In Vitro Comparison of Passive and Active Clinical Proton Beams.

Nowadays, the irradiation methodology in proton therapy is switching from the use of passively scattered beams to active pencil beams due to the possibility of more conformal dose distributions. The dose rates of active pencil beams are much higher than those of passive beams. The purpose of this study was to investigate whether there is any difference in the biological effectiveness of these passive and active irradiation modes. The beam qualities of double scattering and pencil beam scanning were measured dosimetrically and simulated using the Monte Carlo code. Using the medulloblastoma cell line DAOY, we performed an in vitro comparison of the two modes in two positions along the dose-deposition curve plateau and inside the Bragg peak. We followed the clonogenic cell survival, apoptosis, micronuclei, and γH2AX assays as biological endpoints. The Monte Carlo simulations did not reveal any difference between the beam qualities of the two modes. Furthermore, we did not observe any statistically significant difference between the two modes in the in vitro comparison of any of the examined biological endpoints. Our results do not show any biologically relevant differences related to the different dose rates of passive and active proton beams.

Harmonization of proton treatment planning for head and neck cancer using pencil beam scanning: first report of the IPACS collaboration group.

Background and purpose: A collaborative network between proton therapy (PT) centres in Trento in Italy, Poland, Austria, Czech Republic and Sweden (IPACS) was founded to implement trials and harmonize PT. This is the first report of IPACS with the aim to show the level of harmonization that can be achieved for proton therapy planning of head and neck (sino-nasal) cancer.Methods: CT-data sets of five patients were included. During several face-to-face and online meetings, a common treatment planning protocol was developed. Each centre used its own treatment planning system (TPS) and planning approach with some restrictions specified in the treatment planning protocol. In addition, volumetric modulated arc therapy (VMAT) photon plans were created.Results: For CTV1, the average Dmedian was 59.3 ± 2.4 Gy(RBE) for protons and 58.8 ± 2.0 Gy(RBE) for VMAT (aim was 56 Gy(RBE)). For CTV2, the average Dmedian was 71.2 ± 1.0 Gy(RBE) for protons and 70.6 ± 0.4 Gy(RBE) for VMAT (aim was 70 Gy(RBE)). The average D2% for the spinal cord was 25.1 ± 8.5 Gy(RBE) for protons and 47.6 ± 1.4 Gy(RBE) for VMAT. The average D2% for chiasm was 46.5 ± 4.4 Gy(RBE) for protons and 50.8 ± 1.4 Gy(RBE) for VMAT, respectively. Robust evaluation was performed and showed the least robust plans for plans with a low number of beams.Discussion: In conclusion, several influences on harmonization were identified: adherence/interpretation to/of the protocol, available technology, experience in treatment planning and use of different beam arrangements. In future, all OARs that should be included in the optimization need to be specified in order to further harmonize treatment planning.

Clinical practice in European centres treating paediatric posterior fossa tumours with pencil beam scanning proton therapy.

BACKGROUND AND PURPOSE: As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing. MATERIALS AND METHODS: A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning. Each centre planned two PF tumour cases for focal irradiation, according to their own clinical practice but based on common delineations. The prescription dose was 54 Gy(RBE) for Case 1 and 59.4 Gy(RBE) for Case 2. For both cases, planning strategies and relevant dose metrics were compared. RESULTS: Seventeen (89 %) centres answered the survey, and sixteen (80 %) participated in the treatment planning comparison. In the survey, thirteen (68 %) centres reported using the European Particle Therapy Network definition for brainstem delineation. In the treatment planning study, while most centres used three beam directions, their configurations varied widely across centres. Large variations were also seen in brainstem doses, with a brainstem near maximum dose (D2%) ranging from 52.7 Gy(RBE) to 55.7 Gy(RBE) (Case 1), and from 56.8 Gy(RBE) to 60.9 Gy(RBE) (Case 2). CONCLUSION: This study assessed the European PBS-PT planning of paediatric PF tumours. Agreement was achieved in e.g. delineation-practice, while wider variations were observed in planning approach and consequently dose to organs at risk. Collaboration between centres is still ongoing, striving towards common guidelines.

