concurrent low cross-reactivity with avidin.

Animals↗

[Radiation protection in the use of tracers in radioguided breast surgery].

PURPOSE: Recent techniques in nuclear medicine have permitted to implement new procedures useful in surgery. Among these, the procedures for locating sentinel lymph nodes and nonpalpable breast lesions are of great interest. The protocols for the location of the sentinel lymph node and for the radioguided location of occult lesions developed at the European Institute of Oncology (IEO, Milan) are based on the administration of radiopharmaceuticals labelled with Technetium-99m (99mTc). We evaluated the dosimetric data relative to patients and hospital personnel to assess whether specific radiation protection procedures are needed. MATERIAL AND METHODS: Fifty patients with nonpalpable breast lesions and 50 patients with suspected lymph node involvement were enrolled in this study. All the patients underwent surgery the day after in-loco administration of the radiopharmaceutical (11 MBq of 99mTc). The absorbed dose to the hospital personnel was estimated from the air kerma rate measured by ionization chamber at different distances from the patients at 0 and 16 hours after the radiopharmaceutical administration. In order to evaluate radiation protection for patients, absorbed doses were measured positioning thermoluminescent dosimeters on the patient's skin for about 16 hours. In the operating room, activity was measured on some excised tissues (lymph nodes and tumors) and on surgical instruments. RESULTS: Absorbed doses were very low for the clinical staff also in case of prolonged patient assistance. After 100 cases, the surgeon mean absorbed dose to the hands and mean effective dose were .45 mGy and .09 mGy, respectively. These values correspond to 1% of the annual dose limit to the hands and to 10% of the annual equivalent effective dose recommended for the population (ICRP 60 and law by decree 230/95). The absorbed dose to healthy tissues of the patients were lower than 1 mGy (mean values: contralateral breast: .9 mGy; abdomen .45 mGy). The mean activity detected in the excised tissues was 9 kBq and 900 kBq in the sentinel lymph nodes and in the tumor lesions (injection site), respectively. The activity detected on the surgical instruments, higher on gauzes (< 100 kBq), was negligible. CONCLUSIONS: From the radiation protection point of view, the data support the validity of our protocols. Absorbed doses to the hospital personnel are low and require neither a radiation protection control nor a classification of exposed workers as classes A or B. Special containers for radioactive wastes are necessary in the administration room but not in the operating room, where the levels of possible contamination are negligible.

Breast Neoplasms↗

Optimized sentinel node scintigraphy in breast cancer.

INTRODUCTION: Axillary lymph node dissection (ALND) represents an important staging procedure in the surgical treatment of breast cancer. However, it may result necessary in tumors of little dimensions because of low percentage of metastatic axillary lymph node (ALN). If a non invasive technique predicted the status of ALN, ALND procedures could be avoided. We carried out this study i) to establish the best technique to perform the lymphoscintigraphy for detecting the sentinel node in breast cancer and ii) to determine whether a clear sentinel node reliably predicts a disease free axilla. METHODS: 215 patients were submitted to the lymphoscintigraphy before surgery. Three different colloidal radiotracers with particle size ranging between < 50 and 1000 nm were injected sudermically or peritumorally. Early and late images were recorded in anterior and oblique projections and the SN was marked on the skin and biopsied using a gamma detection probe (GDP) during surgery. RESULTS: The SN was identified in 210/215 cases (97.6%). The SN accurately predicted axillary ALN status in 204/210 (97.1%) patients in whom a sentinel node was identified and in all the cases (45 patients) with tumor < 1.5 cm in diameter. In 38/101 cases with metastatic axillary nodes (37.7%) the only positive node was the SN. CONCLUSIONS: Lymphoscintigraphy can easily locate the SN in breast cancer. SN detection resulted easier when large size microcolloids were used. Subdermally administration appeared the best way of injection for palpable lesions. Breast cancer patients without clinical involvement of the axilla should undergo SN biopsy routinely and this may allow sparing complete axillary dissection when the SN is free of disease.

Antimony↗

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.

Antimony↗

Acquisition protocol for breast cancer imaging with technetium-99m-labeled synthetic peptide and technetium-99m-MDP.

UNLABELLED: Technetium-99m-MDP and, recently, a 99mTc-labeled synthetic decapentapeptide have been shown to localize in breast lesions. Our goal was to develop an acquisition protocol to improve image quality, to improve detection of axillary lymph nodes with disease and to compare the utility of the new radiotracer to 99mTc-MDP. METHODS: Ninety-three patients with documented breast carcinoma were studied. Thirty-eight patients were studied in the supine position with anterior and lateral views: eight patients were injected intravenously with 600-740 MBq 99mTc-EPPT and 30 patients with the same activity of 99mTc-MDP. A second group of 55 patients was studied using the same total activity: 20 patients were injected with 99mTc-EPPT and 35 patients with 99mTc-MDP. To improve results, patients were positioned standing up with their arm raised. The breast with a marker over the nipple touched the collimator in the oblique-lateral position. Early planar images (2-5 min postinjection) were acquired with this positioning for the healthy and the tumor breast, collecting 1500 K counts in a 256 x 256 matrix. Imaging of the axillary regions was performed while the patients were positioned supine and a frontal image was obtained at 10-15 min postinjection for 1800 K counts. RESULTS: This diagnostic study produced good quality images, with the breast lesions and axilla visualized. The positions had limitations due to the overlapping of other organs and to the proximity with the chest wall. CONCLUSION: Using this protocol, all primary lesions and 50% of the axillary lymph nodes with 99mTc-MDP, and 35% with 99mTc-EPPT, were detected as documented by histology. Our protocol may represent an improvement in the diagnosis and staging of breast cancer.

Axilla↗

Radioguided sentinel node biopsy to avoid axillary dissection in breast cancer.

BACKGROUND: Sentinel node (SN) biopsy may predict axillary status in breast cancer. We retrospectively analyzed more than 500 SN cases, to suggest more precise indications for the technique. METHODS: 99mTc-labeled colloid was injected close to the tumor; lymphoscintigraphy was then performed to reveal the SN. The next day, during surgery, the SN was removed by using a gamma probe. Complete axillary dissection followed, except in later cases recruited to a randomized trial. The SN was examined intraoperatively by conventional frozen section, in later cases by sampling the entire node and using immunocytochemistry. RESULTS: In the first series, the SN was identified in 98.7% of cases; in 6.7%, the SN was negative but other axillary nodes were positive; in 32.1%, the SN was negative by intraoperative frozen section but metastatic by definitive histology, prompting introduction of the exhaustive method. In the randomized trial, the SN was identified in all cases so far, the false-negative rate is approximately 6.5%, and in 15 cases, internal mammary chain nodes were biopsied. CONCLUSIONS: SN biopsy can reliably assess axillary status in selected patients. The problems are the SN detection rate, false negatives, and the intraoperative examination, which can miss 30% of SN metastases. Our exhaustive method overcomes the latter problem, but it is time consuming.

Axilla↗