A multi-institutional analysis of fractionated versus single-fraction stereotactic body radiotherapy (SBRT) in the treatment of primary lung tumors: a comparison between two antipodal fractionations

Objectives Stereotactic body radiotherapy (SBRT) is a consolidate treatment for inoperable early-stage lung tumors, usually delivered in single or multi-fraction regimens. We aimed to compare these two approaches in terms of local effectiveness, safety and survival. Materials and methods Patients affected by medically inoperable early-stage lung tumor were treated at two Institutions with two different schedules: 70 Gy in ten fractions (TF) (BED10: 119 Gy) or 30 Gy in single fraction (SF) (BED10: 120 Gy). Results 73 patients were treated with SBRT delivered with two biological equivalent schedules: SF (44) and TF (29). The median follow-up was 34 months (range 3–81 months). Three-year Overall survival (OS) was 57.9%, 3-year cancer-specific survival (CSS) was 77.2%, with no difference between treatment groups. Three-year progression-free survival (LPFS) was 88.9% and did not differs between SF and TF. Overall, four cases (5.4%) of acute grade ≥ 3 pneumonitis occurred. No differences in acute and late toxicity between the two groups were detected. Conclusion SF and TF seems to be equally safe and effective in the treatment of primary inoperable lung tumors especially for smaller lesion. The SF may be preferentially offered to reduce patient access to hospital with no negative impact on tumor control and survival (AU)

A multi-institutional analysis of fractionated versus single-fraction stereotactic body radiotherapy (SBRT) in the treatment of primary lung tumors: a comparison between two antipodal fractionations.

OBJECTIVES: Stereotactic body radiotherapy (SBRT) is a consolidate treatment for inoperable early-stage lung tumors, usually delivered in single or multi-fraction regimens. We aimed to compare these two approaches in terms of local effectiveness, safety and survival. MATERIALS AND METHODS: Patients affected by medically inoperable early-stage lung tumor were treated at two Institutions with two different schedules: 70 Gy in ten fractions (TF) (BED10: 119 Gy) or 30 Gy in single fraction (SF) (BED10: 120 Gy). RESULTS: 73 patients were treated with SBRT delivered with two biological equivalent schedules: SF (44) and TF (29). The median follow-up was 34 months (range 3-81 months). Three-year Overall survival (OS) was 57.9%, 3-year cancer-specific survival (CSS) was 77.2%, with no difference between treatment groups. Three-year progression-free survival (LPFS) was 88.9% and did not differs between SF and TF. Overall, four cases (5.4%) of acute grade ≥ 3 pneumonitis occurred. No differences in acute and late toxicity between the two groups were detected. CONCLUSION: SF and TF seems to be equally safe and effective in the treatment of primary inoperable lung tumors especially for smaller lesion. The SF may be preferentially offered to reduce patient access to hospital with no negative impact on tumor control and survival.

Local and metastatic curative radiotherapy in patients with de novo oligometastatic prostate cancer.

The aim of this observational study is to investigate whether local consolidative treatment delivered to the primary site and metastatic tumour burden may add survival benefit to de novo oligometastatic prostate cancer (Oligo-PCa) patients. We retrospectively reviewed all Oligo-PCa patients treated with radiotherapy to the primary tumor sites and metastatic tumor burden at our institution between March 2010 and June 2019. All patients having ≤ 5 metastases involving nodes and/or bones, loco-regional and/or extra-pelvic sites, were included. Most of the patients had started androgen deprivation therapy with or without docetaxel as standard of care before radiotherapy. The Kaplan Meier analysis was performed to estimate survival outcomes. The univariate analysis tested possible prognostic factors increasing the rate of biochemical relapse. We analysed 37 Oligo-PCa patients. Twenty-eight (75.7%) had loco-regional metastases, in 9 patients (24.3%) the metastatic tumour burden was extra-pelvic. Nineteen (51.4%) had bone metastases, 21 (56.8%) nodal involvement and 7 (18.9%) both. Twenty (54.1%) had a single metastasis. The median follow-up was 55.5 months. The median overall survival (OS) was 68.8 months, the 2- and 5-year OS rates were 96.9% and 65.4%. The median biochemical relapse free survival (b-RFS) was 58 months and the 2- and 5-year b-RFS rates were 73.3% and 39.3%. The 2- and 5-year local relapse free survival rates were 93.9% and 83.7%. On the univariate analysis post-treatment PSA level ≤ 1 ng/ml was significantly related with the b-RFS (p = 0.004). Curative approach in Oligo-PCa patients involving both the primary tumor and metastatic sites may be feasible and well tolerate. Many patients presented longer survival and PSA at first follow-up was the most important prognostic factor. Further trials are needed to confirm our results and to evaluate if patients with PSA at first follow-up > 1 ng/ml may benefit from further treatments.

