Search

We propose a fuzzy analytic hierarchy process (AHP)-based risk priority number (RPN) method in failure modes and effects analysis (FMEA) to overcome the shortcomings of traditional RPN-based FMEA. Our research group has previously published the FMEA to mitigate the failure modes (FMs) for the commissioning process of a ring gantry LINAC. However, inter-relationships among FMs were observed in high ranked FMs due to a heavy reliance on imaging system.Fuzzy AHP was applied to determine relative weights of risk impacts based on inter-relationships among FMs. Since the time sequence dependency is a major factor for risk factors, a hierarchical structure of AHP was used to reflect the directional impacts such as causal influence and feedback loop. Two fuzzy weighted RPNs, called (RPNThe differences between the two fuzzy RPN rankings are due to inherent fuzzy uncertainty and deviations in O, S, and D values submitted by the evaluators. Considering all results of traditional and fuzzy-based FMEA, the two most highly ranked FMs were identified: errors in determining the non-isocentric SSD and SSD from MV images because of the unique features of the ring gantry LINAC.This study has demonstrated the feasibility of the use of a fuzzy AHP-based RPN to perform comprehensive analysis and prioritization of FMs. The risk analysis using fuzzy AHP can be improved and/or refined based on the department's specific workflow and clinical preferences taking various priority weighting approaches into account.

Pepper (Capsicum annuum) is an important vegetable crop that has been subjected to intensive breeding, resulting in limited genetic diversity, especially for sweet peppers. Previous studies have reported pepper draft genome assemblies using short read sequencing, but their capture of the extent of large structural variants (SVs), such as presence–absence variants (PAVs), inversions, and copy-number variants (CNVs) in the complex pepper genome falls short. In this study, we sequenced the genomes of representative sweet and hot pepper accessions by long-read and/or linked-read methods and advanced scaffolding technologies. First, we developed a high-quality reference genome for the sweet pepper cultivar ‘Dempsey’ and then used the reference genome to identify SVs in 11 other pepper accessions and constructed a graph-based pan-genome for pepper. We annotated an average of 42 972 gene families in each pepper accession, defining a set of 19 662 core and 23 115 non-core gene families. The new pepper pan-genome includes informative variants, 222 159 PAVs, 12 322 CNVs, and 16 032 inversions. Pan-genome analysis revealed PAVs associated with important agricultural traits, including potyvirus resistance, fruit color, pungency, and pepper fruit orientation. Comparatively, a large number of genes are affected by PAVs, which is positively correlated with the high frequency of transposable elements (TEs), indicating TEs play a key role in shaping the genomic landscape of peppers. The datasets presented herein provide a powerful new genomic resource for genetic analysis and genome-assisted breeding for pepper improvement.

Capsaicinoids, which cause a hot sensation when eaten, are uniquely present in pepper (Capsicum sp.) and are biosynthesized by combining vanillyl amine with branched fatty acids. A mutation in the gene encoding putative aminotransferase (pAMT)—the enzyme that normally biosynthesizes the capsaicinoid precursor vanillyl amine—leads instead to the biosynthesis of vanillyl alcohol, which combines with branched fatty acids to form capsinoids. Here, we report a method for increasing the capsaicinoid and capsinoid contents using quantitative trait locus (QTL) alleles involved in capsaicinoid biosynthesis in the pericarps of extremely spicy peppers. QTLs for capsinoid contents were detected on chromosome 6 and 10 using an F2 population from ‘SNU11–001’ and ‘Bhut Jolokia (BJ)’ (‘SJ’). ‘SNU11–001’ contains high capsinoid contents and ‘BJ’ contains high capsaicinoid contents in both the placenta and pericarp. These QTLs overlapped QTL regions associated with pungency in the pericarp. ‘BJ’ was crossed also with ‘Habanero’ (‘HB’), which contains capsaicinoids mainly in the placenta, and the resulting (‘HJ’) F2 and F3 offspring with ‘BJ’ genotypes were selected based on QTL markers and the pericarp pungency phenotype. Similarly, F2 and F3 offspring with high capsinoid contents in the pericarp were selected in ‘SJ’ with reference to ‘BJ’ genotypes at the QTLs. Through continuous self-pollination, ‘SJ’ and ‘BJ’ lines with high capsinoid and capsaicinoid contents, respectively, in both the placenta and pericarp were developed. This study is the first to show that lines containing high levels of capsinoids and capsaicinoids can be bred using pericarp capsaicinoid biosynthesis genes.

