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Background and Purpose: The aim of our study was to elaborate a suitable model on bladder late toxicity in prostate cancer (PC) patients treated by radiotherapy with volumetric technique., Materials and Methods: PC patients treated between September 2010 and April 2017 were included in the analysis. An observational study was performed collecting late toxicity data of any grade, according to RTOG and CTCAE 4.03 scales, cumulative dose volumes histograms were exported for each patient. Vdose, the value of dose to a specific volume of organ at risk (OAR), impact was analyzed through the Mann-Whitney rank-sum test. Logistic regression was used as the final model. The model performance was estimated by taking 1000 samples with replacement from the original dataset and calculating the AUC average. In addition, the calibration plot (Hosmer-Lemeshow goodness-of-fit test) was used to evaluate the performance of internal validation. RStudio Software version 3.3.1 and an in house developed software package "Moddicom" were used., Results: Data from 175 patients were collected. The median follow-up was 39 months (min-max 3.00-113.00). We performed Mann-Whitney rank-sum test with continuity correction in the subset of patients with late bladder toxicity grade ≥ 2: a statistically significant p -value with a Vdose of 51.43 Gy by applying a logistic regression model (coefficient 4.3, p value 0.025) for the prediction of the development of late G ≥ 2 GU toxicity was observed. The performance for the model's internal validation was evaluated, with an AUC equal to 0.626. Accuracy was estimated through the elaboration of a calibration plot., Conclusions: Our preliminary results could help to optimize treatment planning procedures and customize treatments.

The management of individual patients requiring anthracyclines remains challenging because uncertainty persists on predictors of cardiotoxicity. We aimed to perform a systematic review and meta-analysis on incidence and predictors of anthracycline chemotherapy in patients with cancer. Databases were searched for pertinent studies. Meta-analytic pooling with random-effects methods was performed for incidence estimates, while relying on descriptive statistics for prevalence and strength of association of predictors. From 16,054 retrieved citations, 18 studies reporting on 49,017 patients with cancer were included, with 22,815 treated with anthracyclines. After a median follow-up of 9 years, clinically overt cardiotoxicity occurred in 6% (95% confidence interval 3% to 9%), whereas subclinical cardiotoxicity developed in 18% (95% confidence interval 12% to 24%). Appraisal of independent risk factors of cardiotoxicity showed that cumulative anthracycline dose was most consistently reported as an accurate and robust predictor of cardiotoxicity, with an acceptable prognostic role also for chest radiotherapy, African-American ethnicity, very young or very old age, diabetes, hypertension, very high or very low body weight, or severe co-morbidities. In conclusion, despite ongoing refinements in chemotherapy regimens, anthracyclines still pose a significant risk of cardiotoxicity, especially in those requiring a high cumulative dose or chest radiotherapy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Anthracyclines are established cardiotoxic agents; however, the exact extent and time course of such cardiotoxicity has not been appraised in detail. We aimed to exploit serial measurements of standard and tissue Doppler imaging (TDI) echocardiographic parameters collected in a prospective clinical trial to clarify the outlook of cardiac function during and long after anthracycline chemotherapy. Women enrolled in a randomized trial focusing on liposomal doxorubicin-based chemotherapy for breast cancer and providing ≥4 separate echocardiographic assessments were included. Repeat-measure nonparametric analyses were used to appraise changes over time in the standard and tissue Doppler imaging echocardiographic parameters. A total of 39 patients with serial imaging evaluations were enrolled. Significant temporal changes were found for the left ventricular ejection fraction and diastolic parameters, despite different temporal trends. Specifically, the left ventricular ejection fraction exhibited a V-shaped trend, decreasing initially from 63% to 61% but then recovering to 64% (p <0.001), with a similar trend in the TDI E/Em ratio (p = 0.011). In contrast, persistent impairments typical of an L-shaped trend were found for the E wave (p = 0.006), TDI lateral Em wave (p = 0.001), and TDI septal Em wave (p = 0.001). In conclusion, subclinical temporal changes in the standard and TDI echocardiographic parameters after anthracycline chemotherapy showed a distinctive pattern of transient impairment followed by full recovery of the left ventricular ejection fraction versus a persistent impairment of the diastolic parameters, which must be taken into account in the everyday treatment of such patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: The antineoplastic efficacy of anthracyclines is limited by their cardiac toxicity. In this study, we evaluated the toxicity of doxorubicin, non-pegylated liposomal-delivered doxorubicin, and epirubicin in HL-1 adult cardiomyocytes in culture as well as in the mouse in vivo., Methods: The cardiomyocytes were incubated with the three anthracyclines (1 µM) to assess reactive oxygen generation, DNA damage and apoptotic cell death. CF-1 mice (10/group) received doxorubicin, epirubicin or non-pegylated liposomal-doxorubicin (10 mg/kg) and cardiac function was monitored by Doppler echocardiography to measure left ventricular ejection fraction (LVEF), heart rate (HR) and cardiac output (CO) both prior to and 10 days after drug treatment., Results: In HL-1 cells, non-pegylated liposomal-doxorubicin generated significantly less reactive oxygen species (ROS), as well as less DNA damage and apoptosis activation when compared with doxorubicin and epirubicin. Cultured breast tumor cells showed similar sensitivity to the three anthracyclines. In the healthy mouse, non-pegylated liposomal doxorubicin showed a minimal and non-significant decrease in LVEF with no change in HR or CO, compared to doxorubicin and epirubicin., Conclusion: This study provides evidence for reduced cardiac toxicity of non-pegylated-liposomal doxorubicin characterized by attenuation of ROS generation, DNA damage and apoptosis in comparison to epirubicin and doxorubicin.

