Association of quantitative MRI-based radiomic features with prognostic factors and recurrence rate in oropharyngeal squamous cell carcinoma.

Radiomics focuses on extracting a large number of quantitative imaging features and testing both their correlation with clinical characteristics and their prognostic and predictive values. We propose a radiomic approach using magnetic resonance imaging (MRI) to decode the tumor phenotype and local recurrence in oropharyngeal squamous cell carcinoma (OPSCC). The contrast-enhanced T1-weighted sequences from baseline MRI examinations of OPSCC patients treated between 2008 and 2016 were retrospectively selected. Radiomic features were extracted using the IBEX software, and hiegrarchical clustering was applied to reduce features redundancy. The association of each radiomic feature with tumor grading and stage, HPV status, loco-regional recurrence within 2 years, considered as main endpoints, was assessed by univariate analysis and then corrected for multiple testing. Statistical analysis was performed with SAS/STAT® software. Thirty-two eligible cases were identified. For each patient, 1286 radiomic features were extracted, subsequently grouped into 16 clusters. Higher grading (G3 vs. G1/G2) was associated with lower values of GOH/65Percentile and GOH/85Percentile features (p=0.04 and 0.01, respectively). Positive HPV status was associated with higher values of GOH/10Percentile (p=0.03) and lower values of GOH/90Percentile (p=0.03). Loco-regional recurrence within 2 years was associated with higher values of GLCM3/4-7Correlation (p=0.04) and lower values of GLCM3/2-1InformationMeasureCorr1 (p=0.04). Results lost the statistical significance after correction for multiple testing. T stage was significantly correlated with 9 features, 4 of which (GLCM25/180-4InformationMeasureCorr2, Shape/MeanBreadth, GLCM25/90-1InverseDiffMomentNorm, and GLCM3/6-1InformationMeasureCorr1) retained statistical significance after False Discovery Rate correction. MRI-based radiomics is a feasible and promising approach for the prediction of tumor phenotype and local recurrence in OPSCC. Some radiomic features seem to be correlated with tumor characteristics and oncologic outcome however, larger collaborative studies are warranted in order to increase the statistical power and to obtain robust and validated results.

Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer.

BACKGROUND: Ipsilateral breast cancer recurrence (IBTR) occurs in about 7% of patients with primary invasive breast tumor. Salvage mastectomy and breast reconstruction are often discussed and latissimus dorsi (LD) flap is frequently proposed. METHODS: We retrospectively investigated 111 consecutive locally relapsing patients who underwent salvage mastectomy and immediate LD reconstruction. All included patients with IBTR previously underwent conserving surgery for BC, and received a postoperative irradiation. Primary endpoints were disease free survival and overall survival. Secondary endpoints were surgical complications and re-interventions. RESULTS: Invasive ductal cancer was the most frequent histotype (60.4%) of breast cancer reappearance. rpT1, rpT2 and rpT3 were observed respectively in 50.5%, 20,7% and 3,6% of the patients. rpTis occurred in 11,7% of cases. Positive axillary nodes were observed in 9,9% of patients at reappearance. Post-operative complication other than seroma occurred in 17,1% of patients, while seroma at the donor site was observed in 61.3% of cases. At 5-year after surgery overall survival was 92% (95% CI: 85%-96%) and disease free survival was 78% (95% CI: 69%-85%). CONCLUSIONS: Immediate latissimus dorsi flap reconstruction in selected patients with isolated breast tumor recurrence, which occurred after breast irradiation, provides an effective treatment with a satisfactory outcome.

Single Hepatocellular Carcinoma approached by curative-intent treatment: A propensity score analysis comparing radiofrequency ablation and liver resection.

