Long-term disease outcome and volume-based decision strategy in a large cohort of multiple brain metastases treated with a mono-isocentric linac-based Stereotactic Radiosurgery technique.

PURPOSE: Radiosurgery (SRS) is an effective treatment option for brain metastases (BMs). Long-term results of the first worldwide experience with a mono-isocentric, non-coplanar, linac-based stereotactic technique in the treatment of multiple BMs are reported. METHODS: patients with multiple BMs, life expectancy > 3 months, and good performance status (≤ 2) were treated with simultaneous SRS with volumetric modulated arc technique. Data were retrospectively evaluated. RESULTS: 172 patients accounting for 1079 BMs were treated at our institution from 2017 to 2020. The median number of treated metastases was 4 (range 2-22). Primary tumor histology was: lung (44.8%), breast (32%), and melanoma (9.4%). The 2-year LPFS was 71.6%, respectively. A biological effective dose (BED) ≥ 51.3 Gy10 correlated with higher local control. Uncontrolled systemic disease and melanoma histology were independent prognostic factors correlated with decreased iPFS. Patients with > 10 BMs had a trend towards shorter iPFS (p = 0.055). 31 patients received multiple SRS courses (2-7) in case of intracranial progression. The median iOS was 22.4 months. Brainstem metastases and total PTV > 7.1 cc correlated with shorter iOS. The 1- and 2-year WBRT-free survival was 83.2% and 61.1%, respectively. CONCLUSION: Long-term results in a large patient population treated with a mono-isocentric, dedicated technique demonstrated its effectiveness and safety also in the case of multiple courses. The shortened treatment time and the possibility to safely spare healthy brain tissue allows the safe treatment of patients with a large number of metastases and to deliver multiple courses of SRS. In selected cases, the administration of WBRT can be delayed.

Applying radiobiological plan ranking methodology to VMAT prostate SBRT.

The impact of a rectal spacer and an increased near maximum target dose in VMAT prostate SBRT is studied. For a group of 11 patients (35Gy-in-five-fractions VMAT prostate SBRT) a set of 4 plans were generated, namely two VMAT plans, with D2%⩽37.5Gy (Hom) and with D2%⩽40.2Gy (Het), were created for each of two CT scans taken before (NoSpc) and after (Spc) transperineal spacer insertion. Consequently the methodology for parameter invariant TCP (tumor control probability) plan ranking was applied for comparison of the plans in terms of tumor control. NTCPs (normal tissue complication probabilities) were calculated for rectum and bladder using Lyman's model. For all 11 patients the TCP plan ranking has shown that the Het plans would perform considerably better in TCP terms than the Hom ones. The plans without rectal spacer were ranked worse compared to those with rectal spacer except for one set of Hom plans. The calculated NTCPs for rectum produced by the Het plans were quite similar to the NTCPs of the Hom ones. The rectal NTCPs of the Hom Spc plans were always lower than the NTCPs of the Hom NoSpc plans. The NTCP values for bladder were extremely low in all cases. The use of rectal spacer leads in general to lower risk of rectal complications, as expected, and even to better tumor control. Plans with increased near maximum target dose (D2%⩽40.2Gy) are expected to perform much better in terms of tumor control than those with D2%⩽37.5Gy.

The impact of prostate gland dimension in genitourinary toxicity after definitive prostate cancer treatment with moderate hypofractionation and volumetric modulated arc radiation therapy

Purpose: To analyze clinical-dosimetric predictors of genitourinary (GU) toxicity in a cohort of prostate cancer (PC) patients treated with moderate hypofractionation and simultaneous integrated boost (SIB) using volumetric modulated arc therapy (VMAT) technique. Materials and methods: 60 patients were selected. Patients were stratified into low (43 %), intermediate (30 %) and high-risk (27 %) groups. Low-risk patients received 73.5 Gy to PTV1; intermediate-risk received 73.5 Gy to PTV1 and 60 Gy to PTV2; high-risk received 73.5 Gy to PTV1, 60 Gy to PTV2, and 54 Gy to PTV3. All patients were treated in 30 fractions. Androgen deprivation therapy (ADT) was prescribed upfront in intermediate and high-risk categories. Toxicity was scored according to Common Terminology Criteria for Adverse Events v4.0 scoring system. Results: Median follow-up was 30 months (range 16-36 months). GU acute toxicity was recorded as followS: G0 = 16/60 (27 %), G1 = 18/60 (30 %); G2 = 26/ 60 (43 %). GU late toxicity was recorded as follows: G0 = 20/60 (34 %); G1 = 29/60 (48 %); G2 = 11/56 (18 %). The risk of acute G2 GU toxicity was three times higher for prostate volume C80 cc. In 60 % of the patients with a prostate volume C80 cc, the first 3 weeks are at particular risk for toxicity onset. In the late setting, no statistical significance was found between GU toxicity and prostate gland dimension. Conclusion: Prostate volume C80 cc resulted a predictive factor of acute G2 GU toxicity, in moderate hypofractionation and volumetric modulated arc radiation therapy for definitive PC (AU)

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The impact of prostate gland dimension in genitourinary toxicity after definitive prostate cancer treatment with moderate hypofractionation and volumetric modulated arc radiation therapy.