5-Years Analysis of Effectivity and Toxicity of Ultra-Hypofractionated Proton Radiotherapy in the Treatment of Low- and Intermediate-Risk Prostate Cancer-A Retrospective Analysis.

BACKGROUND: We retrospectively analyzed the 5-year biochemical disease-free survival (bDFS) and occurrence of late toxicity in prostate cancer patients treated with pencil beam scanning (PBS) proton radiotherapy. METHODOLOGY: In the period from January 2013 to June 2018, 853 patients with prostate cancer were treated with an ultra-hypofractionated schedule (36.25 GyE/five fractions). The mean PSA value was 6.7 (0.7-19.7) µg/L. There were 318 (37.3%), 314 (36.8%), and 221 (25.9%) patients at low (LR), favorable intermediate (F-IR), and unfavorable intermediate risk (U-IR), respectively. Neoadjuvant hormonal therapy was administered to 197 (23.1%) patients, and 7 (0.8%) patients had adjuvant hormonal therapy. The whole group of patients reached median follow-up time at 62.7 months, and their mean age was 64.8 (40.0-85.7) years. The bDFS rates and late toxicity profile were evaluated. RESULTS: Median treatment time was 10 (7-38) days. Estimated 5-year bDFS rates were 96.5%, 93.7%, and 91.2% for low-, favorable intermediate-, and unfavorable intermediate-risk groups, respectively. Cumulative late toxicity (CTCAE v4.0) of G2+ was as follows: gastrointestinal (GI)-G2: 9.1%; G3: 0.5%; genitourinary (GU)-G2: 4.3%, and no G3 toxicity was observed. PSA relapse was observed in 58 (6.8%) patients: 16 local, 22 lymph node, 4 bone recurrences, and 10 combined sites of relapse were detected. Throughout the follow-up period, 40 patients (4.7%) died, though none due to prostate cancer. CONCLUSION: Ultra-hypofractionated proton beam radiotherapy is an effective treatment for low- and favorable intermediate-risk prostate cancer, with long-term bDFS rates comparable to other techniques. It is promising for unfavorable intermediate-risk prostate cancer and has acceptable long-term GI and favorable GU toxicity.

Pencil-beam scanning proton therapy for the treatment of glomus jugulare tumours.

INTRODUCTION: Glomus jugulare tumours (GJT) are benign tumours that arise locally and destructively in the base of the skull and can be successfully treated with radiotherapy. Patients have a long-life expectancy and the late effects of radiotherapy can be serious. Proton radiotherapy reduces doses to critical organs and can reduce late side effects of radiotherapy. The aim of this study was to report feasibility and early clinical results of 12 patients treated using proton therapy. METHODS: Between December 2013 and June 2019, 12 patients (pts) with GJT (median volume 20.4 cm3 ; range 8.5-41 cm3 ) were treated with intensity modulated proton therapy (IMPT). Median dose was 54 GyE (Gray Equivalents) (50-60 GyE) with daily fractions of 2 GyE. Twelve patients were analysed with a median follow-up time of 42.2 months (11.3-86.7). Feasibility, dosimetric parameters, acute and late toxicity and local effect on tumour were evaluated in this retrospective study. RESULTS: All patients finished treatment without interruption, with excellent dosimetric parameters and mild acute toxicity. Stabilisation of tumour size was detected on MRI in all patients. No changes in symptoms were observed in comparison with pre-treatment conditions. No late effects of radiotherapy were observed. CONCLUSION: Pencil-beam scanning proton radiotherapy is highly feasible in the treatment of large GJT with mild acute toxicity and promising short-term results. Longer follow-up and larger patient cohorts are required to further identify the role of pencil-beam scanning (PBS) for this indication.

Accelerated radiotherapy with concomitant boost technique (69.5 Gy/5 weeks) : an alternative in the treatment of locally advanced head and neck cancer.