INTRODUCTION: Patients with a single small Hepatocellular Carcinoma (HCC) may be definitively treated by Radiofrequency ablation (RFA) with a very low rate of peri-operative morbidity. However, results are still controversial comparing RFA to Liver Resection (LR). METHODS: All consecutive patients treated by RFA or LR for a single untreated small HCC on liver cirrhosis between January 2006-December 2016 were enrolled. Patients were matched 1:1 basing on: age, MELD-score, platelet count, nodule's diameter, HCV status, α-fetoprotein level, and Albumin-Bilirubin score. First analysis compered LR to RFA. Second analysis compared Laparoscopic LR (LLR) to RFA. RESULTS: Of 484 patients with single small HCC, 91 patients were selected for each group after a 1:1 propensity score matching (PS-M). The 5-years OS was 70% and 60% respectively for LR and RFA group (P = 0.666). The 5-year RFS was 36% and 21% respectively for LR and RFA group (P < 0.001). Patients treated by LR had a significantly longer hospital stay and higher complications rate. Comparing 50 cases of LLR and 50 of RFA, the 5-years OS was 79% and 56% respectively for LLR and RFA group (P = 0.22). The 5-year RFS was 54% and 19% respectively for LR and RFA group (P < 0.001). Post-operative complications were not significantly different. CONCLUSIONS: LLR confers similar peri-operative complications rate compared to RFA. LLR should be considered as a first-line approach for the treatment of a single small HCC as it combines the effectiveness of open LR and the safety profile of RFA.

Lower Body vs. Upper Body Resistance Training and Arterial Stiffness in Young Men.

Resistance training has been shown to increase arterial stiffness. The purpose of the present study was to examine and compare the systemic arterial stiffness responses to acute lower body (LRT) and upper body (URT) resistance training. 20 healthy young men [median age: 26 years (interquartile range 23, 32)] underwent LRT, URT and whole body resistance training (WRT). Before and immediately after, as well as 20, 40 and 60 min after each training session, we measured the cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV) using VaSera VS-1500 N. We used mixed models for repeated measurements to estimate the post-exercise differences in CAVI and baPWV between the 3 resistance training modes. Immediately after exercise cessation, both CAVI and baPWV were lower for LRT compared with URT [CAVI: - 0.93 (95% confidence interval [CI] - 1.15, - 0.70); baPWV: - 2.08 m/s (95% CI - 2.48, - 1.67)]. Differences between LRT and URT gradually decreased during follow-up. Compared with WRT, LRT induced a decrease and URT an increase in arterial stiffness across all time points. In conclusion, LRT presents more favorable post-exercise arterial stiffness than URT. Our results suggest that LRT or WRT may be preferred over URT in individuals with impaired arterial stiffness.

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.

Use of the FLUKA Monte Carlo code for 3D patient-specific dosimetry on PET-CT and SPECT-CT images.

Patient-specific absorbed dose calculation for nuclear medicine therapy is a topic of increasing interest. 3D dosimetry at the voxel level is one of the major improvements for the development of more accurate calculation techniques, as compared to the standard dosimetry at the organ level. This study aims to use the FLUKA Monte Carlo code to perform patient-specific 3D dosimetry through direct Monte Carlo simulation on PET-CT and SPECT-CT images. To this aim, dedicated routines were developed in the FLUKA environment. Two sets of simulations were performed on model and phantom images. Firstly, the correct handling of PET and SPECT images was tested under the assumption of homogeneous water medium by comparing FLUKA results with those obtained with the voxel kernel convolution method and with other Monte Carlo-based tools developed to the same purpose (the EGS-based 3D-RD software and the MCNP5-based MCID). Afterwards, the correct integration of the PET/SPECT and CT information was tested, performing direct simulations on PET/CT images for both homogeneous (water) and non-homogeneous (water with air, lung and bone inserts) phantoms. Comparison was performed with the other Monte Carlo tools performing direct simulation as well. The absorbed dose maps were compared at the voxel level. In the case of homogeneous water, by simulating 10(8) primary particles a 2% average difference with respect to the kernel convolution method was achieved; such difference was lower than the statistical uncertainty affecting the FLUKA results. The agreement with the other tools was within 3­4%, partially ascribable to the differences among the simulation algorithms. Including the CT-based density map, the average difference was always within 4% irrespective of the medium (water, air, bone), except for a maximum 6% value when comparing FLUKA and 3D-RD in air. The results confirmed that the routines were properly developed, opening the way for the use of FLUKA for patient-specific, image-based dosimetry in nuclear medicine.