We investigated the feasibility of measuring daily fiducial length on cone-beam computed tomography (CBCT) images to assess the variation in daily tumor motion for pancreatic SBRT. Motion data for fifty pancreatic SBRT patients with fiducials were analyzed retrospectively to determine the tumor motion statistics. We also performed a phantom study which involved motion analysis of three gold fiducials placed around a solid target inside the Quasar Phantom as a function of variable tumor motion and breathing period. The end-exhalation CT-50 images were compared with the CBCT images acquired prior to treatment delivery on a TrueBeam STx linear accelerator. Sinusoidal tumor motion and patients’ breathing files acquired from a Varian-RPM system were used to simulate patients’ breathing patterns. The fiducial length was measured to determine its correlation with tumor motion. Patient tumor motions along the superior-inferior (SI), anterior-posterior (AP), and left-right (LR) directions were found to be 0.7 ± 0.4 cm, 0.2 ± 0.3 cm, and 0.1 ± 0.2 cm, respectively. Average breathing period was 4.3 ± 0.8 seconds. For sinusoidal and patients’ breathing patterns, a significant correlation was observed between the fiducial length and tumor motions with R2 of 0.99. However, fiducial length was found to be independent of the variation in breathing periods. This work suggests that measuring the fiducial length on daily CBCT images could provide quantitative daily tumor motion for fiducial-based pancreatic SBRT. A timely decision to modify the motion management strategy could be made prior to daily treatment delivery.

A major QTL and candidate genes controlling capsaicinoid content in the pericarp were identified by QTL-seq and RNA-seq in Capsicum chinense. Capsaicinoid biosynthesis was previously thought to be restricted to the placental tissue; however, the recent discovery of their biosynthesis in the pericarp provides new opportunities to increase the capsaicinoid content in pepper fruits. Currently, the genetic mechanisms regulating capsaicinoid biosynthesis in the pericarp remain unknown. Here, we performed quantitative trait loci (QTL) mapping and RNA sequencing (RNA-seq) to reveal the genes controlling capsaicinoid biosynthesis in the pericarp. A whole-genome sequencing-based QTL-seq strategy was employed, identifying a major QTL on chromosome 6. To validate the QTL on chromosome 6, we performed traditional QTL mapping using the same population in QTL-seq with an additional biparental population. A total of 15 QTLs for capsaicinoid content distributed on chromosomes 3, 6, and 11 were newly identified. Among these QTLs, the genetic loci on the lower arm of chromosome 6 were commonly detected in the two mapping populations, corresponding to the location of the major QTL detected using whole-genome sequencing-based QTL-seq. Our RNA-seq analysis identified candidate genes within the common QTL that were differentially expressed in the pungent and non-pungent pericarp tissues. Our results are expected to contribute to the elucidation of the regulation of capsaicinoid biosynthesis. We also demonstrated that a combination of QTL mapping and RNA-seq is helpful for refining the candidate genes of a complicated trait of interest.

Plant breeding explores genetic diversity in useful traits to develop new, high-yielding, and improved cultivars. Ethyl methane sulfonate (EMS) is a chemical widely used to induce mutations at loci that regulate economically essential traits. Additionally, it can knock out genes, facilitating efforts to elucidate gene functions through the analysis of mutant phenotypes. Here, we developed a mutant population using the small and pungent ornamental Capsicum annuum pepper &ldquo, Micro-Pep&rdquo, This accession is particularly suitable for mutation studies and molecular research due to its compact growth habit and small size. We treated 9500 seeds with 1.3% EMS and harvested 3996 M2 lines. We then selected 1300 (32.5%) independent M2 families and evaluated their phenotypes over four years. The mutants displayed phenotypic variations in plant growth, habit, leaf color and shape, and flower and fruit morphology. An experiment to optimize Targeting Induced Local Lesions IN Genomes (TILLING) in pepper detected nine EMS-induced mutations in the eIF4E gene. The M2 families developed here exhibited broad phenotypic variation and should be valuable genetic resources for functional gene analysis in pepper molecular breeding programs using reverse genetics tools, including TILLING.