BACKGROUND AND PURPOSE: To present the feasibility and results of accelerated radiotherapy with concomitant boost technique (69.5 Gy/5 weeks) in the treatment of locally advanced head and neck cancer. PATIENTS AND METHODS: A total of 65 patients were treated between June 2006 and August 2009. The distribution of clinical stages was as follows: II 11%, III 23%, IV 61%, and not defined 5%. RESULTS: The median follow-up was 30.5 months. The treatment plan was completed in 94% of patients. Patients were treated using the conformal or intensity-modulated radiotherapy (IMRT) technique. The median overall treatment time was 37 days (13-45 days). The mean radiotherapy dose was 68.4 Gy (16-74 Gy). Overall survival was 69% after 2 years. Disease-free survival was 62% after 2 years. Acute toxicity ≥ grade 3(RTOG scale) included mucositis (grade 3: 42.6%), pharynx (grade 3: 42.3%), skin (grade 3: 9.5%), larynx (grade 3: 4%), while late toxicity affected skin (grade 3: 6.25%) and salivary glands (grade 3: 3.7%). CONCLUSION: Accelerated radiotherapy with concomitant boost technique is feasible in patients with locally advanced head and neck cancer, has an acceptable toxicity profile, and yields promising treatment results.

Ultra-Hypofractionated Proton Therapy in Localized Prostate Cancer: Passive Scattering versus Intensity-Modulated Proton Therapy.

Few studies have directly compared passive scattering (PS) to intensity-modulated proton therapy (IMPT) in the delivery of ultra-hypofractionated proton beams to the localized prostate cancer (PCa). In this preliminary study involving five patients previously treated with CyberKnife, treatment plans were created for PS and IMPT (36.25 CGE in five fractions with two opposing fields) to compare the dosimetric parameters to the planning target volume (PTV) and organs-at-risk (OAR: rectum, bladder, femoral heads). Both plans met the acceptance criteria. Significant differences were observed in the minimum and maximum doses to the PTV. The mean dose to the PTV was lower for PS (35.62 ± 0.26 vs. 37.18 ± 0.14; p = 0.002). Target coverage (D98%) was better for IMPT (96.79% vs. 99.10%; p = 0.004). IMPT resulted in significantly lower mean doses to the rectum (16.75 CGE vs. 6.88 CGE; p = 0.004) and bladder (17.69 CGE vs. 5.98 CGE p = 0.002). High dose to the rectum (V36.25 CGE) were lower with PS, but not significantly opposite to high dose to the bladder. No significant differences were observed in mean conformity index values, with a non-significant trend towards higher mean homogeneity index values for PS. Non-significant differences in the gamma index for both fields were observed. These findings suggest that both PS and IMPT ultra-hypofractionated proton therapy for PCa are highly precise, offering good target coverage and sparing of normal tissues and OARs.

Pencil Beam Scanning (PBS) Intensity-Modulated Proton Therapy (IMPT) Chemoradiotherapy for Anal Canal Cancer-Single Institution Experience.