Salvage radiotherapy with simultaneous integrated boost in non small-cell lung cancer patients with mediastinal relapse after surgery: a pilot study.

BACKGROUND: The aim of our study was to evaluate feasibility, toxicity profile and local control of salvage intensity modulated radiotherapy (IMRT) delivered with simultaneous integrated boost (SIB) associated or not to concomitant weekly cisplatin in patients affected by NSCLC with mediastinal nodal recurrence after surgery. Patterns of recurrence, outcomes and prognostic factors were assessed. METHODS: Fourteen consecutive patients received 25 fractions of 50Gy/2Gy to the elective nodal stations and boost up to 62.5Gy/2.5Gy to the macroscopic lymph node metastases. Concomitant weekly cisplatin (40 mg/m2) was administered to 8 (57.1%) patients. RESULTS: Five (35.7%) patients experienced grade 2 pneumonitis and 5 (35.7%) patients had grade 2 esophagitis. One case of grade 3 pneumonitis occurred and was successfully treated with antibiotics and steroids with no sequelae. No patient recurred locally in the boost volume (local control 100%). Loco-regional control was 79% with 3 patients that developed nodal recurrence principally marginal to the elective volume. Seven patients developed distant metastases. Median PFS was 7 months. The nodal involvement of station 7 was associated to a significantly lower median metastasis-free survival (4 months vs. not reached, p = 0.036). CONCLUSIONS: Salvage radiotherapy with IMRT-SIB is a feasible and a well-tolerated treatment option for mediastinal recurrent NSCLC after surgery. The role of more intensified radiation regimens and association to systemic therapy remain to be evaluated in larger cohorts.

30 Gy single dose stereotactic body radiation therapy (SBRT): Report on outcome in a large series of patients with lung oligometastatic disease.

OBJECTIVES: To evaluate the local control (LC) and long term adverse effects in a series of patients with lung metastases who received 30 Gy in single dose with stereotactic technique. MATERIALS AND METHODS: Between December 2008 and April 2016, a total of 166 lung metastases in 129 patients affected by oligometastatic disease were treated at our Institution with stereotactic body radiotherapy (SBRT). Mainly, the primary tumors were non small-cell lung cancer and colorectal cancer (45.2% and 28.8%, respectively). Prognostic factors were also assessed. RESULTS: The median follow-up was 38 months. Local progression occurred in 24 (14.4%) lesions in 21 patients. Intra-thoracic progression (new lung lesions or thoracic lymph node metastases) occurred in 59 (45.7%) patients. Forty-five (34.8%) patients had distant progression after a median time of 14 months. The 3- and 5-years local relapse-free survival (LPFS) were 80.1% and 79.2% (median not reached), respectively. One-hundred forty-eight patients were evaluated for late toxicity (follow-up >6 months): 51 (34.4%) patients had grade ≤2 fibrosis, 11 (7.4%) patients experienced grade 3 fibrosis. Two (1.3%) cases of rib fracture occurred. One case of toxic death (grade 5) has been reported. Median OS was 39 months. At the univariate analysis, lesion diameter ≤18 mm correlated significantly with a longer LPFS (p = 0.001). At the multivariate analysis, lesion diameter <18 mm was predictive for longer LPFS (p = 0.006). Also, oligometastases from primary colorectal cancer was a significant predictive factor for worse LPFS (p = 0.041) and progression-free survival (p = 0.04). CONCLUSIONS: To our knowledge, the current study represents the largest series on the use of SBRT 30 Gy single dose for lung metastases. Our results confirm the effectiveness and safety of this schedule administered in selected oligometastatic patients. Further prospective series could better validate these results.

