Offshore telemedicine emergency service: a 1-year experience

Journal of Public Health - Offshore wind energy is a fast growing market. Accordingly, a correspondingly large number of employees are working at the wind farms. Owing to the harsh operating...     

Detection of TP53 mutation, loss of heterozygosity and DNA content in fine-needle aspirates of breast carcinoma.

Recent preclinical and clinical data suggest that TP53 status and TP53 mutations may be important in determining tumour aggressiveness and therapy response. In this study we investigate the feasibility of a structural and quantitative analysis of TP53 on fine-needle aspiration (FNA) material obtained from 31 consecutive female patients with breast carcinoma, enrolled in a primary chemotherapy protocol. Tumours were screened for p53 protein overexpression and TP53 mutations (exons 5-8) using immunocytochemistry, polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing analyses, and finally using fluorescence in situ hybridization (FISH) analysis. Positive nuclear staining was identified in six cases whereas mutations were detected in nine. Although the immunoreactive pattern fitted fully with the characterized TP53 mutation type, the considerable number of null p53 mutations (i.e. four) coupled with the lack of information regarding the localization of TP53 mutations make immunocytochemistry an inadequate indicator of TP53 function deregulation. Combining molecular and FISH analyses, we detected three cases with TP53 deletion and one case with deletion and mutation. Finally, DNA static-image analysis performed on 29 cases showed aneuploidy in 26 cases, which included all TP53-mutated cases. The present results show that FNA may assist clinical decisions by allowing the evaluation of a variety of biological parameters relevant for prognosis and treatment planning.     

Unilateral aneuploid dedifferentiated acinic cell carcinoma associated with bilateral-low grade diploid acinic cell carcinoma of the parotid gland

A dedifferentiated acinic cell carcinoma (AciCC) of the right parotid gland with lymph node metastases occurred in a 36-year-old woman. The tumour was associated with a bilateral well-differentiated AciCC. The two components of this tumour had different (high and low) proliferative activity measured by Mib-1 and different (aneuploid and diploid) DNA content. Despite the presence of a high-grade component, TP53 mutations, microsatellite instability (MSI) and/or loss of heterozygosity (LOH) at the p53 locus were not detected. Although the follow-up of the patient is very short, the aggressiveness of the tumour is shown by a recurrence in the right parotid within 4 months and by the rapid development of regional metastases.     

1D dynamic beam modulation: methods to counteract inertia effects

Dynamic modulation can be affected by inaccuracies when the required acceleration is larger than the highest allowed by the mechanical characteristics of the whole apparatus. In this study, inertia effects have been investigated with regard to the single absorber 1D modulation, analysing primarily how the acceleration performed by the modulating system affects the realization of 'single absorber' fluence profiles and the type of correction which could be devised. The observed percentage deviations from desired modulation at the lowest fluence coordinate of single minimum fluence profiles, when no correction is applied, were almost negligible for 'easy' modulations of the incident fluence (i.e. slow gradients); deviations became increasingly relevant as the moving absorber executed steeper gradients (a 17.6% higher dose being delivered in the minimum position when a 0.2 modulation is required). By applying the proposed corrections, the single absorber performances were improved to a satisfactory level, with a maximum deviation from desired modulation in the minima within 1.6%.     

