Complications after proton radiotherapy in children, focusing on severe late complications. A complete Swedish cohort 2008-2019.

BACKGROUND: Proton radiotherapy (RT) is an attractive tool to deliver local therapy with minimal dose to uninvolved tissue, however, not suitable for all patients. The aim was to explore complications, especially severe late complications (grades 3-4), following proton RT delivered to a complete Swedish cohort of paediatric patients aged <18 years treated 2008-2019. MATERIAL AND METHODS: Data was downloaded from a national registry. Complications with a possible causation with RT are reported. Proton treatments until July 2015 was performed with a fixed horizontal 172 MeV beam (The Svedberg Laboratory (TSL), Uppsala) in a sitting position and thereafter with gantry-based pencil-beam scanning technique (Skandion Clinic, Uppsala) in a supine position. RESULTS: 219 courses of proton RT (77 at TSL and 142 at Skandion) were delivered to 212 patients (mean age 9.2 years) with various tumour types (CNS tumours 58%, sarcomas 26%, germ cell tumours 7%). Twenty-five patients had severe acute complications (skin, mucous membrane, pharynx/oesophagus, larynx, upper gastrointestinal canal, lower gastrointestinal canal, eyes, ears). Fifteen patients had severe late complications; with increased proportion over time: 4% at 1-year follow-up (FU), 5% at 3-year, 11% at 5-year. Organs affected were skin (1 patient), subcutaneous tissue (4), salivary glands (1), upper GI (1), bone (7), joints (2), CNS (2), PNS (1), eyes (1) and ears (5). Twenty-one of the 28 patients with 10-year FU had at least one late complication grades 1-4 and fourteen of them had more than one (2-5 each). CONCLUSION: The most important result of our study is the relatively low proportion of severe late complications, comparable with other proton studies on various tumours. Furthermore, the numbers of late complications are lower than our own data set on a mixed population of photon and proton treated paediatric patients, assuring the safety of using proton therapy also in the clinical practice.

Neurocognition and mean radiotherapy dose to vulnerable brain structures: new organs at risk?

BACKGROUND: Children with brain tumors are at high risk of neurocognitive decline after radiotherapy (RT). However, there is a lack of studies on how RT doses to organs at risk (OARs) impacts neurocognition. The aim of this study was to examine dose-risk relationships for mean RT dose to different brain structures important for neurocognitive networks. We explored previously established OARs and potentially new OARs. METHODS: A sample of 44 pediatric brain tumor survivors who had received proton and/or photon RT were included. Correlations between mean RT doses to OARs and IQ were analyzed. Previously established OARs were cochleae, optic chiasm, optic nerve, pituitary gland, hypothalamus, hippocampus and pons. Potential new OARs for RT-induced neurocognitive decline were cerebellum, vermis and thalamus. RESULTS: Mean RT dose to different OARs correlated with several IQ subtests. Higher mean RT dose to cochleae, optic nerve, cerebellum, vermis and pons was correlated with lower performance on particularly full-scale IQ (FIQ), Perceptual Reasoning (PRI), Working Memory (WMI) and Processing Speed Index (PSI). Higher mean RT dose to hippocampus correlated with lower performance on processing speed and working memory. For those receiving whole brain RT (WBRT), higher mean RT dose to the pituitary gland correlated with lower performance on working memory. CONCLUSION: A high dose-risk correlation was found between IQ subtests and mean RT dose in established and potential new OARs. Thus, in the lack of validated dose constraints for vulnerable brain structures, a parsimonious approach in RT planning should be considered to preserve neurocognitive networks.

Evaluation of four surface surrogates for modeling lung tumor positions over several fractions in radiotherapy.