PURPOSE: To analyze clinical-dosimetric predictors of genitourinary (GU) toxicity in a cohort of prostate cancer (PC) patients treated with moderate hypofractionation and simultaneous integrated boost (SIB) using volumetric modulated arc therapy (VMAT) technique. MATERIALS AND METHODS: 60 patients were selected. Patients were stratified into low (43 %), intermediate (30 %) and high-risk (27 %) groups. Low-risk patients received 73.5 Gy to PTV1; intermediate-risk received 73.5 Gy to PTV1 and 60 Gy to PTV2; high-risk received 73.5 Gy to PTV1, 60 Gy to PTV2, and 54 Gy to PTV3. All patients were treated in 30 fractions. Androgen deprivation therapy (ADT) was prescribed upfront in intermediate and high-risk categories. Toxicity was scored according to Common Terminology Criteria for Adverse Events v4.0 scoring system. RESULTS: Median follow-up was 30 months (range 16-36 months). GU acute toxicity was recorded as followS: G0 = 16/60 (27 %), G1 = 18/60 (30 %); G2 = 26/60 (43 %). GU late toxicity was recorded as follows: G0 = 20/60 (34 %); G1 = 29/60 (48 %); G2 = 11/56 (18 %). The risk of acute G2 GU toxicity was three times higher for prostate volume ≥80 cc. In 60 % of the patients with a prostate volume ≥80 cc, the first 3 weeks are at particular risk for toxicity onset. In the late setting, no statistical significance was found between GU toxicity and prostate gland dimension. CONCLUSION: Prostate volume ≥80 cc resulted a predictive factor of acute G2 GU toxicity, in moderate hypofractionation and volumetric modulated arc radiation therapy for definitive PC.

Intensity modulated radiation therapy with simultaneous integrated boost in early breast cancer irradiation. Report of feasibility and preliminary toxicity.

PURPOSE: To investigate the feasibility and tolerance in the use of adjuvant intensity modulated radiation therapy (IMRT) and simultaneous integrated boost in patients with a diagnosis of breast cancer after breast-conserving surgery. PATIENTS AND METHODS: Between September 2011 to February 2013, 112 women with a diagnosis of early breast cancer (T1-2, N0-1, M0) were treated with IMRT and simultaneous integrated boost after breast-conserving surgery in our institution. A dose of 50Gy in 25 fractions was prescribed to the whole breast and an additional dose of radiation was prescribed on the tumour bed. A dose prescription of 60Gy in 25 fractions to the tumour bed was used in patients with negative margins after surgery, whereas if the margins were close (<1mm) or positive (without a new surgical resection) a dose of 64Gy was prescribed. All patients were followed with periodic clinical evaluation. Acute and late toxicity were scored using the EORTC/RTOG radiation morbidity score system. Both patient and physician recorded cosmetic outcome evaluation with a subjective judgment scale at the time of scheduled follow-up. RESULTS: The median follow-up was 28 months (range 24-40 months). The acute skin grade toxicity during the treatment was grade 0 in 8 patients (7%), grade 1 in 80 (72%), grade 2 in 24 cases (21%). No grade 3 or higher acute skin toxicity was observed. At 12 months, skin toxicity was grade 0 in 78 patients (70%), grade 1 in 34 patients (30%). No toxicity grade 2 or higher was registered. At 24 months, skin toxicity was grade 0 in 79 patients (71%), grade 1 in 33 patients (29%). No case of grade 2 toxicity or higher was registered. The pretreatment variables correlated with skin grade 2 acute toxicity were adjuvant chemotherapy (P=0.01) and breast volume ≥700cm(3) (P=0.001). Patients with an acute skin toxicity grade 2 had a higher probability to develop late skin toxicity (P<0.0001). In the 98% of cases, patients were judged to have a good or excellent cosmetic outcome. The 2-year-overall survival and 2-year-local control were 100%. CONCLUSION: These data support the feasibility and safety of IMRT with simultaneous integrated boost in patients with a diagnosis of early breast cancer following breast-conserving surgery with acceptable acute and late treatment-related toxicity. A longer follow-up is needed to define the efficacy on outcomes.