The neural correlates of road sign knowledge and route learning in semantic dementia and Alzheimer's disease.

BACKGROUND: Although there is a growing body of research on driving and Alzheimer's disease (AD), focal dementias have been understudied. Moreover, driving has never been explored in semantic dementia (SD). METHODS: An experimental battery exploring road sign knowledge and route learning was applied to patients with SD and AD selected in the early-moderate stage of disease and to a group of healthy participants. Neuropsychological data were correlated to cerebral hypometabolism distribution, investigated by means of positron emission tomography. RESULTS: The two dementias showed opposite profiles. Patients with SD showed poor road sign knowledge and normal performance in route learning. By contrast, patients with AD showed low performance in route learning test with preservation of semantic knowledge of road signs. In SD, there was a correlation of semantic knowledge impairment with hypometabolism in the left temporolateral cortex. No correlation between the AD region of interests (ROIs) and the relevant behavioural indices was found, while in the whole-brain analysis there was a significant correlation between route learning and the superior frontal gyrus. DISCUSSION AND CONCLUSIONS: For the first time, driving skills were explored in SD, and it is showed a differential profile from the one detected in AD. We demonstrate that the left anterior temporal cortex is implicated in road sign knowledge, while a distributed cortical network, including the frontal cortex, is likely to process route learning.

Stress-ECG vs. CT coronary angiography for the diagnosis of coronary artery disease: a "real-world" experience.

PURPOSE: This study aimed to evaluate the diagnostic accuracy of stress electrocardiogram (ECG) and computed tomography coronary angiography (CTCA) for the detection of significant coronary artery stenosis (> or =50%) in the real world using conventional CA as the reference standard. MATERIALS AND METHODS: A total of 236 consecutive patients (159 men, 77 women; mean age 62.8+/-10.2 years) at moderate risk and with suspected coronary artery disease (CAD) were enrolled in the study and underwent stress ECG, CTCA and CA. The CTCA scan was performed after i.v. administration of a 100-ml bolus of iodinated contrast material. The stress ECG and CTCA reports were used to evaluate diagnostic accuracy compared with CA in the detection of significant stenosis > or =50%. RESULTS: We excluded 16 patients from the analysis because of the nondiagnostic quality of stress ECG and/or CTCA. The prevalence of disease demonstrated at CA was 62% (n=220), 51% in the population with comparable stress ECG and CTCA (n=147) and 84% in the population with equivocal stress ECG (n=73). Stress ECG was classified as equivocal in 73 cases (33.2%), positive in 69 (31.4%) and negative in 78 (35.5%). In the per-patient analysis, the diagnostic accuracy of stress ECG was sensitivity 47%, specificity 53%, positive predictive value (PPV) 51% and negative predictive value (NPV) 49%. On stress ECG, 40 (27.2%) patients were misclassified as negative, and 34 (23.1%) patients with nonsignificant stenosis were overestimated as positive. The diagnostic accuracy of CTCA was sensitivity 96%, specificity 65%, PPV 74% and NPV 94%. CTCA incorrectly classified three (2%) as negative and 25 (17%) as positive. The difference in diagnostic accuracy between stress ECG and CTCA was significant (p<0.01). CONCLUSIONS: CTCA in the real world has significantly higher diagnostic accuracy compared with stress ECG and could be used as a first-line study in patients at moderate risk.

Tako-Tsubo cardiomyopathy with coronary artery stenosis: a case-series challenging the original definition.

We report a case-series of seven patients with Tako-Tsubo cardiomyopathy (TTC) and at least one concomitant >or=50% coronary stenosis. Each case involves a female patient who presented symptoms and an electrocardiogram compatible with acute coronary syndrome, mild troponin I elevation, a ventriculogram showing left ventricle (LV) apical or midventricular ballooning (classical or variant TTC), an angiogram showing at least one >or=50% stenosis and a cardiac magnetic resonance showing no myocardial late Gadolinium enhancement. Full recovery of normal LV contractility after the event was required to confirm TTC. Our report presents the case for the opportunity to modify the TTC definition, removing the requirement for absence of coronary stenosis not to exclude patients with bystander coronary lesions, who are probably under diagnosed as per the original TTC definition.