Kidney dosimetry in ¹77Lu and 9°Y peptide receptor radionuclide therapy: influence of image timing, time-activity integration method, and risk factors.

Kidney dosimetry in (177)Lu and (90)Y PRRT requires 3 to 6 whole-body/SPECT scans to extrapolate the peptide kinetics, and it is considered time and resource consuming. We investigated the most adequate timing for imaging and time-activity interpolating curve, as well as the performance of a simplified dosimetry, by means of just 1-2 scans. Finally the influence of risk factors and of the peptide (DOTATOC versus DOTATATE) is considered. 28 patients treated at first cycle with (177)Lu DOTATATE and 30 with (177)Lu DOTATOC underwent SPECT scans at 2 and 6 hours, 1, 2, and 3 days after the radiopharmaceutical injection. Dose was calculated with our simplified method, as well as the ones most used in the clinic, that is, trapezoids, monoexponential, and biexponential functions. The same was done skipping the 6 h and the 3 d points. We found that data should be collected until 100 h for (177)Lu therapy and 70 h for (90)Y therapy, otherwise the dose calculation is strongly influenced by the curve interpolating the data and should be carefully chosen. Risk factors (hypertension, diabetes) cause a rather statistically significant 20% increase in dose (t-test, P < 0.10), with DOTATATE affecting an increase of 25% compared to DOTATOC (t-test, P < 0.05).

Molecular characterization of EGFR and EGFR-downstream pathways in triple negative breast carcinomas with basal like features.

AIMS: Triple negative breast cancer with basal like features (TN-BCBL) do not benefit from hormonal and anti-HER2 therapies. As a considerable fraction of TN-BCBLs shows EGFR deregulation, EGFR-targeted therapies have been proposed as an option. The characterization of EGFR and EGFR-downstream members may therefore provide important predictive information. METHODS AND RESULTS: Based on morphological and immunophenotypic features, we identified 38 TN-BCBLs that were subsequently investigated for alterations in EGFR signaling pathways. EGFR and PTEN protein levels were studied by immunohistochemistry, EGFR gene status by FISH, EGFR, H-Ras, K-Ras, N-Ras, BRAF and PIK3CA gene mutations by direct sequencing. EGFR overexpression and loss of PTEN expression characterized the majority of TN-BCBLs (76% and 74% of patients, respectively). EGFR gene copy number gain (FISH+) was identified in 51% of analyzable patients. PIK3CA gene mutations were detected in three cases (8%), whereas EGFR, H-Ras, K-Ras, N-Ras and BRAF genes showed no mutations. Overall, out of 17 patients classified as FISH+, 12 cases (70%) showed a concomitant alteration in PI3K/PTEN pathway. CONCLUSIONS: These results provide evidence that the efficacy of anti-EGFR drugs in TN-BCBL patients could be impaired by frequent alterations in the PI3K/PTEN axis, and suggest that TN-BCBLs could benefit from tailored treatments against this axis.

A free database of radionuclide voxel S values for the dosimetry of nonuniform activity distributions.

