Efficacy and safety of ramucirumab plus carboplatin and paclitaxel in untreated metastatic thymic carcinoma: RELEVENT phase II trial (NCT03921671).

BACKGROUND: Thymic carcinoma (TC) is a rare tumor with aggressive behavior. Chemotherapy with carboplatin plus paclitaxel represents the treatment of choice for advanced disease. Antiangiogenic drugs, including ramucirumab, have shown activity in previously treated patients. The RELEVENT trial was designed to evaluate the activity and safety of ramucirumab plus chemotherapy as first-line treatment in advanced TC. PATIENTS AND METHODS: This phase II trial was conducted within the Italian TYME network. Eligible patients had treatment-naïve advanced TC. They received ramucirumab, carboplatin and paclitaxel for six cycles, followed by ramucirumab maintenance until disease progression or intolerable toxicity. Primary endpoint was objective response rate (ORR) according to RECIST v1.1 as assessed by the investigator. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Centralized radiologic review was carried out. RESULTS: From November 2018 to June 2023, 52 patients were screened and 35 were enrolled. Median age was 60.8 years, 71.4% of patients were male and 85.7% had Masaoka-Koga stage IVB. The Eastern Cooperative Oncology Group performance status was 0 in 68.5% and 1 in 31.4% of patients. At the present analysis carried out some months after the interim analysis (earlier than expected) on 35 patients, ORR was 80.0% [95% confidence interval (CI) 63.1% to 91.6%]. At the centralized radiological review of 33/35 assessable patients, ORR was 57.6% (95% CI 39.2% to 74.5%). After a median follow-up of 31.6 months, median PFS was 18.1 months (95% CI 10.8-52.3 months) and median OS was 43.8 months (95% CI 31.9 months-not reached). Thirty-two out of 35 patients (91.4%) experienced at least one treatment-related adverse event (AE), of which 48.6% were AE ≥ grade 3. CONCLUSIONS: In previously untreated advanced TC, the addition of ramucirumab to carboplatin and paclitaxel showed the highest activity compared to historical controls, with a manageable safety profile. Despite the small number of patients, given the rarity of the disease, the trial results support the consideration of this combination as first-line treatment in TC.

Activity of osimeRTInib in non-small-cell lung Cancer with UNcommon epidermal growth factor receptor mutations: retrospective Observational multicenter study (ARTICUNO).

BACKGROUND: Osimertinib represents the standard of care for the treatment of advanced non-small-cell lung cancer (NSCLC) harboring classical epidermal growth factor receptor (EGFR) mutations, constituting 80%-90% of all EGFR alterations. In the remaining cases, an assorted group of uncommon alterations of EGFR (uEGFR) can be detected, which confer variable sensitivity to previous generations of EGFR inhibitors, overall with lower therapeutic activity. Data on osimertinib in this setting are limited and strongly warranted. PATIENTS AND METHODS: The ARTICUNO study retrospectively evaluated data on osimertinib activity from patients with advanced NSCLC harboring uEGFR treated in 21 clinical centers between August 2017 and March 2023. Data analysis was carried out with a descriptive aim. Investigators collected response data according to RECIST version 1.1 criteria. The median duration of response, progression-free survival (mPFS), and overall survival were estimated by the Kaplan-Meier method. RESULTS: Eighty-six patients harboring uEGFR and treated with osimertinib were identified. Patients with 'major' uEGFR, that is, G719X, L861X, and S768I mutations (n = 51), had an overall response rate (ORR) and mPFS of 50% and 9 months, respectively. Variable outcomes were registered in cases with rarer 'minor' mutations (n = 27), with ORR and mPFS of 31% and 4 months, respectively. Among seven patients with exon 20 insertions, ORR was 14%, while the best outcome was registered among patients with compound mutations including at least one classical EGFR mutation (n = 13). Thirty patients presented brain metastases (BMs) and intracranial ORR and mPFS were 58% and 9 months, respectively. Amplification of EGFR or MET, TP53 mutations, and EGFR E709K emerged after osimertinib failure in a dataset of 18 patients with available rebiopsy. CONCLUSION: The ARTICUNO study confirms the activity of osimertinib in patients with uEGFR, especially in those with compound uncommon-common mutations, or major uEGFR, even in the presence of BMs. Alterations at the E709 residue of EGFR are associated with resistance to osimertinib.

