Background
In selected patients with N0 rectal cancer, endoluminal loco-regional resection (ELRR) by transanal endoscopic microsurgery (TEM) may be an alternative treatment option to laparoscopic ...total mesorectal excision (LTME). Aim of this study is to evaluate the short- and medium-term quality of life (QoL) from a retrospective analysis of prospectively collected data in patients with iT2–iT3 N0-N+ rectal cancer, who underwent ELRR by TEM or LTME after neoadjuvant radio-chemotherapy (n-RCT).
Methods
Thirty patients with iT2–iT3 rectal cancer who underwent ELRR by TEM (
n
= 15) or LTME (
n
= 15) were enrolled in this study. The choice for one operation or the other was made on the basis of predefined criteria. QoL was evaluated by EORTC QLQ-C30 and QLQ-CR38 questionnaires at admission, after n-RCT and 1, 6, and 12 months after surgery.
Results
No statistically significant differences in QoL evaluation were observed between the two groups, both at admission and after n-RCT. At 1 month after surgery, significantly better results in the ELRR group were observed by QLQ-C30 in: Nausea/Vomiting (
p
= 0.05), Appetite Loss (
p
= 0.003), Constipation (
p
= 0.05), and by QLQ-CR38 in: Body Image (
p
= 0.05), Sexual Functioning (
p
= 0.03), Future Perspective (
p
= 0.05) and Weight Loss (
p
= 0.036). At 6 months after surgery, a statistically significant worse impact after LTME was observed by QLQ-C30 in: Global Health Status (
p
= 0.05), Emotional Functioning (
p
= 0.021), Dyspnea (
p
= 0.008), Insomnia (
p
= 0.012), Appetite Loss (
p
= 0.014) and by QLQ-CR38 in Body Image (
p
= 0.05) and Defecation Problems (
p
= 0.001). At 1 year, the two groups were homogenous as assessed by QLQ-C30, whereas the QLQ-CR38 still showed better results of ELRR versus LTME in Body Image (
p
= 0.006), Defecation Problems (
p
= 0.01), and Weight Loss (
p
= 0.005).
Conclusions
Based on the present series, in selected patients, earlier restoration of patients’ functions is observed after ELRR by TEM than after LTME.
The knowledge on bovine vaccines against respiratory viruses on bronchoalveolar fluid cells is scarce.
To compare the effects of a commercial intranasal (IN) and intramuscular (IM) vaccine against ...bovine respiratory disease (BRD) complex viruses on bronchoalveolar fluid cells of healthy heifers.
21 healthy heifers were assigned to three treatment groups: control (CO, N = 7), intranasally vaccinated (IN) (n = 7), and intramuscularly vaccinated (IM) (n = 7). The IN group received 1 mL of the commercial vaccine in each nostril once containing attenuated BoHV-1, bPIV-3, and BRSV. The IM group was vaccinated with two doses of 2 mL with an interval of 21 days of the commercial vaccine containing attenuated BoHV-1, bPIV-3, and BRSV plus inactivated BVDV. At day 0 (D0), before the first vaccine dose, and at D3, D7, and D21, after the last vaccine dose, airway bronchoscopy was performed to observe local irritation and collect bronchoalveolar lavage fluid (BALF). The bronchoalveolar count, cytological evaluation, bronchoalveolar cell oxidative metabolism, and total bronchoalveolar IgA and IgG were measured.
The IN vaccine increased neutrophil cellularity at D7 and D21 and total IgA at D3 in BALF. Total IgA in BALF also increased at D3 and oxidative metabolism of bronchoalveolar cells at D21 lowered compared to the CO group. Following IM vaccination there was no alteration of immunoglobulins or cell oxidative metabolism in BALF. Both vaccines reduced the number of alveolar macrophages.
Both vaccines induced bronchoalveolar inflammation during the establishment of the vaccine immunity, which was more expressive in the IN protocol.
The radiation used in hadrontherapy treatments interacts with the patient body producing secondary particles, either neutral or charged, that can be used for dose and Bragg peak monitoring and to ...provide a fast feedback on the treatment plans. Recent results obtained from the authors on simplified setups (mono-energetic primary beams interacting with homogeneous tissue-like target) have already indicated the correlation that exists between the flux of these secondaries coming from the target (e.g. protons and photons) and the position of the primary beam Bragg peak. In this paper, the measurements of charged particle fluxes produced by the interaction of a 220 MeV/u carbon ion beam at GSI, Darmstadt, with a polymethyl methacrylate target are reported. The emission region of protons (p), deuterons (d) and tritons (t) has been characterized using a drift chamber while the particle time-of-flight, used to compute the kinetic energy spectra, was measured with a LYSO scintillator. The energy released in the LYSO crystal was used for particle identification purposes. The measurements were repeated with the setup at 60° and 90° with respect to the primary beam direction. The accuracy on the fragments emission profile reconstruction and its relationship with the Bragg peak position have been studied. Based on the acquired experimental evidence, a method to monitor the dose profile and the position of the Bragg peak inside the target is proposed.