Enzymatic transesterification of waste vegetable oil to produce biodiesel.

An experimental study on enzymatic transesterification was performed to produce biodiesel from waste vegetable oils. Lipase from Pseudomonas cepacia was covalently immobilized on a epoxy-acrylic resin support. The immobilized enzyme exhibited high catalytic specific surface and allowed an easy recovery, regeneration and reutilisation of biocatalyst. Waste vegetable oils - such as frying oils, considered not competitive with food applications and wastes to be treated - were used as a source of glycerides. Ethanol was used as a short chain alcohol and was added in three steps with the aim to reduce its inhibitory effect on lipase activity. The effect of biocatalyst/substrate feed mass ratios and the waste oil quality have been investigated in order to estimate the process performances. Biocatalyst recovery and reuse have been also studied with the aim to verify the stability of the biocatalyst for its application in industrial scale.

Dose-volume-related dysphagia after constrictor muscles definition in head and neck cancer intensity-modulated radiation treatment.

OBJECTIVE: Dysphagia remains a side effect influencing the quality of life of patients with head and neck cancer (HNC) after radiotherapy. We evaluated the relationship between planned dose involvement and acute and late dysphagia in patients with HNC treated with intensity-modulated radiation therapy (IMRT), after a recontouring of constrictor muscles (PCs) and the cricopharyngeal muscle (CM). METHODS: Between December 2011 and December 2013, 56 patients with histologically proven HNC were treated with IMRT or volumetric-modulated arc therapy. The PCs and CM were recontoured. Correlations between acute and late toxicity and dosimetric parameters were evaluated. End points were analysed using univariate logistic regression. RESULTS: An increasing risk to develop acute dysphagia was observed when constraints to the middle PCs were not respected [mean dose (Dmean) ≥50 Gy, maximum dose (Dmax) >60 Gy, V50 >70% with a p = 0.05]. The superior PC was not correlated with acute toxicity but only with late dysphagia. The inferior PC was not correlated with dysphagia; for the CM only, Dmax >60 Gy was correlated with acute dysphagia ≥ grade 2. CONCLUSION: According to our analysis, the superior PC has a major role, being correlated with dysphagia at 3 and 6 months after treatments; the middle PC maintains this correlation only at 3 months from the beginning of radiotherapy, but it does not have influence on late dysphagia. The inferior PC and CM have a minimum impact on swallowing symptoms. ADVANCES IN KNOWLEDGE: We used recent guidelines to define dose constraints of the PCs and CM. Two results emerge in the present analysis: the superior PC influences late dysphagia, while the middle PC influences acute dysphagia.

Prevalence and incidence of cluster headache in the Republic of San Marino.

Based on a preceding survey performed in 1985, the authors estimated the prevalence and incidence of cluster headache (CH) in the Republic of San Marino (26,628 inhabitants at 31 December 1999). All cases were diagnosed by direct interview according to International Headache Society criteria. The prevalence rate was 56/100,000 (95% CI 31.3 to 92.4), and the incidence rate was 2.5/100,000/year (95% CI 1.14 to 4.75). Most cases showed rare clusters. This is the first prospective study on the incidence of CH.

[Spontaneous dissection of the left main coronary artery: a case report and review of the literature]. / Dissezione spontanea del tronco comune della coronaria sinistra: un case clinico e revisione della letteratura.

Primary spontaneous coronary artery dissection occurs rarely. Compared to usual acute coronary syndromes, it occurs in relatively young people, particularly in women in the peripartum or early post-partum period. The etiology of spontaneous coronary artery dissection remains unclear; there have been less than 150 cases reported in the literature, and only 28 cases documented in the left main coronary artery. This article reports the clinical course of a patient with primary spontaneous left main coronary artery dissection who was treated with coronary artery bypass grafting after clinical steadiness.

Angioarchitectural arrangements in corrosion cast of the nasal septum of the Mongolian gerbil.

The three-dimensional architecture of the vascular network of the nasal septum of the gerbil rat was studied using the corrosive resin cast technique. The angioarchitecture of the nasal septum observed with scanning electron microscopy (SEM) showed that a vascular network is disposed in the lamina propria. The capillaries, arterioles, venules and arteries were closely observed in different areas of the nasal septum mucosa.

[Clinical and echocardiographic evaluation of thalassemic cardiomyopathy]. / Valutazione clinica ed ecocardiografica della cardiomiopatia talassemica.