PEOPLE (NCT03447678), a first-line phase II pembrolizumab trial, in negative and low PD-L1 advanced NSCLC: clinical outcomes and association with circulating immune biomarkers.

BACKGROUND: The PEOPLE trial aimed to identify new immune biomarkers in negative and low programmed death-ligand 1 (PD-L1) (0%-49%) advanced non-small-cell lung cancer (aNSCLC) patients treated with first-line pembrolizumab. Here we report the main outcomes and the circulating immune biomarkers analysis. PATIENTS AND METHODS: The primary endpoint of this phase II trial was the identification of immune biomarkers associated with progression-free survival (PFS). Overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety were secondary endpoints. Absolute cell counts for 36 subsets belonging to innate and adaptive immunity were determined by multiparametric flow cytometry in peripheral blood at baseline and at first radiologic evaluation. An orthoblique principal components-based clustering approach and multivariable Cox regression model adjusted for clinical variables were used to analyze immune variables and their correlation with clinical endpoints. RESULTS: From May 2018 to October 2020, 65 patients were enrolled. After a median follow-up of 26.4 months, the median PFS was 2.9 months [95% confidence interval (CI) 1.8-5.6 months] and median OS was 12.1 months (95% CI 8.7-17.1 months). The ORR was 21.5%, DCR was 47.7% and median DoR was 14.5 months (95% CI 6.4-24.9 months). Drug-related grade 3-4 adverse events were 9.2%. Higher T cell and natural killer (NK) cell count at baseline and at the first radiologic evaluation were associated with improved PFS, DCR and OS. On the contrary, higher myeloid cell count at baseline or at the first radiologic evaluation was significantly associated with worse OS and DCR. CONCLUSIONS: Circulating immune biomarkers can contribute to predict outcomes in negative and low PD-L1 aNSCLC patients treated with first-line single-agent pembrolizumab.

Conversion factors for effective dose and organ doses with the air kerma area product in patients undergoing percutaneous transhepatic biliary drainage and trans arterial chemoembolization.

Conversion factors used to estimate effective (E) and organ doses (HT) from air Kerma area product (KAP) are required to estimate population doses in percutaneous transhepatic biliary drainage (PTBD) and trans arterial chemoembolization (TACE) interventional procedures. In this study, E and HT for ten critical organs/tissues, were derived in 64 PTBD and 48 TACE procedures and in 14,540 irradiation events from dosimetric, technical and geometrical information included in the radiation dose structured report using the PCXMC Monte Carlo model, and the ICRP 103 organ weighting factors. Conversion factors of: 0.13; 0.19; 0.26 and 0.32 mSv Gy-1 cm-2 were established for irradiation events characterized by a Cu filtration of 0.0; 0.1; 0.4 and 0.9 mm, respectively. While a single coefficient of conversion is not able to provide estimates of E with enough accuracy, a high agreement is obtained between E estimated through Monte Carlo methods and E estimated through E/KAP conversion factors accounting separately for the different modes of fluoroscopy and the fluorography component of the procedures. An algorithm for the estimation of effective and organ doses from KAP has been established in biliary procedures which considers the Cu filtration in the X-ray irradiation events. A similar algorithm could be easily extended to other interventional procedures and incorporated in radiation dose monitoring systems to provide dosimetric estimates automatically with enough accuracy to assess population doses.

Clinical outcomes to pemetrexed-based versus non-pemetrexed-based platinum doublets in patients with KRAS-mutant advanced non-squamous non-small cell lung cancer.