Background: Cardiomyopathy following anthracycline chemotherapy may have ominous clinical implications in cancer patients treated with this effective yet potentially toxic therapy. Early detection at subclinical stage is pivotal to minimize the risk of overt cardiotoxicity. Liposomal anthracyclines have the potential for more selective uptake by cancer cells and reduced cardiac toxicity., Objective: We designed a single-center randomized clinical trial, the Liposomal doxorubicin-Investigational chemotherapy-Tissue Doppler imaging Evaluation (LITE) pilot study to compare the safety of liposomal doxorubicin vs standard epirubicin in terms of clinical and subclinical cardiotoxicity., Methods: Whereas diagnostic and prognostic instruments effective at early recognition of cardiomyopathy are lacking, promising data have been reported for tissue Doppler imaging (TDI) echocardiography. The study will enroll 80 patients with breast cancer and indication to anthracycline chemotherapy, randomizing them in a 1:1 ratio to liposomal doxorubicin or standard epirubicin. The primary end-point will be the comparison of changes from baseline to 12-month follow-up of left ventricular TDI systolic function parameters, and the co-primary end-point will be based instead on changes in TDI diastolic function parameters. Among secondary end-points, we will adjudicate changes in standard 2-dimensional echocardiography parameters, including ejection fraction, peak values of biochemical markers of cardiac damage and heart failure, ie cardiac troponin T and BNP, overall survival, functional class, freedom from cancer recurrence, and adverse effects of chemotherapy., Conclusions: Results of the LITE pilot study should provide important clinical and mechanistic insights on the promising role of liposomal anthracyclines in patients with breast cancer and indication to anthracycline chemotherapy (ClinicalTrials.gov identifier NCT00531973).

Aim: Anthracycline (ANT) chemotherapy for breast cancer, while associated with high response rates, is fraught by risks of irreversible cardiotoxicity. Unfortunately means to detect such cardiotoxicity early on and at a sublinical stage are lacking. We evaluated the role of systolic tissue Doppler imaging (TDI) in appraising postchemotherapy left ventricular (LV) remodelling., Methods: Patients undergoing ANT-chemotherapy for breast cancer were enrolled, and underwent baseline and >6-months echocardiography (standard and TDI). According to the pattern of LV-TDI systolic remodelling from baseline to follow-up, patients were stratified in: group 1 (no LV-TDI worsening), group 2 (minor LV-TDI worsening), and group 3 (major LV-TDI worsening). Fifty-six patients were included (follow-up 9+/-6 months)., Results: At baseline, no patient had abnormal LV ejection fraction (LVEF), LV-TDI systolic dysfunction or New York Heart Association (NYHA) >1. Follow-up overall analysis showed significant deterioration in LVEF, end-diastolic diameter (EDD) end-systolic diameter (ESD), and TDI-systolic parameters (all P<0.05). Specifically, 29 (51.8%) patients showed no adverse LV-TDI systolic remodelling, while 17 (30.4%) were in group 2, and 10 (17.9%) in group 3. All groups shared similar conditions at baseline. Patients with adverse LV-TDI remodelling had significant increases in EDD and ESD, as well as a significantly decreased LVEF (all P<0.05). No patient in group 1 had abnormal LVEF at follow-up, while 1 patient in group 2 and 2 patients in group 3 had abnormal LVEF (P<0.05)., Conclusion: Subclinical systolic dysfunction occurs in almost 50% of patients early after chemotherapy for breast cancer, with a more adverse by LV-TDI remodelling implying a more pronounced deterioration of standard echocardiographic parameters.