Inverse and forward optimization of one- and two-dimensional intensity-modulated radiation therapy-based treatment of concave-shaped planning target volumes: the case of prostate cancer.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) was suggested as a suitable technique to protect the rectal wall, while maintaining a satisfactory planning target volume (PTV) irradiation in the case of high-dose radiotherapy of prostate cancer. However, up to now, few investigations tried to estimate the expected benefit with respect to conventional three-dimensional (3D) conformal radiotherapy (CRT). PURPOSE: Estimating the expected clinical gain coming from both 1D and 2D IMRT against 3DCRT, in the case of prostate cancer by mean of radiobiological models. In order to enhance the impact of IMRT, the case of concave-shaped PTV including prostate and seminal vesicles (P+SV) was considered. MATERIALS AND METHODS: Five patients with concave-shaped PTV including P+SV were selected. Two different sets of constraints were applied during planning: in the first one a quite large inhomogeneity of the dose distribution within the PTV was accepted (set (a)); in the other set (set (b)) a greater homogeneity was required. Tumor control probability (TCP) and normal tissue control probability (NTCP) indices were calculated through the Webb-Nahum and the Lyman-Kutcher models, respectively. Considering a dose interval from 64.8 to 100.8 Gy, the value giving a 5% NTCP for the rectum was found (D(NTCP(rectum)=5%)) using two different methods, and the corresponding TCP(NTCP(rectum)=5%) and NTCP(NTCP(rectum)=5%) for the other critical structures were derived. With the first method, the inverse optimization of the plans was performed just at a fixed 75.6 Gy ICRU dose; with the second method (applied to 2/5 patients) inverse treatment plannings were re-optimized at many dose levels (from 64.8 to 108 Gy with 3.6 Gy intervals). In this case, three different values of alpha/beta (10, 3, 1.5)were used for TCP calculation. The 3DCRT plan consisted of a 3-fields technique; in the IMRT plans, five equi-spaced beams were applied. The Helios Inverse Planning software from Varian was used for both the 2D IMRT and the 1D IMRT inverse optimization, the last one being performed fixing only one available pair of leaves for modulation. A previously proposed forward 1D IMRT 'class solution' technique was also considered, keeping the same irradiation geometry of the inversely optimized IMRT techniques.RESULTS: With the first method, the average gains in TCP(NTCP(rectum)=5%) of the 2D IMRT technique, with respect 3DCRT, were 10.3 and 7.8%, depending on the choice of the DVHs constraints during the inverse optimization procedure (set (a) and set (b), respectively). The average gain (DeltaTCP(NTCP(rectum)=5%)) coming from the inverse 1D IMRT optimization was 5.0%, when fixing the set (b) DVHs constraints. Concerning the forward 1D IMRT optimization, the average gain in TCP(NTCP(rectum)=5%) was 4.5%. The gain was found to be correlated with the degree of overlapping between rectum and PTV. When comparing 2D IMRT and 1D IMRT, in the case of the more realistic set (b) constraints, DeltaTCP(NTCP(rectum)=5%) was always less than 3%, excepting one patient with a very large overlap region. Basing our choice on this result, the second method was applied to this patient and one of the remaining. Through the inverse re-optimization of the treatment plans at each dose level, the gain in TCP(NTCP(rectum)=5%) of the inverse 2D technique was significantly higher than the ones obtained by applying the first method (concerning the two patients: +6.1% and +2.4%), while no significant benefit was found for inverse 1D. The impact of changing the alpha/beta ratio was less evident in the patient with the lower gain in TCP(NTCP(rectum)=5%). CONCLUSIONS: The expected benefit due to IMRT with respect to 3DCRT seems to be relevant when the overlap between PTV and rectum is high. Moreover, the difference between the inverse 2D and the simpler inverse or forward 1D IMRT techniques resulted in being relatively modest, with the exception of one patient, having a very large overlap between rectum and PTV. Optimizing the inverse planning at each dose level to find TCP(NTCP(rectum)=5%)e level to find TCP(NTCP(rectum)=5%) can improve the performances of inverse 2D IMRT, against a significant increase of the time for planning. These results suggest the importance of selecting the patients that could have significant benefit from the application of IMRT.     

Conformal irradiation of concave-shaped PTVs in the treatment of prostate cancer by simple 1D intensity-modulated beams.

BACKGROUND: In the case of concave-shaped PTVs including prostate (P) and seminal vesicles (SV), intensity-modulated radiation therapy (IMRT) should improve the therapeutic ratio of the treatment of prostate cancer. PURPOSE: Comparing IMRT by simple 1D modulations with conventional 3D conformal therapy (i.e. non-IMRT) in the treatment of concave-shaped PTVs including P+SV. MATERIALS AND METHODS: For five patients having a concave-shaped PTV (P+SV) previously treated at our Institute with conformal radiotherapy, conventional 3- and 4-fields conformal plans were compared with IMRT plans in terms of biological indices. IMRT plans were generated by using five equi-spaced beams with a partial shielding of the rectum obtainable with our single-absorber modulation technique (Fiorino C, Lev A, Fusca M, Cattaneo GM, Rudello F, Calandrino R. Dynamic beam modulation by using a single dynamic absorber. Phys. Med. Biol. 1995;40:221-240). The modulation was one-dimensional and the shape of the beams was at single minimum in correspondence with the 'core' of the rectum; the beam intensity in the minimum was set equal to 20 or 40% of the open beam intensity. All plans were simulated on the CADPLAN TPS using a pencil-beam based algorithm (with 18 MV X-rays). Tumour control probability (TCP) and normal tissue complication probabilities (NTCPs) (for rectum, bladder and femoral head) were calculated for all situations when varying the isocentre dose from 60 to 90 Gy. Dose distributions were corrected taking dose fractionation into account through the linear-quadratic model; for the TCP/NTCP estimations the Webb-Nahum and the Lyman-Kutcher models were respectively applied. Three different scores were considered: (a) increase of TCP while keeping rectum NTCP equal to 5% (TCP(5%)); (b) increase of the uncomplicated tumour control probability (P+); (c) increase of the biological-based scoring function (S+), developed by Mohan et al. (Mohan R, Mageras GS, Baldwin B, Clinically relevant optimization of 3D conformal treatments. Med. Phys. 1992;19:933-944). The impact of the uncertainty in the knowledge of the parameters of the biological models was investigated for TCP(5%). RESULTS: (a) The average gain in TCP(5%) when considering IMRT against non-IMRT conformal plans was 7.3% (range 5.0-13.5%); (b) the average increase of P+ was 3.4% (range: 1. 0-8.5%); and (c) the average increase of S+ was 5.4% (range 2.9-12. 4%). The largest gain was found for one patient (patient 5) showing a significantly larger overlapping between PTV and rectum. CONCLUSIONS: Simple 1D-IMRT may clearly improve the therapeutic ratio in the treatment of concave-shaped PTVs including P and SV. In the range of clinically suitable values, the impact of the uncertainty of the parameters n and sigma(alpha) does not significantly alter the main results concerning the gain in TCP(5%). The reported gain in terms of P+ and S+ should be considered with great caution because of the intrinsic uncertainties of the model's parameters and, for bladder, because the 'true' DVH (considering variations of the shape and dimension due to variable filling) may be very different from the DVH calculated on a single CT scan. Further investigations should consider inversely-optimised 1D and 2D-IMRT plan in order to compare them in terms of cost-benefit.     