Patient breathing during lung cancer radiotherapy reduces the ability to keep a sharp dose gradient between tumor and normal tissues. To mitigate detrimental effects, accurate information about the tumor position is required. In this work, we evaluate the errors in modeled tumor positions over several fractions of a simple tumor motion model driven by a surface surrogate measure and its time derivative. The model is tested with respect to four different surface surrogates and a varying number of surrogate and image acquisitions used for model training. Fourteen patients were imaged 100 times with cine CT, at three sessions mimicking a planning session followed by two treatment fractions. Patient body contours were concurrently detected by a body surface laser scanning system BSLS from which four surface surrogates were extracted; thoracic point TP, abdominal point AP, the radial distance mean RDM, and a surface derived volume SDV. The motion model was trained on session 1 and evaluated on sessions 2 and 3 by comparing modeled tumor positions with measured positions from the cine images. The number of concurrent surrogate and image acquisitions used in the training set was varied, and its impact on the final result was evaluated. The use of AP as a surface surrogate yielded the smallest error in modeled tumor positions. The mean deviation between modeled and measured tumor positions was 1.9 mm. The corresponding deviations for using the other surrogates were 2.0 mm (RDM), 2.8 mm (SDV), and 3.0 mm (TP). To produce a motion model that accurately models the tumor position over several fractions requires at least 10 simultaneous surrogate and image acquisitions over 1-2 minutes.

Evaluation of irregular breathing effects on internal target volume definition for lung cancer radiotherapy.

PURPOSE: Irregular breathing may compromise the treated volume for free-breathing lung cancer patients during radiotherapy. We try to find a measure based on a breathing amplitude surrogate that can be used to select the patients who need further investigation of tumor motion to ensure that the internal target volume (ITV) provides reliant coverage of the tumor. MATERIAL AND METHODS: Fourteen patients were scanned with four-dimensional computed tomography (4DCT) during free-breathing. The breathing motion was detected by a pneumatic bellows device used as a breathing amplitude surrogate. In addition to the 4DCT, a breath-hold (BH) scan and three cine CT imaging sessions were acquired. The cine images were taken at randomized intervals at a rate of 12 per minute for 8 minutes to allow tumor motion determination during a typical hypo-fractionated treatment scenario. A clinical target volume (CTV) was segmented in the BH CT and propagated over all cine images and 4DCT bins. The center-of-volume of the translated CTV (CTVCOV ) in the ten 4DCT bins were interconnected to define the 4DCT determined tumor trajectory (4DCT-TT). The volume of CTV inside ITV for all cine CTs was calculated and reported at the 10th percentile (VCTV10% ). The deviations between CTVCOV in the cine CTs and the 4DCT-TT were calculated and reported at its 90th percentile (d90% ). The standard deviation of the bellows amplitude peaks (SDP) and the ratio between large and normal inspirations, κrel , were tested as surrogates for VCTV10% and d90% . RESULTS: The values of d90% ranged from 0.6 to 5.2 mm with a mean of 2.2 mm. The values of VCTV10% ranged from 59-93% with a mean of 78 %. The SDP had a moderate correlation (r = 0.87) to d90% . Less correlation was seen between SDP and VCTV10% (r = 0.77), κrel and d90% (r = 0.75) and finally κrel and VCTV10% (r = 0.75). CONCLUSIONS: The ITV coverage had a large variation for some patients. SDP seems to be a feasible surrogate measure to select patients that needs further tumor motion determination.

High efficacy of hypofractionated proton therapy with 4 fractions of 5 Gy as a boost to 50 Gy photon therapy for localized prostate cancer.

PURPOSE: We report the outcome of hypofractionated proton boost as an alternative to high dose-rate brachytherapy boost, aimed at an equivalent dose exceeding 86 Gy in 2 Gy fractions, for patients with localized prostate cancer and all risk groups. METHODS: Proton boost of 20 Gy given in 4 daily fractions to the prostate was followed after a one-week rest by photon therapy to 50 Gy in 2 Gy fractions. Outcomes are presented per risk group according to both NCCN and ISUP classifications. Advanced imaging was performed for adequate staging, and at an early stage of rising PSA, to identify the relapse site. Endpoints were PSA relapse-free-, locoregional relapse-free-, and distant metastasis-free- survival. Prostate cancer-specific-, metastasis-free-, and overall survival were also estimated. Genitourinary (GU) and gastrointestinal (GI) toxicity were based on patients' questionnaires and physicians' records. RESULTS: We treated 531 patients between 2002 and 2015; 504 had localized disease. The cohort included 180 patients with T3/T4 disease (36%). The majority of the 50% with high-/very high-risk disease received ADT, 9-24 months; 92 had adjuvant pelvic node treatment. Median follow-up was 113 months (43-193). For low-, intermediate-, high-, and very high-risk patients, the 5-year PSA relapse-free survival was 100%, 94%, 82%, and 72%, respectively. Prolonged ADT improved biochemical control and nodal treatment regional control. The NCCN classification had higher predictive discrimination than the ISUP classification. The 5-year prevalence grade 3+ was 2% for GU and 0% for GI toxicity in pre-treatment symptom-free patients, and not worsened by nodal treatment. CONCLUSION: Dose escalation with hypofractionated proton boost was as effective as reported with high dose-rate brachytherapy boost, and the GU and GI toxicity profile was very similar. The proton boost was also appropriate for patients with larger prostate volume, higher T-stage, and high-risk disease encompassing elective regional node photon therapy.