Lymphedema represents one of the major problem of morbidity in breast cancer therapy. Approximately 15-30% of patients show more or less severe lymphedema of the arm, following cancer therapy. Main pathogenetic mechanisms, risk factors, main grading criteria and scales as LENT-SOMA, CTCv2, CTCAE v3 are presented. A close correlation has been documented between the extent of axillary dissection and the association with radiotherapy in determining an increased risk of lymphedema. Details of surgery and radiotherapy are relevant in the definition of the risk of edema of the arm. Because the axillary area does not correspond to an organ, evaluable parameters as V20 and Dmean available for other organs are not applicable. There is some evidence of a correlation between the irradiation volume and the development of lymphedema. Data of the impact of the dose and its fractionation on the development of lymphedema are contrasting. The monitoring system of late toxicity used by the authors is presented.

Standard radiotherapy in breast cancer is performed at the dose of 1.8-2 Gy daily 5 fractions a week for a total dose between 45 and 60 Gy. However research is addressed to different fractionations. For total time reduction, the interest was focused on conventional brachytherapy which radiobiologically represents "continuous" accelerated hyperfractionation, as well as on conventional external beam radiotherapy with accelerated hyperfractionation. A phase I study was conducted to define and validate a radiotherapy schedule with non conventional fractionation. Nine patients with metastatic breast cancer were enrolled in the study. None of them had undergone breast surgery or lymph node dissection. They were sequentially divided into three different, progressively increasing dose levels administered with double daily fractionation. Each schedule of accelerated fractionation (AF) included the administration of 1.8 Gy in two daily fractions, at least six hours apart for 10, 11 and 12 days and a total dose of 36, 39.6 and 43.2 Gy, respectively. Results of dose escalation, acute toxicity and mathematical calculation of radiobiological equivalence led to consider the dose of 36 Gy in 20 fractions during 10 days the most suitable for cost/benefit ratio within a non conventional fractionation.

Objective: To our knowledge, Doppler data for the inferior mesenteric artery are currently restricted to healthy patients. The present study was conducted to evaluate changes in inferior mesenteric artery flow in patients with inflammatory bowel disease., Subjects and Methods: Doppler sonography of the inferior mesenteric artery was prospectively performed in 24 patients with Crohn's disease (active, n = 15; inactive, n = 9), in 22 patients with ulcerative colitis (active, n = 14; inactive, n = 8), and in 40 healthy controls. Disease activity was determined with clinical and laboratory indicators (medical history, physical examination, laboratory data, and endoscopy with histology). Flow velocity, pulsatility index, and estimated flow volume were measured in all patients and compared with the corresponding values for control subjects. Hemodynamic parameters were then correlated with location of disease (small bowel and right and proximal transverse colon versus distal transverse and left colon) and disease activity or inactivity., Results: Among patients with active disease, inferior mesenteric artery flow was significantly greater in those with left colon involvement (group 1, 20 patients) than in patients with involvement of the small bowel or right colon (group 2, nine patients) and in control subjects. Median flow values for group 1 were peak systolic velocity, 1.96+/-0.57 m/sec; mean velocity, 0.63+/-0.25 m/sec; minimum velocity, 0.17+/-0.20 m/sec; pulsatility index, 3.07+/-1.24; and estimated flow volume, 0.40+/-0.17 l/min. Median flow values for group 2 were peak systolic velocity, 1.27+/-0.56 m/sec; mean velocity, 0.29+/-0.14 m/sec; minimum velocity, 0.06+/-0.10 m/sec; pulsatility index, 4.71+/-0.98; and estimated flow volume, 0.14+/-0.11 l/min. Median flow values for control subjects were peak systolic velocity, 1.41+/-0.48 m/sec; mean velocity, 0.43+/-0.19 m/sec; minimum velocity, 0.10+/-0.16 m/sec; pulsatility index, 3.49+/-0.49; and estimated flow volume, 0.13+/-0.06 l/min. Compared with control subjects, patients with acute disease involving the left colon (group 1) presented increases in flow velocity (systolic velocity, p < .001; minimum velocity, p = .01; mean velocity, p < .001) and estimated flow volume (p < .001) and a decreased pulsatility index (p = .01). A significant increase in inferior mesenteric artery flow was also found when group 1 patients were compared with those of group 2 (active disease affecting the small bowel and right colon) and group 3 (13 patients with quiescent disease of the left colon)., Conclusion: In this preliminary study, active inflammation of the left colon in patients with Crohn's disease or with ulcerative colitis was associated with a substantial increase in inferior mesenteric artery flow that could be seen on Doppler sonography.