To evaluate the reliability of the echocardiographic examination in assessment of adult patient with thalassemia major, in comparison with clinical, electrocardiographic and/or chest x ray exams, 103 patients with thalassemia major, mean age 20 years (range 14 to 30 years), were studied and compared with 30 age matched normal subjects. All patients were receiving transfusions regularly to maintain hemoglobin levels above 11 g/dl and subcutaneous infusions of desferrioxamine (about 40 mg/kg/day) to reduce hemosiderosis. The patients were divided into three groups according to their cardiac impairment, deduced by clinical history, electrocardiography (ECG) and/or chest x ray. Group I (36 patients) showed no signs or symptoms of cardiac impairment. Group II (38 patients) had only signs of cardiac impairment by ECG and/or chest x ray. Group III (29 patients) had both symptoms and signs of cardiac failure. In comparison to normal controls, Group I showed an increase in left ventricular (LV) dimension (EDD) and mass (p < 0.001), Group II and III showed a decrease in LV fractional shortening (FS; p < 0.001) too. In comparison to Group I, Group II showed a decrease in LV FS (p < 0.05), Group III showed an increase in LV EDD and mass (p < 0.001) too. In comparison to Group II, Group III showed an increase in LV EDD and mass (p < 0.001), and a decrease in LV FS (p < 0.001). In conclusion, echocardiographic examination appears a tool more reliable than clinical, electrocardiographic and/or chest x ray examination in assessment of adult patient with thalassemia major.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo metabolic studies of glucose, ATP and 2,3-DPG in beta-thalassaemia intermedia, heterozygous beta-thalassaemic and normal erythrocytes: 13C and 31P MRS studies.

13C and 31P magnetic resonance spectroscopy was used to characterize the in vivo kinetics of glucose metabolism and intracellular ATP and 2,3-DPG concentrations in erythrocytes obtained from beta-thalassaemia intermedia, heterozygous beta-thalassaemic and normal individuals and maintained in suspension. Except for an upfield chemical shift in the 2P and 3P resonance of 2,3-DPG in the thalassaemia intermedia erythrocytes, the 31P spectra were comparable between all three blood types, showing similar concentrations of ATP (from 4.5 to 5.2 mumol/g Hb) and 2,3-DPG (from 17.2 to 19.7 mumol/g Hb). However, the profile of glucose metabolism was quite different in beta-thalassaemia intermedia erythrocytes, whereas glucose was consumed at a rate of 0.089 +/- 0.035 fmol/cell/h, significantly higher than that of normal (0.032 +/- 0.018 fmol/cell/h; P = 0.01) and heterozygous (0.025 +/- 0.004 fmol/cell/h; P = 0.01) erythrocytes. This near 3-fold faster rate of glucose metabolism in the thalassaemia intermedia erythrocytes could not be accounted for by any increase in glucose flux via the Embden-Meyerhof pathway, since no significant difference in 3-13C-lactate synthesis was observed among the three blood types (in units of fmol/cell/h, normal, 0.021 +/- 0.013; heterozygous, 0.021 +/- 0.006; beta-thalassaemia intermedia 0.045 +/- 0.025). These results reflect an accelerated rate of glucose metabolism in thalassaemia intermedia erythrocytes because the contribution of reticulocytes to this altered pattern of metabolism could be excluded. As the only other route of glucose metabolism in erythrocytes is the pentose phosphate pathway (PPP), these results indicate that the PPP is more active in beta-thalassaemia intermedia erythrocytes, perhaps as a consequence of their elevated intracellular oxidative state.

Prevalence of Parkinson's disease in the Republic of San Marino.

A prevalence survey on Parkinson's disease (PD) was performed in the Republic of San Marino, which is the smallest independent state in the world, and is located near the Adriatic coast, within Italy. On April 30, 1986, it had a population of 22,322. We found 34 cases of PD (17 men, 17 women). Crude prevalence ratio per 100,000 population was 152 (154 for men, 150 for women) with an age-adjusted ratio of 185 (both sexes). This study shows that the prevalence of PD in the Mediterranean area of South Europe is similar to that in North Europe and the United States.

Multiple sclerosis in the Republic of San Marino.

Previous studies on the prevalence of multiple sclerosis in Italy have grossly underestimated the prevalence of the disease. The prevalence in the Republic of San Marino (near Rimini), in Sicily, and no doubt in the rest of Italy, is of the same order of magnitude as in Europe--that is, 40-60/100 000. The contrast of this with the very low prevalence in Malta (only 60 miles (96 km) away from Sicily) of 4/100 000 should provide a clue to the genetic and environmental factors responsible for multiple sclerosis.