Quality assurance by systematic in vivo dosimetry: results on a large cohort of patients.

BACKGROUND: In vivo dosimetry is widely considered to be an important tool for quality assurance in external radiotherapy. Introduction: In this study we report on our experience over more than 4 years in systematic in vivo dosimetry with diodes. MATERIALS AND METHODS: From November '94 an in vivo entrance dosimetry check was performed for every new patient irradiated at one of our treatment units (Linac 6/100, 6 MV X-rays). Diodes were calibrated in terms of entrance dose; appropriate correction factors had been previously assessed (taking SSDs, field width, wedge, oblique incidence and blocking tray into account) and were individually applied to in vivo diode readings. The in vivo measured entrance dose was compared with the expected one, with a 5% action level; if a larger deviation was found, all treatment parameters were verified, and the in vivo dosimetry check was repeated. During the period November '94-May '99, 2824 measurements on 1433 patients were collected. RESULTS: Nine out of 1433 (0.63%) serious systematic errors (leading to a 5% or more on the delivered dose to the PTV) were detected by in vivo dosimetry; four out of nine would produce a 10% or more error if not detected. The rate of serious systematic errors detected by an independent check of treatment chart and MU calculation was found to be 1.5%, showing that less than 1/3 of the errors escapes this check. One hundred and twelve out of 1433 (7.8%) patients had more than one check: the rate of second checks was significantly higher for breast patients (31/250, 12.4%) against non-breast patients (81/1183, 6.8%, P=0.003). A number of patients demonstrated a persistent relatively large error even after two or more checks. For almost all patients the cause of the deviation was assessed; the most frequent cause was the difficulty in correctly positioning the patient and/or the diode. When analyzing the distribution of the deviations between measured and expected entrance doses (excluding first checks in the case of repetition of the in vivo dosimetry control) the mean deviation was 0.4% with a standard deviation equal to 3.0%. The rates of deviations larger than 5 and 7% were 9.9 and 2.6%, respectively. When considering the same data taking the average deviation in the case of opposed beams, the SD became 2.6% and the rates of deviations larger than 5 and 7%, respectively, 5.2 and 0.8%. When dividing the beams according to their orientation, significantly higher rates of large deviations (>5 and 7%) were found for oblique and posterior-anterior (PA) fields against lateral and anterior-posterior (AP) fields (P<0.05). Similarly, higher rates of large deviations were found for wedged fields against unwedged fields (P<0.03) and for blocked fields against unblocked fields (P<0.01). When dividing the data according to the anatomical district, accuracy was worse for breast (mean deviation 0.1%, 1 SD: 3.5%) and neck AP-PA fields (mean deviation 1%, 1 SD: 3,4%). Better accuracy was found for vertebrae (0.1%, 1 SD 2. 1%) and brain patients (-0.7%, 1 SD: 2.6%). During the considered period, in vivo dosimetry was also able to promptly detect a systematic error caused by a wrong resetting of the simulator height couch indicator, with a consequent error in the estimate of patient thickness of about 4 cm. CONCLUSIONS: In our experience, systematic in vivo dosimetry demonstrated to be a valid tool for quality assurance, both in detecting systematic errors which may escape the data transfer/MU calculation check and in giving an effective way of estimating the accuracy of treatment delivery.