The increasing availability of SPECT/CT devices with advanced technology offers the opportunity for the accurate assessment of the radiation dose to the biological target volume during radionuclide therapy. Voxel dosimetry can be performed employing direct Monte Carlo radiation transport simulations, based on both morphological and functional images of the patient. On the other hand, for voxel dosimetry calculations the voxel S value method can be considered an easier approach than patient-specific Monte Carlo simulations, ensuring a good dosimetric accuracy at least for anatomic regions which are characterized by uniform density tissue. However, this approach has been limited because of the lack of tabulated S values for different voxel dimensions and radionuclides. The aim of this work is to provide a free dataset of values which can be used for voxel dosimetry in targeted radionuclide studies. Seven different radionuclides (89Sr, 90Y, 131I, 153Sm, 177Lu, 186Re, 188Re), and 13 different voxel sizes (2.21, 2.33, 2.4, 3, 3.59, 3.9, 4, 4.42, 4.8, 5, 6, 6.8 and 9.28 mm) are considered. Voxel S values are calculated performing simulations of monochromatic photon and electron sources in two different homogeneous tissues (soft tissue and bone) with DOSXYZnrc code, and weighting the contributions on the basis of the radionuclide emission spectra. The outcomes are validated by comparison with Monte Carlo simulations obtained with other codes (PENELOPE and MCNP4c) performing direct simulation of the radionuclide emission spectra. The differences among the different Monte Carlo codes are of the order of a few per cent when considering the source voxel and the bremsstrahlung tail, whereas the highest differences are observed at a distance close to the maximum continuous slowing down approximation range of electrons. These discrepancies would negligibly affect dosimetric assessments. The dataset of voxel S values can be freely downloaded from the website www.medphys.it.

Calculation of electron and isotopes dose point kernels with FLUKA Monte Carlo code for dosimetry in nuclear medicine therapy.

PURPOSE: The calculation of patient-specific dose distribution can be achieved by Monte Carlo simulations or by analytical methods. In this study, FLUKA Monte Carlo code has been considered for use in nuclear medicine dosimetry. Up to now, FLUKA has mainly been dedicated to other fields, namely high energy physics, radiation protection, and hadrontherapy. When first employing a Monte Carlo code for nuclear medicine dosimetry, its results concerning electron transport at energies typical of nuclear medicine applications need to be verified. This is commonly achieved by means of calculation of a representative parameter and comparison with reference data. Dose point kernel (DPK), quantifying the energy deposition all around a point isotropic source, is often the one. METHODS: FLUKA DPKS have been calculated in both water and compact bone for monoenergetic electrons (10-3 MeV) and for beta emitting isotopes commonly used for therapy (89Sr, 90Y, 131I 153Sm, 177Lu, 186Re, and 188Re). Point isotropic sources have been simulated at the center of a water (bone) sphere, and deposed energy has been tallied in concentric shells. FLUKA outcomes have been compared to PENELOPE v.2008 results, calculated in this study as well. Moreover, in case of monoenergetic electrons in water, comparison with the data from the literature (ETRAN, GEANT4, MCNPX) has been done. Maximum percentage differences within 0.8.RCSDA and 0.9.RCSDA for monoenergetic electrons (RCSDA being the continuous slowing down approximation range) and within 0.8.X90 and 0.9.X90 for isotopes (X90 being the radius of the sphere in which 90% of the emitted energy is absorbed) have been computed, together with the average percentage difference within 0.9.RCSDA and 0.9.X90 for electrons and isotopes, respectively. RESULTS: Concerning monoenergetic electrons, within 0.8.RCSDA (where 90%-97% of the particle energy is deposed), FLUKA and PENELOPE agree mostly within 7%, except for 10 and 20 keV electrons (12% in water, 8.3% in bone). The discrepancies between FLUKA and the other codes are of the same order of magnitude than those observed when comparing the other codes among them, which can be referred to the different simulation algorithms. When considering the beta spectra, discrepancies notably reduce: within 0.9.X90, FLUKA and PENELOPE differ for less than 1% in water and less than 2% in bone with any of the isotopes here considered. Complete data of FLUKA DPKS are given as Supplementary Material as a tool to perform dosimetry by analytical point kernel convolution. CONCLUSIONS: FLUKA provides reliable results when transporting electrons in the low energy range, proving to be an adequate tool for nuclear medicine dosimetry.