Background: A favourable dose distribution has been described for proton beam therapy (PBT) of anal cancer in dosimetric studies. The relationship between dosimetric parameters in bone marrow and haematologic toxicity, treatment interruptions, and treatment efficacy has also been documented. There are only few references on clinical results of PBT for anal cancer. The primary objective of the retrospective study was to assess the efficacy of pencil beam scanning intensity-modulated proton therapy (PBS IMPT) in the definitive chemoradiotherapy of anal cancer. Secondary objectives were established to identify the risks of acute chronic toxicity risks and to assess colostomy rates. Materials and methods: Patients were treated for biopsy-proven squamous cell cancer (SCC) of the anus at initial or advanced stages. Eligible patients received PBS IMPT at a single institution. Treatment was administered in two volumes: 1-tumour with margins plus involved lymph nodes; 2-regional lymph node groups: perirectal (mesorectal), obturatory, inguinal, internal, external, and common iliac. The total doses of 57.5 GyE and 45 GyE, respectively, were administered in volumes 1 and 2 in 25 fractions, 5 fractions per week, respectively (a simultaneous integrated boost). Concomitant chemotherapy cisplatinum (CDDP) plus 5-FU or CDDP plus capecitabine was administered as per protocol. The treatment effect was assessed using DRE (digital rectal examination) and MRI (magnetic resonance imaging) within the follow-up period. Toxicity was scaled using CTCAE version 4.0 criteria. Results: 39 of 41 patients treated during the period of February 2014-August 2021 were eligible for analysis. All patients completed treatment, 76.9% without interruption. The median treatment time was 35 days (32-35). The median follow-up period was 30 months, 34 patients are alive to-date, 5 patients died prior to the date of analysis, and 2 deaths were unrelated to the primary disease. The 2-year overall survival, relapse-free survival, and colostomy-free survival were 94.2%, 93.8%, and 91.0%, respectively. Complete regression was achieved in 36 patients (92.3%), partial regression was achieved in 2 (5.1%), and immediate progression at end of treatment occurred in 1 patient (2.6%). Salvage resection was indicated for two patients in partial regression and due to severe chronic dermatologic toxicity. The grade 3 and 4 haematological toxicity rates were 7.7% and 5.1%, respectively. The most frequent non-haematological acute toxicities of grade 3-4 observed were dermatitis (23.1%), diarrhoea (7.7%), and dehydration (7.7%). Chronic toxicity emerged predominantly as skin atrophy/ulceration grade 2 (26.5%) and grade 3-4 (5.8%), and radiation proctitis grade 2 (38.2%) and grade 3 (2.9%). Discussion, conclusions: This single-institution study showed the high efficacy of PBS IMPT, achieving a high rate of complete regression. The haematological acute toxicity of grade 3-4 remained low; however, the impact of altered chemotherapy (CDDP instead of mitomycin C) remains unclear. The incidence of other acute toxicities shares similarity with photon therapy investigated in large studies. The acute toxicity completely resolved in all patients, had no lethal outcomes, and never resulted in the necessity for colostomy. By contrast, it was chronic toxicity, skin ulceration, perirectal fistulation, and fibrosis that resulted in salvage surgery and/or the need for a colostomy. A challenging question remains: to what extent can PBT prevent chronic toxicity? Longer follow-up remains necessary.

Ultrahypofractionated Proton Radiation Therapy in the Treatment of Low and Intermediate-Risk Prostate Cancer-5-Year Outcomes.

PURPOSE: To analyze the 5-year biochemical disease-free survival (bDFS) and late toxicity profile in patients with prostate cancer treated with pencil beam scanning (PBS) proton radiation therapy. METHODS AND MATERIALS: Between January 2013 and March 2016, 284 patients with prostate cancer were treated using intensity modulated proton therapy (IMPT), with an ultrahypofractionated schedule (36.25 GyE in 5 fractions). Five patients were immediately lost from follow-up and thus were excluded from analysis. Data for 279 patients were prospectively collected and analyzed with a median follow-up time of 56.5 (range, 3.4-87.5) months. The mean age at time of treatment was 64.5 (40.1-85.7) years, and the median prostate-specific antigen (PSA) value was 6.35 µg/L (0.67-17.3 µg/L). A total of 121 (43.4%) patients had low-risk, 125 patients (44.8%) had favorable, and 33 (11.8%) unfavorable intermediate-risk cancer. In addition, 49 (17.6%) patients underwent neoadjuvant hormonal therapy, and no patients had adjuvant hormonal therapy. bDFS and late toxicity profiles were evaluated. RESULTS: The median treatment time was 9 days (range, 7-18 days). The 5-year bDFS was 96.9%, 91.7%, and 83.5% for the low-, favorable, and unfavorable intermediate-risk group, respectively. Late toxicity (Common Terminology Criteria for Adverse Events v.4) was as follows: gastrointestinal: grade 1, 62 patients (22%), grade 2, 20 patients (7.2%), and grade 3, 1 patient (0.36%); genitourinary: grade 1, 80 patients (28.7%), grade 2, 14 patients (5%), and grade 3, 0 patients. PSA relapse was observed in 17 patients (6.1%), and lymph node or bone recurrence was detected in 11 patients. Four (1.4%) local recurrences were detected. Nine patients (3.2%) died of causes unrelated to prostate cancer. No deaths related to prostate cancer were reported. CONCLUSION: Ultrahypofractionated proton beam radiation therapy for prostate cancer is effective with long-term bDFS comparable with other fractionation schedules and with minimal serious long-term GI and GU toxicity.

LOW DOSE BATH FROM IMPT VS. IMXT FOR THE PELVIC AREA WHEN TREATING ADVANCED PROSTATE CANCER.