The relationship between radiation doses to coronary arteries and location of coronary stenosis requiring intervention in breast cancer survivors.

BACKGROUND: To assess the relationship between radiation doses to the coronary arteries (CAs) and location of a coronary stenosis that required intervention after three-dimensional conformal radiotherapy (3DCRT) for breast cancer (BC). METHODS: The study population consisted of 182 women treated for BC in Sweden between 1992 and 2012. All women received 3DCRT and subsequently underwent coronary angiography due to a suspected coronary event. CA segments were delineated in the patient's original planning-CT and radiation doses were recalculated based on the dose distribution of the original radiotherapy (RT) plan. The location of the CA stenosis that required intervention was identified from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Logistic regression analysis was used to assess the relationship between CA radiation doses and risk of a later coronary intervention at this specific location. RESULTS: The odds ratio (OR) varied by radiation dose to the mid left anterior descending artery (LAD) (p = 0.005). Women receiving mean doses of 1-5 Gray (Gy) to the mid LAD had an adjusted OR of 0.90 (95% CI 0.47-1.74) for a later coronary intervention compared to women receiving mean doses of 0-1 Gy to the mid LAD. In women receiving mean doses of 5-20 Gy to the mid LAD, an adjusted OR of 1.24 (95% CI 0.52-2.95) was observed, which increased to an OR of 5.23 (95% CI 2.01-13.6) for mean doses over 20 Gy, when compared to women receiving mean doses of 0-1 Gy to the mid LAD. CONCLUSIONS: In women receiving conventional 3DCRT for BC between 1992 and 2012, radiation doses to the LAD remained high and were associated with an increased requirement of coronary intervention in mid LAD. The results support that the LAD radiation dose should be considered in RT treatment planning and that the dose should be kept as low as possible. Minimising the dose to LAD is expected to diminish the risk of later radiation-induced stenosis.

Initial experience with introducing national guidelines for CT- and MRI-based delineation of organs at risk in radiotherapy.

A fundamental problem in radiotherapy is the variation of organ at risk (OAR) volumes. Here we present our initial experience in engaging a large Radiation Oncology (RO) community to agree on national guidelines for OAR delineations. Our project builds on associated standardization initiatives and invites professionals from all radiotherapy departments nationwide. Presently, one guideline (rectum) has successfully been agreed on by a majority vote. Reaching out to all relevant parties in a timely manner and motivating funding agencies to support the work represented early challenges. Population-based data and a scalable methodological approach are major strengths of the proposed strategy.

Reproducibility of heart and thoracic wall position in repeated deep inspiration breath holds for radiotherapy of left-sided breast cancer patients.