The high dose conformity and healthy tissue sparing achievable in Particle Therapy when using C ions calls for safety factors in treatment planning, to prevent the tumor under-dosage related to the ...possible occurrence of inter-fractional morphological changes during a treatment. This limitation could be overcome by a range monitor, still missing in clinical routine, capable of providing on-line feedback. The Dose Profiler (DP) is a detector developed within the INnovative Solution for In-beam Dosimetry in hadronthErapy (INSIDE) collaboration for the monitoring of carbon ion treatments at the CNAO facility (Centro Nazionale di Adroterapia Oncologica) exploiting the detection of charged secondary fragments that escape from the patient. The DP capability to detect inter-fractional changes is demonstrated by comparing the obtained fragment emission maps in different fractions of the treatments enrolled in the first ever clinical trial of such a monitoring system, performed at CNAO. The case of a CNAO patient that underwent a significant morphological change is presented in detail, focusing on the implications that can be drawn for the achievable inter-fractional monitoring DP sensitivity in real clinical conditions. The results have been cross-checked against a simulation study.
•MC calculation of dose average LET and RBE evaluation.•Cross Sections for the production of secondary particles in proton therapy.•Calculation of fluence of secondary particles at different depth in ...water for the implementation in a TPS of next generation.
In proton therapy, secondary fragments are created in nuclear interactions of the beam with the target nuclei. The secondary fragments have low kinetic energies and high atomic numbers as compared to primary protons. Fragments have a high LET and deposit all their energy close to the generation point. For their characteristics, secondary fragments can alter the dose distribution and lead to an increase of RBE for the same delivered physical dose. Moreover, the radiobiological impact of target fragmentation is significant mostly in the region before the Bragg peak, where generally healthy tissues are present, and immediately after Bragg peak. Considering the high biological impact of those particles, especially in the case of healthy tissues or organs at risk, the inclusion of target fragmentation processes in the dose calculation of a treatment planning system can be relevant to improve the treatment accuracy and for this reason it is one of the major tasks of the MoVe IT project.
In this study, Monte Carlo simulations were employed to fully characterize the mixed radiation field generated by target fragmentation in proton therapy. The dose averaged LET has been evaluated in case of a Spread Out Bragg Peak (SOBP). Starting from LET distribution, RBE has been evaluated with two different phenomenological models. In order to characterize the mixed radiation field, the production cross section has been evaluated by means of the FLUKA code. The future development of present work is to generate a MC database of fragments fluence to be included in TPS.
The background induced by the high penetration power of the radiation is the main limiting factor of the current radio-guided surgery (RGS). To partially mitigate it, a RGS with β(+)-emitting ...radio-tracers has been suggested in literature. Here we propose the use of β(-)-emitting radio-tracers and β(-) probes and discuss the advantage of this method with respect to the previously explored ones: the electron low penetration power allows for simple and versatile probes and could extend RGS to tumours for which background originating from nearby healthy tissue makes probes less effective. We developed a β(-) probe prototype and studied its performances on phantoms. By means of a detailed simulation we have also extrapolated the results to estimate the performances in a realistic case of meningioma, pathology which is going to be our first in-vivo test case. A good sensitivity to residuals down to 0.1 ml can be reached within 1 s with an administered activity smaller than those for PET-scans thus making the radiation exposure to medical personnel negligible.
•The Dose Profiler is a charged fragment tracker designed for range monitoring in particle therapy.•The detector design, carefully optimized to operate in clinical environment, is described.•The ...characterization measurements have been performed using different experimental setup.•The obtained performances are suitable for range monitoring application.