Twenty (10 intensity-modulated proton therapy (IMPT) and 10 intensity-modulated x-ray therapy (IMXT) treatment plans for patients with advanced prostate carcinoma were compared in this study. All chosen patients were indicated for prostate and pelvic lymph nodes irradiation using simultaneous integrated boost technique. These patients represent typical specimen for this diagnose. IMPT irradiates just half of the tissue volume with a low dose (up to 10 cobalt gray equivalent) compared to IMXT without compromise in target volumes coverage and in this way reduces the risk of secondary cancer development or other possible complications.

Extreme hypofractionated proton radiotherapy for prostate cancer using pencil beam scanning: Dosimetry, acute toxicity and preliminary results.

INTRODUCTION: Extreme hypofractionated radiotherapy for prostate cancer is a common modality in photon therapy. Pencil beam scanning (PBS) in similar fractionation allows better dose distribution and makes proton therapy more available for such patients. The purpose of this study is the feasibility of extreme proton hypofractionated radiotherapy and publication of early clinical results. METHODS: Two hundred patients with early-stage prostate cancer were treated with IMPT (intensity-modulated proton therapy), extreme hypofractionated schedule (36.25 GyE in five fractions) between February 2013 and December 2015. Mean age of the patients was 64.3 years, and the mean value of prostate-specific antigen (PSA) before treatment was 6.83 µg/L (0.6-17.3 µg/L). Ninety-three patients (46.5%) were in the low-risk group. One hundred and seven patients (53.5%) were in the intermediate-risk group. Twenty-nine patients (14.5%) had neoadjuvant hormonal therapy, and no patients had adjuvant hormonal therapy. Acute toxicity, late toxicity and short-term results were evaluated. RESULTS: All patients finished radiotherapy without interruptions. The median follow-up time was 36 months. The mean treatment time was 9.5 days (median 9 days). Acute toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 was (gastrointestinal toxicity) GI (grade) G1-17%, G2-3.5%; (genitourinary toxicity) GU G1-40%, G2-19%; and no G3 toxicity was observed. Late toxicity was GI G1-19%, G2-5.5%; GU G1-17%, G2-4%; and no G3 toxicity was observed. PSA relapse was observed in one patient (1.08%) in the low-risk group (pelvic lymph node involvement was detected) and in seven patients (6.5%) in the intermediate-risk group (three lymph node metastases, two lymph node and bone metastases, two PSA relapses). No patient died of prostate cancer, and three patients died from other reasons. No local recurrence of cancer in the prostate was observed. CONCLUSIONS: Proton beam radiotherapy for prostate cancer is feasible with a low rate of acute toxicity and promising late toxicity and effectivity.

Relative biological effectiveness in a proton spread-out Bragg peak formed by pencil beam scanning mode.

In recent years, there is an increased interest in using scanning modes in proton therapy, due to the more conformal dose distributions, thanks to the spot-weighted dose delivery. The dose rate in each spot is however much higher than the dose rate when using passive irradiation modes, which could affect the cell response. The purpose of this work was to investigate how the relative biological effectiveness changes along the spread-out Bragg peak created by protons delivered by the pencil beam scanning mode. Cell survival and micronuclei formation were investigated in four positions along the spread-out Bragg peak for various doses. Monte Carlo simulations were used to estimate the dose-averaged linear energy transfer values in the irradiation positions. The cell survival was found to decrease the deeper the sample was placed in the spread-out Bragg peak, which corresponds to the higher linear energy transfer values found using Monte Carlo simulations. The micronuclei frequencies indicate more complex cell injuries at that distal position compared to the proximal part of the spread-out Bragg peak. The relative biological effectiveness determined in this study varies significantly and systematically from 1.1, which is recommended value by the International Commission on Radiation Units, in all the studied positions. In the distal position of spread-out Bragg peak the relative biological effectiveness values were found to be 2.05 ± 0.44, 1.85 ± 0.42, 1.53 ± 0.38 for survival levels 90, 50 and 10%, respectively.

Profile of European proton and carbon ion therapy centers assessed by the EORTC facility questionnaire.