Recent issues on dosimetry and radiobiology for peptide receptor radionuclide therapy.

Peptide receptor radionuclide therapy (PRRT) has been constantly evolving over the last decade, providing successful results in the treatment of tumors expressing somatostatin receptors, especially with 90Y -- and 177Lu -- radiolabelled peptides. Recent and/or ongoing studies assure new perspectives to come. Dosimetry represents a precious guide for the selection of radionuclides and peptides, for protocol settings, for toxicity prevention and therapy optimization. Thus, reliable and personalized dosimetry is more and more requested. This paper reviews the important advances recently obtained in the dosimetric methods that have been applied to this therapy. Special emphasis has been given to the impact derived (or derivable in the next future) from more refined dose evaluations focused on the kidneys and the red marrow. The possibility of improving the accuracy of dosimetry represents a further challenge for this therapy. Following the preliminary correlation observed between the biological effective dose and the probability of renal injury, more reliable dose estimates could definitively enhance the predicitivity of the radiobiological effects, for toxicity prevention as well as for tumor control.

Dosimetry for treatment with radiolabelled somatostatin analogues. A review.

Peptide Receptor Radionuclide Therapy (PRRT) has proven its efficacy in the treatment of neuroendocrine and other somatostatin receptor expressing tumours (SR-tumours). Several clinical trials have confirmed that adverse effects are represented by possible renal impairment, which is the major concern, and low but not absent hematological toxicity. High kidney irradiation is a constant, despite the sparing of dose obtained by renal protectors. Hematological toxicity, although low, needs to be monitored. The clinical and dosimetry results collected in more than a decade have recognized weak points to unravel, increased knowledge, offering new views. When planning therapy with radiopeptides, the large patients' variability as for biodistribution and tumour uptake must be taken into account in order to tailor the therapy, or at least to avoid foreseeable gross treatments. Reliable and personalized dosimetry is more and more requested. This paper reviews through the literature the methods to study the biokinetics, the dosimetry outcomes, some clue information and correlations obtained once applying the radiobiological models. Special focus is given on recent improvements and indications for critical organ protection that light up challenging perspectives for PRRT.

IART (Intra-Operative Avidination for Radionuclide Therapy) for accelerated radiotherapy in breast cancer patients. Technical aspects and preliminary results of a phase II study with 90Y-labelled biotin.

BACKGROUND: Breast conserving surgery (BCS) plus external beam radiotherapy (EBRT) is considered the standard treatment for early breast cancer. We have investigated the possibility of irradiating the residual gland, using an innovative nuclear medicine approach named IART(®) (Intra-operative Avidination for Radionuclide Therapy). AIM: The objective of this study was to determine the optimal dose of avidin with a fixed activity (3.7 GBq) of (90)Y-biotin, in order to provide a boost of 20 Gy, followed by EBRT to the whole breast (WB) at the reduced dose of 40 Gy. Local and systemic toxicity, patient's quality of life, including the cosmetic results after the combined treatment with IART(®) and EBRT, were assessed. METHODS: After tumour excision, the surgeon injected native avidin diluted in 30 ml of saline solution into and around the tumour bed (see video). Patients received one of three avidin dose levels: 50 mg (10 pts), 100 mg (15 pts) and 150 mg (10 pts). Between 12 to 24 h after surgery, 3.7 GBq (90)Y-biotin spiked with 185 MBq (111)In-biotin was administered intravenously (i.v.). Whole body scans and SPECT images were performed up to 30 h post-injection for dosimetric purposes. WB-EBRT was administered four weeks after the IART(®) boost. Local toxicity and quality of life were evaluated. RESULTS: Thirty-five patients were evaluated. No side effects were observed after avidin administration and (90)Y-biotin infusion. An avidin dose level of 100 mg resulted the most appropriate in order to deliver the required radiation dose (19.5 ± 4.0 Gy) to the surgical bed. At the end of IART(®), no local toxicity occurred and the overall cosmetic result was good. The tolerance to the reduced EBRT was also good. The highest grade of transient local toxicity was G3, which occurred in 3/32 pts following the completion of WB-EBRT. The combination of IART(®)+EBRT was well accepted by the patients, without any changes to their quality of life. CONCLUSIONS: These preliminary results support the hypothesis that IART(®) may represent a valid approach to accelerated WB irradiation after BCS. We hope that this nuclear medicine technique will contribute to a better management of breast cancer patients.