BACKGROUND: Deep inspiration breath hold (DIBH) for radiotherapy of left-sided breast cancer patients can effectively move the heart away from the target and reduce the heart dose compared to treatments in free breathing. This study aims to investigate the positional reproducibility of heart edge (HE) and thoracic wall (TW) during repeated DIBHs. MATERIAL AND METHODS: At three occasions, 11 left-sided breast cancer patients were CT imaged during 6 minutes of repeated DIBHs with 60 cine CT series. The series were evenly distributed over three bed positions and for each bed position, the heart edge associated maximum heart distance (MHD) and thoracic wall-associated maximum lung distance (MLD) from a reference line were retrospectively analyzed. The high temporal resolution of the CT series enabled intrinsic heart movements to be resolved from breath hold variations. A body surface laser scanning system continuously extracted the thorax height and displayed it in a pair of goggles for patient feedback. To check for 'fake-breathing' movements, e.g. that the patient lifts its back from the couch to reach DIBH, the couch-to-spine distance was also measured in all CT series. RESULTS: The analysis was done for 1432 cine CTs captured during 292 breath holds. The DIBH moved the heart on average 15 mm in medial direction compared with free breathing. For the three bed positions studied, the mean value of the max range, across all patients, was between 11-13 mm for the MHD and 4-8 mm for the MLD. The MHD variation due to breath hold variation was twice as large as the MHD variation due to intrinsic heart movement. The couch-to-spine distance varied less than 3 mm for all fractions, i.e., no fake-breathing was discovered. CONCLUSIONS: The heart edge and thoracic wall reproducibility was high in relation to the medial heart displacement induced by the DIBH.

Hypofractionated high-energy proton-beam irradiation is an alternative treatment for WHO grade I meningiomas.

BACKGROUND: Radiation treatment is commonly employed in the treatment of meningiomas. The aim of this study was to evaluate the effectiveness and safety of hypofractionated high-energy proton therapy as adjuvant or primary treatment for WHO grade I meningiomas. METHOD: A total of 170 patients who received irradiation with protons for grade I meningiomas between 1994 and 2007 were included in the study. The majority of the tumours were located at the skull base (n = 155). Eighty-four patients were treated post subtotal resection, 42 at tumour relapse and 44 with upfront radiotherapy after diagnosis based on the typical radiological image. Irradiation was given in a hypofractionated fashion (3-8 fractions, usually 5 or 6 Gy) with a mean dose of 21.9 Gy (range, 14-46 Gy). All patients were planned for follow-up with clinical controls and magnetic resonance imaging scans at 6 months and 1, 2, 3, 5, 7 and 10 years after treatment. The median follow-up time was 84 months. Age, gender, tumour location, Simpson resection grade and target volume were assessed as possible prognostic factors for post-irradiation tumour progression and radiation related complications. RESULTS: The actuarial 5- and 10-year progression-free survival rates were 93% and 85% respectively. Overall mortality rate was 13.5%, while disease-specific mortality was 1.7% (3/170 patients). Older patients and patients with tumours located in the middle cranial fossa had a lower risk for tumour progression. Radiation-related complications were seen in 16 patients (9.4%), with pituitary insufficiency being the most common. Tumour location in the anterior cranial fossa was the only factor that significantly increased the risk of complications. CONCLUSIONS: Hypofractionated proton-beam radiation therapy may be used particularly in the treatment of larger World Health Organisation grade I meningiomas not amenable to total surgical resection. Treatment is associated with high rates of long-term tumour growth control and acceptable risk for complications.

Magnetic Resonance Compatibility of a Transponder Aimed for Radiotherapy Positioning - A Phantom Study.

BACKGROUND/AIM: Electromagnetic Positioning Systems (EMP) is a new position-ing technique in four-dimensional radiotherapy. Patients with implanted transponders may be referred for magnetic resonance imaging (MRI) making it important to establish the MR safety. MATERIALS AND METHODS: Oranges were prepared with transponders and imaged on a 3T MR scanner with different sequences. Computed tomography (CT) was performed as comparison. MR artifacts were assessed. An estimation of the maximum transponder de-flection force and heating was made. RESULTS: The mean measured displacement of transponders was 0.1 mm (range=0.03-0.3 mm). Artifacts were observed adjacent to transponders using all sequences. The deflection force on the transponder in the gantry was less than 38 mN. No heating was observed. CONCLUSION: The absence of any substantial movement, the weak measured deflection force and absence of observed heating speaks for the safe use of MR imaging with transponder 3T. Local artefacts makes evaluation impossible adjacent to transponders.

Neurovascular Bundle Infiltration Can Explain Local Relapses Using Conformal Radiotherapy of Prostate Cancer.