BACKGROUND: We performed a survey using the modified EORTC Facility questionnaire (pFQ) to evaluate the human, technical and organizational resources of particle centers in Europe. MATERIAL AND METHODS: The modified pFQ consisted of 235 questions distributed in 11 sections accessible on line on an EORTC server. Fifteen centers from 8 countries completed the pFQ between May 2015 and December 2015. RESULTS: The average number of patients treated per year and per particle center was 221 (range, 40-557). The majority (66.7%) of centers had pencil beam or raster scanning capability. Four (27%) centers were dedicated to eye treatment only. An increase in the patients-health professional FTE ratio was observed for eye tumor only centers when compared to other centers. All centers treated routinely chordomas/chondrosarcomas, brain tumors and sarcomas but rarely breast cancer. The majority of centers treated pediatric cases with particles. Only a minority of the queried institutions treated non-static targets. CONCLUSIONS: As the number of particle centers coming online will increase, the experience with this treatment modality will rise in Europe. Children can currently be treated in these facilities in a majority of cases. The majority of these centers provide state of the art particle beam therapy.

Experimental and Monte Carlo studies of fluence corrections for graphite calorimetry in low- and high-energy clinical proton beams.

PURPOSE: The aim of this study was to determine fluence corrections necessary to convert absorbed dose to graphite, measured by graphite calorimetry, to absorbed dose to water. Fluence corrections were obtained from experiments and Monte Carlo simulations in low- and high-energy proton beams. METHODS: Fluence corrections were calculated to account for the difference in fluence between water and graphite at equivalent depths. Measurements were performed with narrow proton beams. Plane-parallel-plate ionization chambers with a large collecting area compared to the beam diameter were used to intercept the whole beam. High- and low-energy proton beams were provided by a scanning and double scattering delivery system, respectively. A mathematical formalism was established to relate fluence corrections derived from Monte Carlo simulations, using the fluka code [A. Ferrari et al., "fluka: A multi-particle transport code," in CERN 2005-10, INFN/TC 05/11, SLAC-R-773 (2005) and T. T. Böhlen et al., "The fluka Code: Developments and challenges for high energy and medical applications," Nucl. Data Sheets 120, 211-214 (2014)], to partial fluence corrections measured experimentally. RESULTS: A good agreement was found between the partial fluence corrections derived by Monte Carlo simulations and those determined experimentally. For a high-energy beam of 180 MeV, the fluence corrections from Monte Carlo simulations were found to increase from 0.99 to 1.04 with depth. In the case of a low-energy beam of 60 MeV, the magnitude of fluence corrections was approximately 0.99 at all depths when calculated in the sensitive area of the chamber used in the experiments. Fluence correction calculations were also performed for a larger area and found to increase from 0.99 at the surface to 1.01 at greater depths. CONCLUSIONS: Fluence corrections obtained experimentally are partial fluence corrections because they account for differences in the primary and part of the secondary particle fluence. A correction factor, F(d), has been established to relate fluence corrections defined theoretically to partial fluence corrections derived experimentally. The findings presented here are also relevant to water and tissue-equivalent-plastic materials given their carbon content.

Investigating the Implications of a Variable RBE on Proton Dose Fractionation Across a Clinical Pencil Beam Scanned Spread-Out Bragg Peak.

PURPOSE: To investigate the clinical implications of a variable relative biological effectiveness (RBE) on proton dose fractionation. Using acute exposures, the current clinical adoption of a generic, constant cell killing RBE has been shown to underestimate the effect of the sharp increase in linear energy transfer (LET) in the distal regions of the spread-out Bragg peak (SOBP). However, experimental data for the impact of dose fractionation in such scenarios are still limited. METHODS AND MATERIALS: Human fibroblasts (AG01522) at 4 key depth positions on a clinical SOBP of maximum energy 219.65 MeV were subjected to various fractionation regimens with an interfraction period of 24 hours at Proton Therapy Center in Prague, Czech Republic. Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and parameterized using a linear quadratic formalism. RESULTS: Significant variations in the cell killing RBE for fractionated exposures along the proton dose profile were observed. RBE increased sharply toward the distal position, corresponding to a reduction in cell sparing effectiveness of fractionated proton exposures at higher LET. The effect was more pronounced at smaller doses per fraction. Experimental survival fractions were adequately predicted using a linear quadratic formalism assuming full repair between fractions. Data were also used to validate a parameterized variable RBE model based on linear α parameter response with LET that showed considerable deviations from clinically predicted isoeffective fractionation regimens. CONCLUSIONS: The RBE-weighted absorbed dose calculated using the clinically adopted generic RBE of 1.1 significantly underestimates the biological effective dose from variable RBE, particularly in fractionation regimens with low doses per fraction. Coupled with an increase in effective range in fractionated exposures, our study provides an RBE dataset that can be used by the modeling community for the optimization of fractionated proton therapy.