PURPOSE: KRAS mutation has been associated with enhanced dependency on the folate metabolism in preclinical studies. However, whether KRAS mutation correlates to increased sensitivity to pemetrexed in patients with advanced NSCLC is unknown. METHODS: Patients with advanced non-squamous NSCLC who had a documented EGFR and ALK WT genotype with simultaneous KRAS mutation assessment were evaluated for clinical outcome to pemetrexed- and non-pemetrexed-based first-line platinum doublet according to KRAS mutation status. RESULTS: Of 356 patients identified, 138 harbored a KRAS mutation. Among KRAS-mutant NSCLCs, those treated with platinum/pemetrexed (81/138) had significantly lower ORR (30.9% versus 47.4%, P = 0.05), DCR (51.8% versus 71.9%, P = 0.02) and shorter median progression-free survival [mPFS 4.1 versus 7.1 months, HR 1.48 (95% CI 1.03-2.12), P = 0.03] and median overall survival [mOS 9.7 versus 26.9 months, HR 1.93 (95% CI 1.27-2.94), P = 0.002] compared to those who received a non-pemetrexed-based platinum doublet (57/138). No difference in ORR, DCR, mPFS and mOS was observed between KRAS WT patients who received a pemetrexed-based (124/218) versus non-pemetrexed base platinum doublets (94/218). After adjusting for performance status, age and the presence of brain metastasis at baseline, treatment with pemetrexed-based platinum doublet was associated with an increased risk of death [HR 2.27 (95% CI 1.12-4.63), P = 0.02] among KRAS-mutant patients in multivariate analysis. CONCLUSION: Patients with KRAS-mutant lung adenocarcinoma have a poorer outcome on pemetrexed-based first-line chemotherapy. Whether KRAS-mutant NSCLCs should be excluded from pemetrexed-containing regimens should be assessed prospectively.

[Secondary labiaplasty: Retrospective study about 44 cases. Annual report SOFCPRE 2019]. / Nymphoplastie secondaire : étude rétrospective à propos de 44 cas. Rapport annuel de la SOFCPRE 2019.

INTRODUCTION: Labiaplasty is a surgery currently booming. The number of publications on this subject is also increasing significantly. With the increase of the operated cases, we see more and more consultations for revisions after a labiaplasty, called secondary labiaplasty. The author reports here his experience with secondary labiaplasties in 44 cases. MATERIAL AND METHOD: The study carried out by the author reports 44 cases divided into two categories of secondary labiaplasties. The first category is characterized by a wound dehiscence, including those following the author's lambda laser procedures, which are easily repaired under local anesthesia after border cutting and suture. The second category is characterized by over-resections or real amputations or even remains of atypical flaps. DISCUSSION: The over-resection is a technical fault. In this case, the technique used to improve the aesthetic, functional and psychological aspect is the use of the remains of labia minora in the form of a flap to avoid a dog-ear appearance at the anterior and posterior part. The use of lipofilling of the labia majora is to mask the area and improve the function. The future of this surgery is probably the reconstruction of the labia minora by local flaps. CONCLUSION: The conclusion of the study is that it is imperative that surgeons performing labiaplasties be trained in both anatomy and labiaplasty techniques and avoid as much as possible over-resections and amputations, mending being often difficult.

Evidence for swine and human papillomavirus in pig slurry in Italy.

AIMS: The diversity and the geographical distribution of swine papillomaviruses (PVs) are virtually unknown. The occurrence and the diversity of swine PV were therefore investigated in pig slurry collected in Italy, to contribute towards filling this gap in knowledge. METHODS AND RESULTS: Twenty-two slurry samples underwent analysis by nested PCR and DNA sequencing using published and newly designed specific primer pairs for Sus scrofa papillomavirus (SsPV) type 1 and 2 (SsPV1 and 2), along with degenerate PV-specific primers targeting the major coat protein L1 and the helicase protein E1. Overall, three samples (13·6%) were positive for SsPV1 by specific primers, and nucleotide (nt) sequences showed 99-100% nt identity with SsPV1 variant a (EF395818), while SsPV2 was not found in any sample. Using generic primers, eight samples (36·4%) were tested positive for human papillomavirus (HPV), and were characterized as follows: ß1-HPV8, ß1-HPV14, ß1-HPV206, ß2-HPV113, ß2-HPV120 and γ1-HPV173. Moreover, one unclassified γ-type was detected. CONCLUSIONS: Both swine and human PVs were detected in pig slurry in this study. The unexpected presence of HPV in pig waste could be explained as the result of an improper use of the sewage collection pits and/or with improper procedures of the operators. SIGNIFICANCE AND IMPACT OF THE STUDY: This study reports the first detection of SsPV1 in Italy, along with the first detection of HPVs in pig slurry samples in Italy, and expands our knowledge about PV diversity and geographic distribution.

Conversion factors of effective and equivalent organ doses with the air kerma area product in patients undergoing coronary angiography and percutaneous coronary interventions.