64-slice computed tomography coronary angiography: diagnostic accuracy in the real world.

PURPOSE: This study was done to evaluate the diagnostic accuracy of 64-slice computed tomography coronary angiography (CTCA) for the detection of significant coronary artery stenosis in the real clinical world. MATERIALS AND METHOD: From the CTCA database of our institution, we enrolled 145 patients (92 men, 52 women, mean age 63.4 +/- 10.2 years) with suspected coronary artery disease. All patients presented with atypical or typical chest pain and underwent CTCA and conventional coronary angiography (CA). For the CTCA scan (Sensation 64, Siemens, Germany), we administered an IV bolus of 100 ml of iodinated contrast material (Iomeprol 400 mgI/ml, Bracco, Italy). The CTCA and CA reports used to evaluate diagnostic accuracy adopted > or =50% and > or =70%, respectively, as thresholds for significant stenosis. RESULT: Eleven patients were excluded from the analysis because of the nondiagnostic quality of CTCA. The prevalence of disease demonstrated at CA was 63% (84/134). Sensitivity, specificity and positive and negative predictive values for CTCA on a per-segment, per-vessel, and per-patient basis were 75.6%, 85.1%, 97.6%; 86.9%, 81.8%, 58.0%; 48.2%, 68.1%, 79.6%; and 95.7%, 92.3%, 93.5%, respectively. Only two out of 134 eligible patients were false negative. Heart rate did not significantly influence diagnostic accuracy, whereas the absence or minimal presence of coronary calcification improved diagnostic accuracy. The positive and negative likelihood ratios at the per-patient level were 2.32 and 0.041, respectively. CONCLUSION: CTCA in the real clinical world shows a diagnostic performance lower than reported in previous validation studies. The excellent negative predictive value and negative likelihood ratio make CTCA a noninvasive gold standard for exclusion of significant coronary artery disease.

Side effects of anabolic androgenic steroids abuse.

Long-term side effects of high doses of anabolic androgenic steroids self-administration were evaluated in this study. Twenty male bodybuilders, voluntarily starting steroid self-administration, were followed every 6 months over 2 years. Physical examination, haematological, metabolic and endocrine variables, semen analysis, hepatic and prostate ultrasound and echocardiographic evaluations were performed. LH values (baseline 3.43 +/- 1.75) were suppressed at 18 (1.98 +/- 1.99) (p = 0.026) and 24 (2.43 +/- 2.17) (p = 0.026), and FSH (3.95 +/- 2.01) at 6 (3.01 +/- 2.16) (p = 0.031), 12 (2.45 +/- 2.54) (p = 0.029), 18 (2.02 +/- 2.29) (p = 0.032) and 24 (3.42 +/- 2.64) (p = 0.032) months and SHBG (34.11 +/- 10.88) values significantly lowered at 12 (24.81 +/- 12.49) (p < 0.05), 18 (21.28 +/- 11.15) (p < 0.01), 24 months (25.42 +/- 11.16) (p < 0.01). A significant decrease in spermatozoa count (p < 0.01), and fertility index (p = 0.01) occurred. HDL-cholesterol (baseline 56.94 +/- 13.54) was reduced at 18 (41.86 +/- 14.17) (p < 0.01) and 24 (43.82 +/- 18.67) (p < 0.05) months and Apo A-1 at 12 (p < 0.001), 18 (p = 0.05) and 24 (p = 0.05) months. The most important long-term adverse effects were lower fertility and the impairment of lipid profile associated with an increased cardiovascular risk.

Multislice computed tomography coronary angiography: clinical applications.