Spectral fluence of neutrons generated by radiotherapeutic linacs.

Spectral fluences of neutrons generated in the heads of the radiotherapeutic linacs Varian Clinac 2100 C/D and Siemens ARTISTE were measured by means of the Bonner spheres spectrometer whose active detector of thermal neutrons was replaced by an activation detector, i.e. a tablet made of pure manganese. Measurements with different collimator settings reveal an interesting dependence of neutron fluence on the area defined by the collimator jaws. The determined neutron spectral fluences were used to derive ambient dose equivalent rate along the treatment coach. To clarify at which components of the linac neutrons are mainly created, the measurements were complemented with MCNPX calculations based on a realistic model of the Varian Clinac.

Video-assisted multivessel revascularization through a left anterior small thoracotomy approach with the Symmetry Aortic Connector System.

OBJECTIVE: We sought to demonstrate the applicability of video-assisted multivessel revascularization through a left anterior small thoracotomy approach with the use of the Symmetry Aortic Connector System (St Jude Medical Anastomotic Technology Group, Inc, St Paul, Minn) as an alternative to the standard median sternotomy approach and to evaluate predischarge angiographically documented graft patency. METHODS: From October 2001 through February 2002, a total of 15 patients with triple-vessel disease were operated on through a left anterior small thoracotomy approach with video-assisted port-access construction of proximal aorta-to-saphenous vein anastomoses with the Symmetry Aortic Connector System and cardiopulmonary bypass with femoral cannulation and without cardioplegic arrest. There were 9 male and 6 female subjects with a mean age of 68.3 +/- 3.6 years and an average ejection fraction of 55.8% +/- 19.6%. Subject inclusion criteria consisted of female sex (initially but not throughout the study), coronary artery reoperations, and sternal bone disease. Subject exclusion criteria consisted of an age younger than 65 years, extensive atheromatous plaques in the ascending aorta, and aortoiliac occlusive disease. All but 1 patient underwent angiographic patency evaluation before discharge. RESULTS: Fifteen operations were performed successfully without any deaths. Twenty-nine sutureless proximal anastomoses were performed, with an average of 3.13 +/- 0.62 distal anastomoses per patient. Eleven (73%) patients underwent a fast track protocol with extubation in the operating room. We did not observe any instances of low cardiac output syndrome, stroke, renal insufficiency, wound complication, or perioperative myocardial infarction. A single episode of atrial fibrillation occurred in this group. Angiographic assessment of 44 bypass grafts and target arteries was performed, and 86% of those examined were widely patent (FitzGibbon score A). CONCLUSIONS: We have demonstrated a potential advantage of the sutureless Symmetry Aortic Connector System as a suitable approach that affords minimal access. Video-assisted multivessel revascularization through a left anterior small thoracotomy approach with an automated mechanical anastomosis device is particularly useful in patients undergoing coronary artery bypass reoperations or those at risk of poor sternal healing or infection. This approach seems to be a safe alternative to standard median sternotomy.

Port access video-assisted proximal anastomosis with the symmetry aortic connector in MIDCABG procedure.

We present an alternative way to create a video-assisted port access proximal anastomosis in the ascending aorta with the Symmetry Bypass System Aortic Connector (St. Jude Medical ATG, St. Paul, MN). This technique was successfully used in a patient undergoing urgent minimally invasive direct coronary artery bypass grafting (MIDCABG), in whom the left internal mammary artery was not harvested owing to subtotal occlusion of the left subclavian artery. Port access use of mechanical anastomotic devices may increase the indications for minimally invasive coronary artery surgery.