The radical change in the health care service now going on for some years requires the commitment of medical specialists, as well as the acquisition of an adequate knowledge of the economic implications associated to the therapeutic choice. Among primary objectives of health care management in the field of breast cancer, the best cost-effective strategy and the rationalization and standardization of diagnostic and therapeutic approaches, should be identified. Problems related to breast cancer are examined for effective, efficient and economic optimization.

The role of radiotherapy in breast cancer is examined, based on a review of literature. Its impact on survival is discussed in the framework of a multidisciplinary treatment of the disease.

New challenging dosimetric approaches, such as narrow beams and 3D algorithms, are being used in radiotherapy. In this paper two quality control (QC) procedures are reported. The first one concerns the QC of the dosimetry of small x-ray beams, generally carried out by using silicon detectors. The comparison of dose values obtained by a silicon diode, a diamond detector, and radiochromic films shows that for x-ray beams of high energy, the silicon diode can give an overestimation of the output factors in phantom, up to 4%. This is due to the higher than unit density silicon diode and the surrounding envelope that restore the lateral electron equilibrium. About the 3D algorithms for breast treatment planning, a quality control test has been adopted to verify the accuracy of the computed dosimetry when "loss of scatter" occurs. The results show a sensible agreement (within 1.5%) between computed and experimental data.

Bladder cancer is frequent in Western countries and predominantly affects males (ratio: 3:1). In 15-25% of cases there is muscular wall invasion. Treatment of > T1 tumors is radical cystectomy with or without preoperative radiotherapy. In T2 there is 60% survival at 5 years, 40% in T3. Exclusive radiotherapy used to prevent radical cystectomy has lower survival rates in T2 (30-40% at 5 years) as well as in T3 (20% at 5 years). Recently, concomitant radiotherapy and chemotherapy has been introduced again to prevent demolitive surgery. Results are similar or slightly superior than those of surgery alone. In our experience with radiotherapy 180 cGy daily for a total dose of 64 Gy in combination with fluorouracil in locally advanced tumors 40% bladder preservation was achieved.

Aim of this study was to evaluate the feasibility, therapeutic effectiveness and toxicity of a non conventional radiation therapy (180 cGy twice a day for a total dose of 36 Gy in 2 weeks in the treatment of breast cancer inoperable with conservative surgery as first choice. Ten patients were studied. Results were as follows: complete response: 20%, partial response: 70%; no change: 10%. Acute toxicity was negligible and late toxicity, after a mean 46-month follow-up, was practically absent; the cosmetic result was definitely good. The radiobiology and kinetic features of breast cancer indicate that the potential of accelerated treatment should be further explored, this fractionation being suitable for optimal combined modality treatment with preoperative chemotherapy.

The calculated absorbed dose values to the reference point of the breast tangential irradiation, obtained by 2-dimensional (2D) Treatment Planning Systems (TPS), were compared with the measured absorbed dose values obtained with a ionization chamber in an anthropomorphic phantom treated with two opposed photon beams of 60Co, 6 MV and 10 MV. This comparison was aimed at assessing the 2D algorithm dose overestimation due to the effect of missing tissue in the irradiated field. The ratio between the computed dose, Dc, and the measured dose, Dm, reached 1.08 for 60Co beams and 1.04 for X-ray beams of linacs. The Clarkson method gives an adequate correction factor for the calculated absorbed dose value in the reference point. The portal films of some patients were studied to estimate the correction factor for the treatment time or monitor units evaluated by TPS using tomographic breast central plane. The values of the correction factors reached 1.10 for 60Co photon beams and 1.04 for X-ray beams. The measurements were carried out with TLDs positioned in the central plane of the breast, covered by a special bolus, of a second anthropomorphic phantom. The dose homogeneity as well as the accuracy of the relative computed dose values in the breast phantom irradiated with 10 MV X-ray beams were assessed.