Cardiac and coronary computed tomography (CT) is becoming increasingly common in clinical practice. Even if there is no well-established evidence, this diagnostic modality is so strong and effective and, in skilled hand, it can be readily used in clinical practice. After learning its potential and the technical limits, this tool could be used for risk stratification as well as for revascularization evaluation. In this review, we will describe the results of present literature, clinical applications at present considered suitable to CT technology (i.e. 64-slice and dual-source scanners) and future applications and innovations.

Diagnostic accuracy of 64-slice CT in the assessment of coronary stents.

PURPOSE: The purpose of this study was to assess the diagnostic accuracy of 64-slice computed tomography (64-CT) coronary angiography in the detection of coronary in-stent restenosis. MATERIALS AND METHODS: Ninety-five patients (72 men and 23 women, mean age 58+/-8 years) with previous percutaneous coronary intervention with stenting and suspected restenosis underwent 64-CT (Sensation 64, Siemens). The mean time between stent deployment and 64-CT was 6.1+/-4.2 months. The scan parameters were: slices 32 x 2, individual detector width 0.6 mm, rotation time 0.33 s, feed 3.84 mm/rotation, 120 kV, 900 mAs. After the intravenous administration of iodinated contrast material (Iomeprol 400 mgI/ml, Iomeron, Bracco) and a bolus chaser (40 ml of saline), the scan was completed in <12 s. All coronary segments with a stent were assessed on 64-CT by two observers in consensus and judged as: patent, with intimal hyperplasia (lumen reduction of <50%), with in-stent restenosis (> or =50%), or with in-stent occlusion (100%). The consensus reading was compared with conventional coronary angiography. RESULTS: Four patients were excluded because of insufficient image quality. In the remaining 91, we assessed 102 stents (31 RCA; 10 LM; 54 LAD; 7 CX). In 14 (13.7%) stents, in-stent restenosis (n=8) or in-stent occlusion (n=6) was found. Intimal hyperplasia was detected in 11 (10.8%) stents. The sensitivity and negative predictive value of 64-CT for in-stent occlusion were 100% and 100%, respectively, whereas for all stenoses, >50% they were 92.9% and 98.7%, respectively. CONCLUSIONS: We found that 64-CT has a high diagnostic accuracy for the detection of in-stent restenosis in a selected patient population.

Disc coablation and epidural injection of steroids: a comparison of strategies in the treatment of mechanical spinal discogenic pain.

In this study two strategies in the treatment of Mechanical Spinal Discogenic Pain have been compared: Disc Coablation and Epidural Injection of Steroids. In 2003 50 patients treated with one or two epidural injections have been selected "ad random" and 50 patients treated with disc coablation. Comparison of the data indicated an improvement of average VAS when relaxed for both groups (p < 0.01), while after slight-moderate strain, this value was significant only after coablation (p < 0.001). Finally, average VAS was clearly lower (p < 0.01) after coablation as compared to epidural injections.

Ischaemic mitral valve regurgitation: a surgical approach.

UNLABELLED: The aim of this study IS to determine surgical results after surgical mitral valve repair in ischaemic mitral regurgitation. MATERIALS AND METHODS: Between January 1999 and June 2000, 64 patients (5.1% of overall patients) underwent myocardial revascularization and mitral valve surgery. A Cosgrove-Edwards mitral annuloplasty ring was used in 59 cases (92.2%). Average patient age was 64.3 +/- 12.4 years (38 males, 21 females). Average degree of mitral regurgitation was 2.8 +/- 0.6. Average NYHA class was 3.5 +/- 0.5. Average ejection fraction (EF) was 40 +/- 12.5 percent. RESULTS: Post-operative 30-day mortality was 3.4% (2 patients). The follow-up was complete for 95 percent (mean 20.4 +/- 4.8 months for patients) and data showed an improvement of NYHA class (mean value 1.8 +/- 0.2) (p = 0.01) and ejection fraction (mean value 51.7 +/- 10.2) (p = 0.05) with residual mitral regurgitation value of 0.6 +/- 0.7. CONCLUSIONS: Mitral valve repair in coronary artery disease improves left ventricular function, quality of life and survival rate with low operative risk. Perioperative transesophageal echocardiography has a central role in surgical decision making.