Particle therapy (PT) can exploit heavy ions (such as He, C or O) to enhance the treatment efficacy, profiting from the increased Relative Biological Effectiveness and Oxygen Enhancement Ratio of these projectiles with respect to proton beams. To maximise the gain in tumor control probability a precise online monitoring of the dose release is needed, avoiding unnecessary large safety margins surroundings the tumor volume accounting for possible patient mispositioning or morphological changes with respect to the initial CT scan. The Dose Profiler (DP) detector, presented in this manuscript, is a scintillating fibres tracker of charged secondary particles (mainly protons) that will be operating during the treatment, allowing for an online range monitoring. Such monitoring technique is particularly promising in the context of heavy ions PT, in which the precision achievable by other techniques based on secondary photons detection is limited by the environmental background during the beam delivery. Developed and built at the SBAI department of “La Sapienza”, within the INSIDE collaboration and as part of a Centro Fermi flagship project, the DP is a tracker detector specifically designed and planned for clinical applications inside a PT treatment room. The DP operation in clinical like conditions has been tested with the proton and carbon ions beams of Trento proton-therapy center and of the CNAO facility. In this contribution the detector performances are presented, in the context of the carbon ions monitoring clinical trial that is about to start at the CNAO centre.
Organic scintillators are often chosen as radiation detectors for their fast decay time and their low Z, while inorganic ones are used when high light yields are required. In this paper we show that ...a para-terphenyl based detector has a blend of properties of the two categories that can be optimal for energy and position measurements of low-energy charged particles. Using 0.1% diphenylbutadiene doped para-terphenyl samples we measured a light attenuation length λ = 4.73 ±0.06 mm, a quenching factor for α particles Q α = (10.7 ±0.6), and a rejection power ranging between 3 - 11% for 660 keV photons, with respect to electrons of the same energy, depending on the signal threshold. A simulation based on FLUKA properly reproduces the experimental data distributions.
The treatment of deep-seated tumours with electrons of very high energies (VHEE, 70–150 MeV) has already been explored in the past, suggesting that a dosimetric coverage comparable with ...state-of-the-art proton (PT) or photon radiotherapy (RT) could be achieved with a large (
>
10) number of fields and high electron energy. The technical and economical challenges posed by the deployment of such beams in treatment centres, together with the expected small therapeutic gain, prevented the development of such technique. This scenario could radically change in the light of recent developments that occurred in the compact, high-gradient, electron acceleration technology and, additionally, of the experimental evidence of the sparing of organs at risk achieved in ultra-high dose rate irradiation, also referred to as FLASH. Electrons with the energy required to treat intracranial lesions could be provided, at dose rates compatible with what is needed to trigger the FLASH effect, by accelerators that are a few metres long, and the organ sparing could be exploited to significantly simplify the irradiation geometry, decreasing the number of fields needed to treat a patient. In this paper, the case of two patients affected by a chordoma and a meningioma, respectively, treated with protons in Trento (IT) is presented. The proton plans have been compared with VHEE plans and X-ray intensity-modulated radiotherapy (IMRT) plans. The VHEE plans were first evaluated in terms of physical dose distribution and then assuming that the FLASH regimen can be achieved. VHEE beams demonstrated their potential in obtaining plans that have comparable tumour coverage and organs at risk sparing when benchmarked against current state-of-the-art IMRT and PT. These results were obtained with a number of explored fields that was in the range between 3 and 7, consistent with what is routinely performed in IMRT and PT conventional irradiations. The FLASH regimen, in all cases, showed its potential in reducing damage to the organs placed nearby the target volume, allowing, particularly in the chordoma case where the irradiation geometry is more challenging, a better tumour coverage with respect to the conventional treatments.
Purpose:
Intraoperative electron radiotherapy (IOeRT) is considered the first clinical translation of FLASH with electrons. A crucial aspect is represented by the precise dose monitoring and ...measurement; to this aim, we propose a method fully based on Monte Carlo (MC) simulation that uses as input the beam current measurement and the beam optics simulation. To validate this approach, we chose the NOVAC11 (produced by Sordina IORT Technologies SpA) accelerator, which provides a well-studied model.
Methods:
We used FLUKA and FRED MC software to simulate in detail the geometry of the NOVAC11 and the coupled applicator usually adopted in clinical practice to deliver the dose in the surgical bed. The simulation results of the longitudinal and off-axis profiles and dose per pulse obtained in a water phantom with different applicators are compared to the experimental data.
Results:
A very good agreement not only for the relative dosimetry in both the longitudinal and off-axis profiles, with a gamma index pass rate of 100% with 3%/3 mm acceptance criteria, but also for the absolute dosimetry was obtained.
Conclusion:
The results completely validate the MC description of the system and provide a reliable evaluation of the dose per pulse and output factor with an accuracy of the order of few % for different sets of applicator diameters and lengths.
PDF