To derive effective dose (E), organ dose (HT) and conversion factors with the air kerma area product (KAP) in coronary angiography (CA) and percutaneous coronary intervention (PCI) by the radial route, using the ICRP 103 tissue weighting factors. The study included 34 patients referred for CA and 31 for PCI. E and HT were derived from in-the-field KAP measurements using Montecarlo methods. Median KAP of 23.2 and 56.8Gycm2 and E of 6.9 and 20.0mSv were found for CA and PCI, respectively. Mean KAP and E were significantly higher in males than in females (52.4±40.0 vs 32.3±16.6Gycm2; p=0.02) and (16.8±13.6 vs 10.7±5.8mSv; p=0.04). KAP (r=0.39; p=0.001) and E (r=0.34; p=0.005) showed a significant correlation with the patient's weight. Conversion factors between KAP and E (E/KAP) were 0.30±0.04mSvGy-1cm-2 for CA and 0.33±0.05mSvGy-1cm-2 for PCI. No significant differences in the E/KAP between males and females were found (0.31±0.05 vs 0.33±0.05; p=0.08). Again, no significant correlation was found between E/KAP and patient's weight (r=0.23; p=0.07). The correlation between E and KAP was excellent for CA (r=0.99) and PCI (r=0.96). The correlation between HT and KAP ranged from r=0.87 to r=1 and from r=0.71 to r=0.98 for CA and PCI, respectively. A single factor, the total KAP, could be used for a specific acquisition protocol to reliably estimate E and HT without the need of a patient's specific analysis. Conversion factors might be installation, X-ray beam quality or protocol dependent.

Human skin-derived fibroblasts used as a 'Trojan horse' for drug delivery.

BACKGROUND: Drug toxicity currently represents the main challenge of tumour chemotherapy. Our group recently developed a new method for drug delivery inspired by the 'Trojan Horse' concept. Human mesenchymal stem cells (hMSCs) have been shown to play the role of new 'horses' in delivering anti-tumour agents, without involving any genetic manipulation. As human stromal dermal fibroblasts (hSDFs) represent an interesting alternative to hMSCs, being easy to isolate, they could be an ideal candidate for this kind of procedure. AIM: To investigate whether hSDFs can take up and deliver paclitaxel (PTX) in sufficient concentrations to inhibit a very aggressive melanoma tumour (IgR39) in vitro. METHODS: hSDFs were primed with high doses of PTX, and then the effect of drug delivery on IgR39 melanoma proliferation in vitro was evaluated using several assays (antiproliferation, transwell cocultures, rosette assays and colony growth assays). Furthermore, the cell cycle and PTX uptake/release mechanism of hSDFs were studied both under both normal and hypoxic conditions. RESULTS: hSDFs incorporated PTX and then released it with unaffected pharmacological activity, inhibiting human IgR39 melanoma growth in vitro. The hypoxic conditions did not induce changes in cell cycle pattern and the uptake-release mechanism with PTX was not affected. CONCLUSIONS: hSDFs can be used as a Trojan horse, as the released drug was functionally active. These results indicated that these cells could be used for clinical treatment as the drug was released into the cellular environment and the primed cells underwent apoptosis.

Quality of life in patients treated by adjuvant radiotherapy for endometrial and cervical cancers: correlation with dose-volume parameters.

INTRODUCTION: Modern multidisciplinary cancer treatments aim at obtaining minimal influence on patients' quality of life (QoL). The purpose of this study was to assess QoL and correlate it with dose-volume parameters of organ at risks (OARs) in patients who received adjuvant radiotherapy for endometrial and cervical cancers. MATERIALS AND METHODS: We administered the EORTC QLQ-C30 and EN24 or CX24 questionnaires to 124 patients, 100 with endometrial cancer and 24 with cervical cancer treated with postoperative radiotherapy ± chemotherapy in regular follow-up. Bladder function, fecal incontinence or urgency and sexual functioning were investigated and correlated with dose-volume parameters of OAR by multiple linear regression analysis. This correlation was assessed by R (2) value. RESULTS: QoL was very high in the majority of patients (82.3 % of patients). Few patients referred urinary incontinence (3.2 %) or abdominal discomfort of high grade (4.0 %). We found a significant correlation between bladder V40, i.e., absolute percentage of bladder volume that received a dose of 40 Gy, and global health status (p < 0.05, R (2) = 0.17), urinary urgency (p < 0.05, R (2) = 0.24), urinary incontinence (p < 0.05, R (2) = 0.23) and dyspareunia (p < 0.05, R (2) = 0.04). We found also a correlation between global health status and mean dose to vagina (p < 0.05, R (2) = 0.17) and between maximum dose to lumbo-sacral plexus and abdominal pain (p < 0.05, R (2) = 0.07). CONCLUSIONS: Women treated with surgery and adjuvant radiotherapy for endometrial and cervical cancers have good QoL with minimal limitations of daily activities. QoL was correlated with dose-volume parameters such as bladder V40, mean dose to vagina, maximum dose to trigone and LSP.