Individualized dosimetry in the management of metastatic differentiated thyroid cancer.

AIM: 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. METHODS: Red marrow and lesion dosimetry (planar view) were performed during the treatment, without changing the fixed activity schema. RESULTS: 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. CONCLUSIONS: 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.

Absorbed dose and biologically effective dose in patients with high-risk non-Hodgkin's lymphoma treated with high-activity myeloablative 90Y-ibritumomab tiuxetan (Zevalin).

PURPOSE: The aim of this study was to carry out two different dose estimation approaches in patients with non-Hodgkin's lymphoma (NHL) treated with a myeloablative amount of (90)Y-labelled ibritumomab tiuxetan (Zevalin(R)) in an open-label dose escalation study. METHODS: Twenty-seven patients with relapsed/refractory or de novo high-risk NHL receiving one myeloablative dose of (90)Y-ibritumomab tiuxetan followed by tandem stem cell reinfusion were evaluated for dose estimate. The injected activity was 30 MBq/kg in 12 patients and 45 MBq/kg in 15 patients. Dose estimation was performed 1 week prior to (90)Y-ibritumomab tiuxetan by injection of (111)In-ibritumomab tiuxetan (median activity: 200 MBq). The absorbed dose (D) and the biologically effective dose (BED) were calculated. RESULTS: The absorbed doses per unit activity (Gy/GBq) were [median (range)]: heart wall 4.6 (2.5-9.7), kidneys 5.1 (2.8-10.5), liver 6.1 (3.9-10.4), lungs 2.9 (1.5-6.8), red marrow 1.0 (0.5-1.7), spleen 7.0 (1.5-14.4) and testes 4.9 (2.9-16.7). The absorbed dose (Gy) for the 15 patients treated with 45 MBq/kg were: heart wall 17.0 (8.7-25.4), kidneys 17.1 (7.9-22.4), liver 20.8 (15.4-28.3), lungs 8.1 (5.4-11.4), red marrow 3.1 (2.0-4.0), spleen 26.2 (17.0-35.6) and testes 17.3 (9.0-28.4). At the highest activities the acute haematological toxicity was mild or moderate and of very short duration, and it was independent of the red marrow absorbed dose. No secondary malignancy or treatment-related myelodysplastic syndrome was observed. No non-haematological toxicity (liver, kidney, lung) was observed during a follow-up period of 24-48 months. CONCLUSION: The use of 45 MBq/kg of (90)Y-ibritumomab tiuxetan in association with stem cell autografting resulted in patients being free of toxicity in non-haematological organs. These clinical findings were in complete agreement with our dose estimations, considering both organ doses and BED values.

Biological effective dose evaluation in gynaecological brachytherapy: LDR and HDR treatments, dependence on radiobiological parameters, and treatment optimisation.

PURPOSE: This study was undertaken to compare the biological efficacy of different high-dose-rate (HDR) and low-dose-rate (LDR) treatments of gynaecological lesions, to identify the causes of possible nonuniformity and to optimise treatment through customised calculation. MATERIALS AND METHODS: The study considered 110 patients treated between 2001 and 2006 with external beam radiation therapy and/or brachytherapy with either LDR (afterloader Selectron, (137)Cs) or HDR (afterloader microSelectron Classic, (192)Ir). The treatments were compared in terms of biologically effective dose (BED) to the tumour and to the rectum (linear-quadratic model) by using statistical tests for comparisons between independent samples. RESULTS: The difference between the two treatments was statistically significant in one case only. However, within each technique, we identified considerable nonuniformity in therapeutic efficacy due to differences in fractionation schemes and overall treatment time. To solve this problem, we created a Microsoft Excel spreadsheet allowing calculation of the optimal treatment for each patient: best efficacy (BED(tumour)) without exceeding toxicity threshold (BED(rectum)). CONCLUSIONS: The efficacy of a treatment may vary as a result of several factors. Customised radiobiological evaluation is a useful adjunct to clinical evaluation in planning equivalent treatments that satisfy all dosimetric constraints.