AIM: To quantify the impact of decreased margins for two treatment techniques, three-dimensional conformal radiotherapy (3D-CRT) and volumetric-modulated arc therapy (VMAT), on local control in curative treatment of prostate cancer. MATERIALS AND METHODS: The planning target volume (PTV) margins were decreased in steps of 1 mm from 10 to 1 mm. Treatment plans using 3D-CRT and VMAT technique were produced for all margin sizes and the dose to the neuro vascular bundles (NVB), that was not included in the PTV, was investigated. RESULTS: Due to the more conformal dose delivery using VMAT, the dose to the NVB decreased more rapidly by VMAT compared to the 3D-CRT plans. The dose difference was significant for margins from 1-7 mm. CONCLUSION: One should be very cautious before clinical routines are changed, bearing in mind whether the change means more conformal treatment technique, smaller margins or target segmentation in different imaging modalities.

Radiation dose distribution in coronary arteries in breast cancer radiotherapy.

BACKGROUND: Women irradiated for left-sided breast cancer (BC) have an increased risk of coronary artery disease compared to women with right-sided BC. We describe the distribution of radiation dose in segments of coronary arteries in women receiving adjuvant radiotherapy (RT) for left- or right-sided BC. MATERIAL AND METHODS: Fifteen women with BC, seven left-sided and eight right-sided, who had received three-dimensional conformal radiotherapy (3DCRT), constituted the study base. The heart and the segments of the coronary arteries were defined as separate organs at risk (OAR), and the mean and maximum radiation doses were calculated for each OAR. RESULTS: In women with left-sided BC, irrespective of if regional lymph node RT was given or not, maximum dose in mid and distal left anterior descending artery (mdLAD) was approximately 50 Gy in 6/7 patients, whereas women with right-sided BC mainly received low doses of radiation. In women with left-sided BC, 6/7 patients had substantially higher mean dose to the distal LAD than to the heart, ranging from 30 to 55 Gy and 3 to13 Gy, respectively. CONCLUSION: We found a pronounced difference of radiation dose distribution in the coronary arteries between women with left- and right-sided BC. Women with left-sided BC had almost full treatment dose in parts of mdLAD, regardless of if regional lymph node irradiation was given or not, while women with right-sided BC mainly received low doses to the coronary arteries.

Positive correlation between occlusion rate and nidus size of proton beam treated brain arteriovenous malformations (AVMs).

BACKGROUND: Proton beam radiotherapy of arteriovenous malformations (AVM) in the brain has been performed in Uppsala since 1991. An earlier study based on the first 26 patients concluded that proton beam can be used for treating large and medium sized AVMs that were considered difficult to treat with photons due to the risk of side effects. In the present study we analyzed the result from treating the subsequent 65 patients. MATERIAL AND METHODS: A retrospective review of the patients' medical records, treatment protocols and radiological results was done. Information about gender, age, presenting symptoms, clinical course, the size of AVM nidus and rate of occlusion was collected. Outcome parameters were the occlusion of the AVM, clinical outcome and side effects. RESULTS: The rate of total occlusion was overall 68%. For target volume 0-2 cm(3) it was 77%, for 3-10 cm(3) 80%, for 11-15 cm(3) 50% and for 16-51 cm(3) 20%. Those with total regress of the AVM had significantly smaller target volumes (p < 0.009) higher fraction dose (p < 0.001) as well as total dose (p < 0.004) compared to the rest. The target volume was an independent predictor of total occlusion (p = 0.03). There was no difference between those with and without total occlusion regarding mean age, gender distribution or symptoms at diagnosis. Forty-one patients developed a mild radiation-induced brain edema and this was more common in those that had total occlusion of the AVM. Two patients had brain hemorrhages after treatment. One of these had no effect and the other only partial occlusion from proton beams. Two thirds of those presenting with seizures reported an improved seizure situation after treatment. CONCLUSION: Our observations agree with earlier results and show that proton beam irradiation is a treatment alternative for brain AVMs since it has a high occlusion rate even in larger AVMs.

Radical prostatectomy versus high-dose irradiation in localized/locally advanced prostate cancer: A Swedish multicenter randomized trial with patient-reported outcomes.