An Adaptive Thresholding Method for BTV Estimation Incorporating PET Reconstruction Parameters: A Multicenter Study of the Robustness and the Reliability.

OBJECTIVE: The aim of this work was to assess robustness and reliability of an adaptive thresholding algorithm for the biological target volume estimation incorporating reconstruction parameters. METHOD: In a multicenter study, a phantom with spheres of different diameters (6.5-57.4 mm) was filled with (18)F-FDG at different target-to-background ratios (TBR: 2.5-70) and scanned for different acquisition periods (2-5 min). Image reconstruction algorithms were used varying number of iterations and postreconstruction transaxial smoothing. Optimal thresholds (TS) for volume estimation were determined as percentage of the maximum intensity in the cross section area of the spheres. Multiple regression techniques were used to identify relevant predictors of TS. RESULTS: The goodness of the model fit was high (R(2): 0.74-0.92). TBR was the most significant predictor of TS. For all scanners, except the Gemini scanners, FWHM was an independent predictor of TS. Significant differences were observed between scanners of different models, but not between different scanners of the same model. The shrinkage on cross validation was small and indicative of excellent reliability of model estimation. CONCLUSIONS: Incorporation of postreconstruction filtering FWHM in an adaptive thresholding algorithm for the BTV estimation allows obtaining a robust and reliable method to be applied to a variety of different scanners, without scanner-specific individual calibration.

Performance comparison of two resolution modeling PET reconstruction algorithms in terms of physical figures of merit used in quantitative imaging.

PURPOSE: Resolution modeling (RM) of PET systems has been introduced in iterative reconstruction algorithms for oncologic PET. The RM recovers the loss of resolution and reduces the associated partial volume effect. While these methods improved the observer performance, particularly in the detection of small and faint lesions, their impact on quantification accuracy still requires thorough investigation. The aim of this study was to characterize the performances of the RM algorithms under controlled conditions simulating a typical (18)F-FDG oncologic study, using an anthropomorphic phantom and selected physical figures of merit, used for image quantification. METHODS: Measurements were performed on Biograph HiREZ (B_HiREZ) and Discovery 710 (D_710) PET/CT scanners and reconstructions were performed using the standard iterative reconstructions and the RM algorithms associated to each scanner: TrueX and SharpIR, respectively. RESULTS: RM determined a significant improvement in contrast recovery for small targets (≤17 mm diameter) only for the D_710 scanner. The maximum standardized uptake value (SUVmax) increased when RM was applied using both scanners. The SUVmax of small targets was on average lower with the B_HiREZ than with the D_710. Sharp IR improved the accuracy of SUVmax determination, whilst TrueX showed an overestimation of SUVmax for sphere dimensions greater than 22 mm. The goodness of fit of adaptive threshold algorithms worsened significantly when RM algorithms were employed for both scanners. CONCLUSIONS: Differences in general quantitative performance were observed for the PET scanners analyzed. Segmentation of PET images using adaptive threshold algorithms should not be undertaken in conjunction with RM reconstructions.

Minimum acceptable sensitivity of intraoperative gamma probes used for sentinel lymph node detection in melanoma patients.