Application of the platelet count/spleen diameter ratio to rule out the presence of oesophageal varices in patients with cirrhosis: a validation study based on follow-up.

BACKGROUND: Screening for oesophageal varices represents an important part of the diagnostic work-up of cirrhotic patients. We have previously shown that the platelet count/spleen diameter ratio is a parameter that can rule out the presence of oesophageal varices safely and in a cost-effective fashion. AIM: To evaluate the prognostic and diagnostic accuracy of the platelet count/spleen diameter ratio for ruling out the presence of oesophageal varices in the follow-up of a cohort of cirrhotic patients without oesophageal varices at inclusion. METHODS: After initial endoscopy, the 106 cirrhotic patients without oesophageal varices who participated in our previous study were followed-up with annual or biannual surveillance endoscopy. Patients were censored at the time of diagnosis of oesophageal varices or at their last visit, and at that time platelet count and spleen diameter were recorded. Sixty-eight patients made up the study cohort after excluding patients who were lost to follow-up or died before undergoing control endoscopy. RESULTS: During the follow-up, 27 patients (40%) developed oesophageal varices. Patients with higher baseline platelet count/spleen diameter ratios (p<0.0001) as well as a ratio above 909 were less likely to develop oesophageal varices (p<0.0005). At follow-up, a platelet count/spleen diameter ratio < or = 909 had 100% negative predictive value and 84% efficiency in identifying the presence of oesophageal varices. CONCLUSIONS: The use of the platelet count/spleen diameter ratio proved to be an effective means for ruling out the presence of oesophageal varices even in the longitudinal follow-up of patients.

Prognosis of hepatocellular carcinoma in anti-HCV positive cirrhotic patients: a single-centre comparison amongst four different staging systems.

BACKGROUND: Epidemiological studies have foreseen an increase in the incidence of hepatocellular carcinoma (HCC) in the near future and it is estimated that this trend will mostly affect hepatitis C virus (HCV) positive cirrhotic patients. Therefore, accuracy of HCC staging is an important clinical issue. AIM: To investigate the prognostic usefulness of a series of newly proposed HCC prognostic systems such as the Cancer of the Liver Italian Program (CLIP) score, the Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire (GRETCH) model and the Barcelona Clinic Liver Cancer (BCLC) staging classification when compared with the usefulness of a known staging system such as the Okuda staging system in a group of anti-HCV positive cirrhotic patients with HCC seen at a single centre. METHODS: Okuda stage, CLIP score, GRETCH model and BCLC stages were retrospectively computed in 81 anti-HCV positive cirrhotic patients with HCC. We evaluated and compared the ability of these methods to assess survival prognosis. RESULTS: As of December 2001, 51 patients had died and overall median survival was 18 months. All the staging systems were able to identify various patient subgroups with different survival. The CLIP score, the GRETCH model and the BCLC staging classification were better at characterizing the 1-year prognosis of the patients when compared with the Okuda staging system, whilst the 3-year prognostic evaluation was improved only by using the CLIP score or the BCLC staging classification. CONCLUSIONS: The prognostic value and usefulness of the CLIP score, the GRETCH model and the BCLC staging classification was reproduced in a single-centre analysis of anti-HCV positive HCC cirrhotic patients. These scores provided a prognostic assessment of our patients which is superior to what was obtained by the Okuda staging system.