Coenzyme Q10 (CoQ10), a quinone located in cellular membranes, is a compound with mitochondrial bioenergetic functions whose antioxidant activity has recently been defined. CoQ10 content in colorectal neoplasms is significantly higher than in normal colorectal mucosa. While older patients (aged over 70 years) have also a significantly higher CoQ10 content, not observed in younger patients (aged under 70 years), the normal mucosa, instead; shows constant CoQ10 levels in both groups. For the same local stage (T), an increase in lymph node involvement (N) was observed in older patients as compared to younger ones, but not in distant metastases (M) with the same 5-year survival. These results justify the same therapeutic approach for patients older or younger than 70 years.

Radiation therapy represents an extensively experimented treatment modality for head and neck tumors. Recent studies have documented a close dependence of clinical results, especially in terms of local control and toxicity, on the radiation therapy quality. Thus the effort to improve the results of conventional radiotherapy has been achieved with the identification of new therapeutic modalities (non conventional fractionation, conformal therapy, fast neutron radiotherapy, concomitant or neoadiuvant chemotherapy) as well as with constant optimization of the accuracy of used procedures. Among them the following should be mentioned: 1) the systematic use of immobilization systems which enable a significant reduction in positioning errors; 2) checks before and during treatment by portal imaging which enable to identify and correct a relevant percentage of inaccuracies; 3) "in vivo" dosimetry which enables an overall assessment of treatment accuracy. The general evolution of the radiobiological knowledge occurred in recent years has introduced into radiotherapy of head and neck tumors new schemes of fractionation and new modalities of combination with other therapeutic procedures. Furthermore, while the widespread use of complex irradiation procedures calls for the urgent need of quality assurance of radiation treatments, this is by all means a mandatory requirement even in the most conventional clinical practice.

In order to compare the capacities of quantitative ultrasonography and dual energy X-ray absorptiometry to measure bone mineral density (BMD) in postmenopausal women, 45 postmenopausal patients were studied. They were divided into two groups on the basis of the results of absorptiometry: Group A (20 patients) had BMD values within normal limits, and Group B (25 patients) had BMD values lower than 1 standard deviation (SD) of the average for an age and sex matched population. Ultrasonography of the non-dominant heel was carried out on both groups to determine broadband ultrasound attenuation (BUA), speed of sound (SOS) and bone velocity (BV). A negative correlation between age and BMD, BV, SOS, and BUA was observed in all subjects. A positive correlation between BMD and BV and between BMD and SOS was found. In Group A, age correlated negatively with BMD, BUA, SOS and BV, and BMD correlated positively with BV. In Group B, age correlated negatively with BMD, and BMD correlated positively with BV and SOS. BV values were significantly elevated in Group B. The study evidenced a relationship between ultrasonography and absorptiometry in determining bone density in postmenopausal women. As ultrasonography and absorptiometry provided comparable information on bone density, we point out that ultrasonography can be used as a simple and sensitive indicator for postmenopausal osteoporosis.

The conventional and Doppler US assessment of the inferior mesenteric artery has not been reported in the literature to date. In the present study, the feasibility of Doppler US of the inferior mesenteric artery was prospectively investigated in 112 consecutive nonselected patients; the corresponding morphological features (size and vessel course) and Doppler flowmetry (peak systolic, peak diastolic and mean velocities; pulsatility index) were defined. In 32 patients (29%) neither conventional nor color-Doppler nor duplex imaging was possible. Of the extant 80 patients, in 65 (81%) all the three methods allowed the correct assessment of the inferior mesenteric artery; in 15 patients (19%) the results were suboptimal (poor US visualization, or inadequate Doppler flowmetry). In 33/80 patients, arterial blood flow was quantitatively assessed in 1/min. As for the patients who underwent further diagnostic procedures--e.g., CT and angiography--a close correlation was demonstrated between the morphological and functional data obtained by Doppler US and the corresponding CT and angiographic features. The possibility of analyzing the inferior mesenteric artery with conventional and Doppler US, besides the celiac trunk and the superior mesenteric artery, should allow splanchnic circulation to be more completely assessed, thanks to information about normal hemodynamics (after a meal or in response to pharmacological treatments) as well as about the diseases known to affect intestinal perfusion--e.g., mesenteric ischemia.