The aim of this study was to determine the suspension level for the sensitivity of an intraoperative scintillation gamma probe in the detection of the sentinel lymph node (SLN) in melanoma patients. Thirty-eight consecutive patients with melanoma were enrolled in the study during a 12-month period and underwent lymphatic scintigraphy after the peritumoral intradermal administration of about 14 MBq of (99m)Tc-nanocolloids. The SLNs were successfully removed during the surgical intervention about 4 h later. To identify and localize the SLN, a scintillation NaI(Tl) collimated probe was used. Predictably, the probe sensitivity decreased as the photopeak energy window was progressively narrowed, from 6.9 ± 0.7 counts per second (cps)/kBq (designated as the 'optimum,' or 'OPT,' sensitivity) to 2.5 ± 0.3 cps/kBq (LOW sensitivity) and to 1.4 ± 0.2 cps/kBq (VLOW sensitivity). Maximum lymph node count rates (cps) were determined for the foregoing energy windows prior to skin incision (PREOPT, PRELOW, PREVLOW, respectively) and in vivo after incision (INVOPT, INVLOW, INVVLOW). Forty-three SLNs were removed with a mean source-to-detector distance of 46 ± 24 mm (min 12 mm, max 92 mm). Four SLNs could not have been detected using PRELOW. This figure would have decreased to 34, with nine undetectable lymph nodes, with PREVLOW. One SLN could not have been identified using INVLOW and four could not have be identified using INVVLOW. In the clinical scenario of SLN detection in melanoma patients, a system sensitivity of 2.5 cps/kBq represents a suspension level, that is, a level under which the equipment must be suspended from clinical use and the poor performance must be investigated.

Permeability of gloves used in nuclear medicine departments to [(99m)Tc]-pertechnetate and [(18)F]-fluorodeoxyglucose: radiation protection considerations.

In order to evaluate the safety of the individual protection devices, the permeability of four different types of disposable gloves, commonly used in hospitals, was tested in relation to [(99m)Tc]-pertechnetate and to [(18)F]-fluorodeoxyglucose ([(18)F]-FDG). From these radiopharmaceutical solutions, a drop was deposited on the external surface of the glove which was opened and stretched with the external surface placed upward. The smear test technique permitted to evaluate the activity onto the inner surface of the glove at different times. The smear tests were measured in a well sodium iodide detector calibrated in efficiency for (99m)Tc and (18)F. The permeability was tested on ten samples of each type of gloves and was expressed as the ratio of the activity onto the inner surface at each time interval to the activity deposited on the external surface of the glove. For each type of gloves and for each sampling time, mean value, standard deviation and percentage coefficient of variation of permeability were evaluated. One type of gloves showed a low resistance to permeation of both radiopharmaceuticals, while another one only to pertechnetate. The other gloves were good performers. The results of this study suggest to test permeability for gloves used for handling radiopharmaceuticals, before their adoption in the clinical routine. This practice will provide a more careful service of radiation protection for nuclear medicine department staff.

Dysphagia after definitive radiotherapy for head and neck cancer. Correlation of dose-volume parameters of the pharyngeal constrictor muscles.

BACKGROUND: Dysphagia is a complication of head and neck cancer patients undergoing radiotherapy (RT). We analysed frequency and severity of swallowing dysfunction and correlated these findings with dose-volume histograms (DVHs) of the pharyngeal constrictor muscles. METHODS: A total of 50 patients treated by radical RT were enrolled. DVHs of constrictor muscles were correlated with acute and late dysphagia and with the items of three quality of life questionnaires. RESULTS: Mean dose to superior and middle constrictor muscles (SCM, MCM), partial volume of SCM and MCM receiving a dose ≥ 50 Gy dose to the whole constrictor muscles ≥ 60 Gy and tumour location were associated to late dysphagia at univariate analysis. Mean dose to the MCM was the only statistically significant predictor of late dysphagia at the multivariable analysis. CONCLUSION: The study shows a significant relationship between long-term dysphagia and mean doses to SCM, MCM, whole constrictor muscles, and oropharyngeal tumour. This finding suggests a potential advantage in reducing the RT dose to swallowing structures to avoid severe dysphagia.

Perfusion computed tomography assessments of peri-enhancing brain tissue in high-grade gliomas.

PURPOSE: This study was undertaken to identify tumoural infiltration of peri-enhancing brain tissue in patients with glioblastoma by means of perfusion computed tomography (PCT) parameters, cerebral blood volume (CBV) and permeability surface (PS). MATERIALS AND METHODS: Eight patients with surgically treated glioblastoma who were eligible for radiotherapy and nine patients with brain metastases from lung and breast cancer underwent CT before and after injection of contrast medium. CBV and PS were calculated in the contrast-enhancing lesion area, in the area of perilesional oedema and in the normal-appearing white matter (NAWM), normalised to contralateral symmetrical areas. RESULTS: No significant differences were found for normalised CBV (nCBV) and nPS in NAWM regions between metastasis and glioma. Significant differences in nPS (p<0.005) were found between the typically vasogenic oedema surrounding the metastases and signal alteration surrounding the glial neoplasm. On the contrary, no significant differences were detected in the same areas for nCBV. CONCLUSIONS: PCT can analyse the histopathological substrate underlying the hypodense peritumoural halo and differentiate between vasogenic oedema and neoplastic infiltration on the basis of the PS parameter. In our study, PS was more informative than CBV. These findings can be used to integrate plans for radiation therapy and/or surgery.