Platelet count/spleen diameter ratio: proposal and validation of a non-invasive parameter to predict the presence of oesophageal varices in patients with liver cirrhosis.

BACKGROUND AND AIMS: Cirrhotic patients frequently undergo screening endoscopy for the presence of oesophageal varices (OV). In the future, this social and medical burden will increase due to the greater number of patients with chronic liver disease and their improved survival. In this study, our aims were (1) to identify clinical, biochemical, and ultrasonographic parameters which might non-invasively predict the presence of OV in patients with liver cirrhosis; (2) to evaluate the reproducibility of the obtained results in a different, although related, further group of patients; and (3) to assess the predictiveness of the identified rules in patients with compensated cirrhosis. METHODS: In the first part of the study we retrospectively evaluated the presence of OV in 145 cirrhotic patients, and in the second part we evaluated the reproducibility of the study results in a subsequent group of 121 patients. Finally, we evaluated these parameters in a subgroup of 145 patients with compensated disease. All 266 patients underwent a complete biochemical workup, upper digestive endoscopy, and ultrasonographic measurement of spleen bipolar diameter. Platelet count/spleen diameter ratio was calculated for all patients. RESULTS: The prevalence rates of OV were 61% and 58% in the first and second groups of patients, respectively. In the first part of the study, we found that platelet count, spleen diameter, platelet count/spleen diameter ratio, and Child- Pugh class were significantly different among patients with or without OV, although the platelet count/spleen diameter ratio was the only parameter which was independently associated with the presence of OV in a multivariate analysis. A platelet count/spleen diameter ratio cut off value of 909 had 100% negative predictive value for a diagnosis of OV. This result was reproduced in the second group of patients as well as in patients with compensated disease. In a cost-benefit analysis, screening cirrhotic patients according to the "platelet count/spleen diameter ratio strategy" was far more cost effective compared with the "scope all strategy". CONCLUSIONS: The platelet count/spleen diameter ratio is the only parameter which is independently associated with the presence of OV, and its negative predictive value is reproducible. Its use is of value even in the subgroup of patients with compensated disease, and it is also cost effective.

Trans-catheter arterial chemoembolisation for hepatocellular carcinoma in patients with viral cirrhosis: role of combined staging systems, Cancer Liver Italian Program (CLIP) and Model for End-stage Liver Disease (MELD), in predicting outcome after treatment.

BACKGROUND: Trans-catheter arterial chemoembolisation (TACE) is the most common palliative treatment for hepatocellular carcinoma (HCC). The therapeutic options depend both on the characteristics of the tumour and on functional staging of the cirrhosis. AIM: To evaluate the effects of TACE on the survival of cirrhotic patients with HCC according to different staging systems [Okuda score, Cancer Liver Italian Program (CLIP) score, Model for End-stage Liver Disease (MELD) score] and in relation to the side-effects of TACE. METHODS: Fifty cirrhotic patients, 36 CTP class A and 14 class B, underwent 106 TACE treatments with mitoxantrone. Survival at 12, 24, and 36 months was evaluated. RESULTS: MELD at 12 months and CLIP at 24 months were identified as significant variables associated with survival. Combined cut-offs of CLIP and of MELD identified four subgroups of patients with different survivals, at 12, 24 and 36 months, respectively: CLIP >or= 2 and MELD >or= 10 (63%, 20% and 0%), CLIP < 2 and MELD >or= 10 (73%, 40% and 22%), CLIP >or= 2 and MELD < 10 (73%, 40% and 22%) and CLIP < 2 and MELD < 10 (100%, 63% and 50%). Post-TACE side-effects proved to have no influence on survival. CONCLUSION: In patients with poor probability of survival (CLIP >or= 2 and MELD >or= 10), TACE must be planned with a great deal of caution, while in patients with possibly good outcomes (CLIP < 2 and MELD < 10), more 'aggressive' therapy should be taken into consideration.