[Total arterial myocardial revascularization: surgical technique and mid-term results]. / La rivascolarizzazione miocardica arteriosa totale: tecnica chirurgica e risultati a medio termine.

The purpose of this study is to evaluate perioperative and mid-term results of total arterial coronary revascularization in our experience and to establish its safety. One-hundred and ninety-one patients underwent total arterial coronary revascularization at our Institution from February 1997 to August 2000. The mean age was 60.1 years. Of the patients, 45% had three coronary vessels disease, 12% a left main coronary artery disease and 2.6% of them were classified urgent. Mean ejection fraction was 59.6%. Three hundred and thirty-four comprehensive anastomoses were performed; mean grafts per patient was 1.8. A Y or T graft with the left internal thoracic artery was used in 21 patients. The in-hospital mortality rate was 1% (2 patients). Complications included low cardiac output syndrome in 2.8% of patients, acute myocardial infarction in 0.9% and acute renal insufficiency in 3.1%. Intraaortic balloon pump was used in 1.8% of patients. At a mean follow-up of 899 days the first 81 patients contacted are all free of angina but two (one experienced an acute myocardial infarction and another one died for a pulmonary neoplasia). We conclude that total arterial coronary revascularization is a safe surgical technique, providing excellent perioperative and mid-term results.

[Combined cardiac surgery and aneurysm of subrenal abdominal aorta]. / Chirurgia cardiaca e contemporanea resezione di aneurisma dell'aorta addominale sottorenale.

The authors explain their experience about the combined correction of cardiac pathology and infrarental aortic aneurysm repair. Seven patients of mean age of 63 years underwent simultaneous myocardial revascularization (5 cases) or aortic valve replacement (2 cases) and abdominal aortic aneurysm repair with bifurcated vascular prosthesis (6 cases) and tubular prosthesis (1 case) between 1987 and 1995. Cardiac operation was performed first with a mean number of 2.4 coronary artery by-pass grafts, with a mean by-pass time of 51 min, and a mean abdominal aortic cross-clamp time of 46 min. The mean total operating time was 231 min. All patients were managed postoperatively in the cardiac intensive care unit with a mean duration of 2.5 days and were transfused with a mean of 5 units of donor blood. The mean postoperative hospitalization was 9 days. One patient died for complication of postoperative myocardial infarction. The authors conclude that combined cardiac operation and abdominal aortic aneurysm repair is feasible in carefully selected patients.

[Low-flow anesthesia: isoflurane increment kinetics as a function of the rotatory circuit volume]. / Narcosi a "bassi flussi": cinetica di incremento dell'isoflurano in funzione del volume del circuito rotatorio.

OBJECTIVE: Study of the increment of isoflurane volume concentration in two rotatory circuits having different capacity during low flow narcosis. DESIGN: Descriptive comparison of different halogenate concentration in circuits connected to two patient groups and evaluation of the significance of the observed differences. SETTING: Surgery theatres of a district Public Hospital. PATIENTS: 16 female patients included in the same age, weight and body surface group, showing neither obstructive nor restrictive lung diseases. According to the surgical treatment used (abdominal or major gynecological surgery) the patients were then divided into two groups of 8 each. MEASUREMENTS AND MAIN RESULTS: After opening the halogenate nebulizer, dry measurement of the isoflurane concentration detected for 30 minutes in the inspiratory and expiratory circuit segment by means of monitors at pre-determined intervals, before abdominal or major gynecological surgery. Simultaneous measurement of isoflurane uptake by means of indirect methods (heart frequency, average arterial pressure, use of muscle relaxing agents). The analysis of the measured values showed higher isoflurane concentrations and a faster percent increase in the small circuit than in the big one (resp. 0.9% vs 0.71% in the inspiratory segment and 0.59% vs 0.4% in the expiratory one, with p < 0.005 and I.C. = 99.00%). CONCLUSIONS: This study demonstrates how the different kinetics of the isoflurane increment in the rotatory circuit is mainly related to the circuit volume. To eliminate the problems due to the "low compliance" of the small circuit (collection of toxic gases) and to the "high compliance" of the big circuit rotatory (awareness), circuits with varying volume might be introduced.