Diagnostic accuracy and agreement between whole-body diffusion MRI and bone scintigraphy in detecting bone metastases.

PURPOSE: This study was done to determine the diagnostic value of whole-body magnetic resonance using diffusion-weighted imaging with background suppression (WB-DWIBS) for detecting bone metastases compared with whole-body bone scintigraphy (WB-BS). MATERIALS AND METHODS: Twenty-three patients with solid tumours underwent both WB-DWIBS imaging and WBBS. A nuclear medicine specialist interpreted WB-BS images and two blinded radiologists, first independently and then jointly, interpreted the WB-DWIBS images by completing a reading grid categorising the skeletal segments. Cohen's k statistic was used to determine interobserver agreement in reading the WB-DWIBS images and the agreement between WB-BS and WB-DWIBS. Sensitivity and specificity were calculated per patient and per lesion. RESULTS: Interobserver agreement in reading the WBDWIBS images was substantial or good, with κ=0.68. Analysis of agreement between the nuclear physician's and the radiologists' readings provided κ=0.87 [95% confidence interval (CI)=0.76-0.98)] Per-lesion analysis gave a sensitivity of 80% (95% CI=75-85) and a specificity of 98.2% (95% CI=96.5-99.8). CONCLUSIONS: We found a good level of interobserver agreement for the WB-DWIBS images and an excellent level of agreement in the subjective judgement of presence or absence of disease between WB-BS and WB-DWIBS after consensual double reading. WB-DWIBS has the same specificity as WB-BS in detecting bone metastases. The anatomical sites exhibiting the highest level of disagreement between WB-DWIBS and WB-BS are the pelvis, the coccyx, and the sternum, all sites at which detection with WB-BS has the greatest limitations.

[Metabolomic profiles of exhaled breath condensate of 39 nickel exposed workers]. / Profili metabolomici del condensato espiratorio di 39 lavoratori esposti a nichel.

Nickel compounds have proven lung carcinogenic effects and their processing involve a large amount of population. The aim of this study was to investigate the metabolomic profiles of Exhaled Breath Condensate (EBC) of a group of nickel exposed workers. Nickel in blood, urine and EBC of 39 workers (electroplaters) and 50 controls was measured. The 10 most nickel exposed workers were chosen for the analysis of EBC metabolomic profiles, matched to controls by gender and smoke habits. All the samples were analyzed using the HPLC-MS/MS system (High-Performance Liquid Chromatography/Mass Spectrometry). The profiles of the spectra obtained by the mass spectrometer (Orbitrap) analysis were processed using the MZmine 2.4 software. Nickel concentrations in EBC of the exposed workers were significantly higher compared to controls (1.39 microg/L; 0.039 microg/L, p = 0.017). The observation of the metabolomic profiles pointed out a significantly different response pattern between the exposed and the controls. This result was further studied by a subsequent processing with the XCMS program: an overexpression of 3 hypothetical substances in controls compared to exposed was detected. Although these data must be considered as preliminary, it has been observed that the mass-to-charge ratio of one of these substances may respond to the Phenylacethylglutamine (PAG) one, whose role in the control of cellular cycle is controversial and uncertain. Even if further studies to confirm these results are necessary, the analysis of the metabolomic profiles in the biological matrices is supposed to provide useful information both in the clinical and in the prevention fields.

Characterization of the [(153)Sm]Sm-EDTMP pharmacokinetics and estimation of radiation absorbed dose on an individual basis.