BACKGROUND: Treatment of localized prostate cancer (PC) is controversial. This is the first randomized study comparing an open surgery procedure (radical prostatectomy) with a combination of high-dose rate brachytherapy (2×10 Gy) and external beam radiotherapy (25×2 Gy) in PC patients in Sweden 1996-2001. The two randomization arms were compared regarding differences in patients-reported outcomes, such as complications and health-related quality of life (HRQoL). MATERIAL AND METHODS: The patients had localized/locally advanced PC, clinical category T1b-T3a, N0, M0 and PSA≤50 ng/ml. All underwent total androgen blockade (six months). Self-reported HRQoL and symptoms including urinary, bowel, and sexual side effects were investigated prospectively before randomization and 12 and 24 months after randomization. A total of 89 patients were randomized and completed the EORTC QLQ C-33 and EORTC PR-25 questionnaires. RESULTS: Over the study period, there were no discernible differences in HRQoL, or complications between the two groups. Emotional functioning, however, improved statistically significantly over time, whereas Social functioning decreased, and financial difficulties increased. No statistically significant differences in group-by-time interactions were found. The survival rate was 76%. Only eight patients (9%) died of PC. CONCLUSION: Open radical prostatectomy and the combined high-dose rate brachytherapy with external beam radiation appeared to be comparable in the measured outcomes. It was not possible to draw any conclusion on the efficacy of the two treatments due to insufficient power of the study.

A comparison of patient position displacements from body surface laser scanning and cone beam CT bone registrations for radiotherapy of pelvic targets.

BACKGROUND AND PURPOSE: Optical surface detection has attractive features as a mean in radiotherapy for patient positioning tasks such as set-up, monitoring and gating. To aid in hitting radiotherapy targets the correlation between detected surface displacements and internal structure displacements is crucial. In this study, we compare set-up displacements derived from a body surface laser scanning (BSLS) system to displacements derived from bone registrations with a cone beam computed tomography (CBCT) system in order to quantify the accuracy and applicability of BSLS for fractionated treatments in the pelvic region. MATERIAL AND METHODS: Displacements from concurrent BSLS and CBCT registrations were compared for 40 patients treated in the pelvic region for a total of 170 set-ups. Surface data captured by BSLS at the first treatment fraction (BSLSref) was used as main reference for the BSLS system, while bony structures from the planning CT were used as a reference for the CBCT method. As comparison, the patient outline extracted from the planning CT was used as BSLS reference (CTref). The displacements detected by the CBCT system (skin-marks-only) was also used for comparison. RESULTS: The mean differences (± 1 SD) between the BSLS and CBCT displacements were -0.01 (± 0.17) cm, 0.00 (± 0.21) cm and 0.01 (± 0.17) cm in the lateral, longitudinal and vertical directions, respectively. The median length of the difference was 0.26 cm (0.24-0.29 cm, 95% CI). The median of the difference between CBCT and BSLS displacements based on CTref was 0.37 cm (0.30-0.39 cm) and the median for skin-marks-only was 0.38 cm (0.34-0.42 cm). CONCLUSIONS: The BSLS system is a good supplement to the CBCT system for accurate set-up for fractions when no CBCT is deemed necessary for pelvic targets. Inter-fractional skin movement in relation to bone was estimated to be 0.2 cm in the lateral (X), longitudinal (Y) and vertical direction (Z), respectively.

Integrated peripheral boost in preoperative radiotherapy for the locally most advanced non-resectable rectal cancer patients.

BACKGROUND AND PURPOSE: Few studies have explored the potential clinical advantages of dose escalation and integrated boosts for patients with non-resectable locally advanced rectal cancer. The possibility of escalating dose to non-resectable regions in these patients was the aim of this study. PATIENTS AND METHODS: Seven patients with locally very advanced rectal tumours (sacrum overgrowth or growth into pelvic side walls) were evaluated. Intensity modulated photon and pencil beam scanning proton plans with simultaneously integrated boosts (45 Gy to elective lymph nodes, 50 Gy to tumour and 62.5 Gy to boost area in 25 fractions) were compared. RESULTS: Target coverage was achieved with both photon and proton plans. Estimated risks of acute side effects put the two patients with the largest tumours at unacceptable risk for intestinal toxicity, regardless of modality. The remaining five patients had beneficial sparing of dose to the small intestine with protons. CONCLUSIONS: Adding boost to areas where rectal tumours infiltrate adjacent non-resectable organs is an attractive option which appears possible using both photon and proton irradiation. Proton plans reduced dose to organs at risk. Integrated peripheral boosts should be considered more frequently in these very advanced tumours.