[(153)Sm]Sm-EDTMP is a radiopharmaceutical used in palliation cares of bone metastases. The purpose of this study is to provide an explicit description of [(153)Sm]Sm-EDTMP pharmacokinetics, adopting a simple three-compartmental model with the analytical expressions calculating the rate constants and determining biodistribution parameters, like radiopharmaceutical uptake and clearance. This biokinetic model allowed us to calculate on an individual basis the dose to bone surface and to red bone marrow and to assess the degree of variability in dosimetric parameters using a fixed administered activity based only on patient weight. In this study twenty patients were enrolled and were treated with [(153)Sm]Sm-EDTMP, administering a fixed activity per kilogram (37 MBq/kg); blood and urine samples were collected during 24 h post treatment. The median value of the administered activity was 2.7 GBq. Blood clearance confirmed that an aliquot of [(153)Sm]Sm-EDTMP rapidly localizes and is retained in bone, while the remainder is rapidly cleared from the blood pool by the urinary system. Our data show a bi-exponential clearance from blood: the rapid component has a half life median value of 6 min (range: 2-24 min), while the slow one has a half life median value of 1.4 h (range: 0.6-5.8 h). Median value of the urinary excretion is 40 (range: 3-75) % of the administered activity. Our model shows the behaviour of a tracer which is distributed in the extracellular space of the body, localized in the skeleton and excreted via glomerular filtration. Half life median values of [(153)Sm]Sm-EDTMP transferring between compartments, T(1/2) (blood→ECF), T(1/2) (ECF→blood) are 7.4 (range: 1.9-37) and 48 (range: 8-408) min, respectively. Median values of half lives of [(153)Sm]Sm-EDTMP clearance through the urine and of uptake into bone are 1.0 (range: 0.1-6.0) and 1.6 (range: 0.6-9.0) h, respectively. Median value of red marrow absorbed dose is 2.1 (range: 0.7-3.5) Gy and 0.8 (range: 0.3-2.1) Gy/GBq, while median value of bone surface absorbed dose is 11.5 Gy (range: 5.0-18.4) and 4.4 (range: 2.3-14.3) Gy/GBq. It is remarkable that there is a really great biological variability within patients, especially considering the excreted activity. The cumulated activity in bone and red marrow doses were significantly higher in prostate cancer, where metastatic bone lesions are osteoblastic, than in breast cancer where metastatic bone lesions are osteolytic or mixed (lytic/blastic). The relevant biological variability in biodistribution and metabolism of [(153)Sm]Sm-EDTMP suggests that the fixed administered activity based on patient weight is not sufficient to optimize the treatment and a better optimization would be reached by using a predictive dosimetry tailored to individual patient characteristics.

Threshold segmentation for PET target volume delineation in radiation treatment planning: the role of target-to-background ratio and target size.

A multivariable approach was adopted to study the dependence of the percentage threshold [TH(%)] used to define the boundaries of 18F-FDG positive tissue on emission scan duration (ESD) and activity at the start of acquisition (Aacq) for different target sizes and target-to-background (T/B) ratios. An anthropomorphic model, at least for counting rate characteristics, was used to study this dependence in conditions resembling the ones that can be encountered in the clinical studies. An annular ring of water bags of 3 cm thickness was fitted over an International Electro-technical Commission (IEC) phantom in order to obtain counting rates similar to those found in average patients. The scatter fraction of the modified IEC phantom was similar to the mean scatter fraction measured on patients, with a similar scanner. A supplemental set of microhollow spheres was positioned inside the phantom. The NEMA NU 2-2001 scatter phantom was positioned at the end of the IEC phantom to approximate the clinical situation of having activity that extends beyond the scanner field of view. The phantoms were filled with a solution of water and 18F (12 kBq/mL) and the spheres with various T/B ratios of 22.5, 10.3, and 3.6. Sequential imaging was performed to acquire PET images with varying background activity concentrations of about 12, 9, 6.4, 5.3, and 3.1 kBq/mL. The ESD was set to 60, 120, 180, and 240 s/bed. Data were fitted using two distinct multiple linear regression models for sphere ID < or = 10 mm and sphere ID > 10 mm. The fittings of both models were good with an R2 of 0.86 in both cases. Neither ESD nor Aacq resulted as significant predictors of the TH(%). For sphere ID < or =10 mm the target size was the most significant predictor of the TH(%), followed by the T/B ratio, while for sphere ID > 10 mm the explanatory power of the target size and T/B ratio were reversed, the T/B ratio being now the most important predictor of the TH(%). Both the target size and T/B ratio play a major role in explaining the variance of the TH(%), throughout the whole range of target sizes and T/B ratios examined. Thus, algorithms aimed at automatic threshold segmentation should incorporate both variables with a relative weight which critically depends on target size.