Hypofractionated proton boost combined with external beam radiotherapy for treatment of localized prostate cancer.

Proton boost of 20 Gy in daily 5 Gy fractions followed by external beam radiotherapy (EBRT) of 50 Gy in daily 2 Gy fractions were given to 278 patients with prostate cancer with T1b to T4N0M0 disease. Fifty-three percent of the patients received neoadjuvant androgen deprivation therapy (N-ADT). The medium followup was 57 months. The 5-year PSA progression-free survival was 100%, 95%, and 74% for low-, intermediate-, and high-risk patients, respectively. The toxicity evaluation was supported by a patient-reported questionnaire before every consultant visit. Cumulative probability and actuarial prevalence of genitourinary (GU) and gastrointestinal (GI) toxicities are presented according to the RTOG classification. N-ADT did not influence curability. Mild pretreatment GU-symptoms were found to be a strong predictive factor for GU-toxicity attributable to treatment. The actuarial prevalence declined over 3 to 5 years for both GU and GI toxicities, indicating slow resolution of epithelial damage to the genitourinary and gastrointestinal tract. Bladder toxicities rather than gastrointestinal toxicities seem to be dose limiting. More than 5-year followup is necessary to reveal any sign of true progressive late side effects of the given treatment. Hypofractionated proton-boost combined with EBRT is associated with excellent curability of localized PC and acceptable frequencies of treatment toxicity.

A method to separate the rectum from the prostate during proton beam radiotherapy of prostate cancer patients.

UNLABELLED: The use of protons for curative treatment of prostate cancer is increasing, either as a single treatment modality or in combination with conventional radiotherapy. The proximity between prostate (target) and rectum (organ at risk) often leads to a compromise between dose to target and organ at risk. MATERIAL AND METHODS: The present study describes a method where the distance between prostate and rectum is increased by retraction of the rectum in dorsal direction. Comparative treatment plans with and without retraction of the rectum in the same patients have been studied. Nine patients with biopsy proven, localised adenocarcinoma of the prostate were studied. A cylindrical rod of Perspex was inserted into the rectum. This device allows the rectum to be retracted posteriorly. The patients were given a proton boost of 20 Gy in four fractions of 5 Gy in addition to a conventional photon beam treatment to a dose of 50 Gy in 25 fractions of 2 Gy. RESULTS: Comparative treatment planning shows that the treatment plan with rectal retraction significantly reduces (p<0.01) the volume of the rectal wall receiving high doses (equal to 70 Gy in 2 Gy fractions) in all patients. CONCLUSIONS: The proton boost treatment with retraction of rectum during treatment decreases the rectal dose substantially. This is expected to reduce rectal side effects.

Determination of aromatic hydrocarbons in bituminous emulsion sealants using headspace solid-phase microextraction and gas chromatography-mass spectrometry.

The possibility of quantitative determination of aromatic hydrocarbons in bituminous emulsion sealants was investigated using headspace solid-phase microextraction (HS-SPME) followed by gas chromatography-mass spectrometry (GC-MS). The target analytes studied were benzene, toluene, ethylbenzene, p-, m-, and o-xylene (BTEX) as well as 1,3,5- and 1,2,4-trimethylbenzene. Experimental factors influencing HS-SPME efficiency were studied (sample-headspace equilibration time, extraction time and sample matrix effects). A HS-SPME method using surrogate matrix was developed. The detection limit was estimated as approximately 0.1 ppmw for the target analytes investigated. Good linearity was observed (R(2)>0.997) for all calibration curves obtained. The repeatability of the method (RSD, relative standard deviation) was found less than 10%. The accuracy of the method given by recovery of spiked samples was between 99 and 116%. The HS-SPME method developed was applied to two commercially available bituminous emulsion sealants. External calibration and standard addition approaches were investigated, and statistical paired t-test was performed. The contents of target aromatic hydrocarbons in the sealants studied varied from approximately 0.4 to 150 ppmw. The method developed shows potential as a tool for the determination of aromatic hydrocarbons in emulsified bituminous materials.