Purpose The International Atomic Energy Agency (IAEA) and the American Association of Physicists in Medicine (AAPM) have jointly published a new code of practice (CoP), TRS483, for the dosimetry of small static photon fields used in external beam radiotherapy. It gave recommendations on how to perform reference dosimetry in nonstandard machine-specific reference (msr) fields and measure field output factors in small fields. The purpose of this work was to perform a dosimetric evaluation of the recommendations given in this CoP. Methods All measurements were done in a Varian TrueBeam™ STx linear accelerator. Five ionization chambers were used for beam quality measurements, four Farmer type ionization chambers for performing reference dosimetry and two diodes for performing field output factor measurements. Field output factor measurements were done for fourteen field sizes (ranging from 0.5 cm × 0.5 cm to 10 cm × 10 cm). Beam energies used were: 6 MV WFF, 6 MV FFF, 10 MV WFF, and 10 MV FFF. Where appropriate, results from this study were compared with those obtained from the recommendations given in the IAEA TRS398 CoP, AAPM TG51 and TG51 Addendum protocols. Results Beam quality measurements show that for all beam energies and for equivalent square msr field sizes ranging from 4 cm × 4 cm to 10 cm × 10 cm, agreement between calculated and measured values of TPR20,10 (10) was within 0.6%. When %dd(10,10)X was used as beam quality specifier, the agreement was found to be within 0.8%. Absorbed dose to water per unit monitor unit at the depth of maximum dose zmax in a beam of quality Q, Dw,Qzmax/MU, was determined using both %dd(10,10)X and TPR20,10 (10) as beam quality specifiers. Measured ratios of Dw,Q (zmax )/MU, determined using the two approaches, ranged between 0.999 and 1.000 for all the beam energies investigated. Comparison with TRS398, TG51 and TG51 addendum protocols show that depending on beam energy, the mean values of the ratios TRS398/TRS483, TG51/TRS483, and TG51 Addendum/TRS483 of Dw,Q (zmax )/MU determined using both approaches show excellent agreement with TRS398 CoP (to within 0.05%); agreement with TG51 and TG51 addendum was to within 0.3% for all four beam energies investigated. Field output factors, determined using the two methods recommended in the TRS483 CoP, showed excellent agreement between the two methods. For the 1 cm collimator field size, the mean value of the field output factor obtained from an average of the two detectors investigated was found to be 2% lower than the mean value of the uncorrected ratio of readings. Conclusion For beams with and without flattening filters, the values of Dw,Q (zmax )/MU obtained following the new CoP are found to be consistent with those obtained using TRS398, TG51 and TG51 addendum protocols to within 0.3%. Field output factors for small beams can be improved when the correction factors for different detectors included in TRS483 are appropriately incorporated into their dosimetry.

We established a collection of 142 Capsicum genotypes from different geographical areas of Ethiopia with the aim of capturing genetic diversity. Morphological traits and high-resolution melting analysis distinguished one Capsicum baccatum, nine Capsicum frutescens and 132 Capsicum annuum accessions in the collection. Measurement of plant growth parameters revealed variation between germplasms in parameters including plant height, stem thickness, internode length, number of side branches, fruit width, and fruit length. Broad-sense heritability was maximum for fruit weight, followed by length and width of leaves. We used genotyping by sequencing (GBS) to identify single-nucleotide polymorphisms (SNPs) in the panel of 142 Capsicum germplasms and found 2,831,791 genome-wide SNP markers. Among these, we selected 53,284 high-quality SNPs and used them to estimate the level of genetic diversity, population structure, and phylogenetic relationships. From model-based ancestry analysis, the phylogenetic tree and principal-coordinate analysis (PCoA), we identified two distinct genetic populations: one comprising 132 C. annuum accessions and the other comprising the nine C. frutescens accessions. GWAS analysis detected 509 SNP markers that were significantly associated with fruit-, stem- and leaf-related traits. This is the first comprehensive report of the analysis of genetic variation in Ethiopian Capsicum species involving a large number of accessions. The results will help breeders utilize the germplasm collection to improve existing commercial cultivars.

Pumpkins (Cucurbita moschata) are one of the most important economic crops in genus Cucurbita worldwide. They are a popular food resource and an important rootstock resource for various Cucurbitaceae. Especially, C. moschata is widely used as a rootstock for the commercial production of bloomless cucumbers in East Asia. Since the genetic diversity of the commercial rootstock varieties is narrow, there has been an increasing demand for the trait development of abiotic and biotic stress tolerance breeding. In this study, 2071 high-quality SNPs that were distributed evenly across 20 chromosomes of pumpkins were discovered through the genotyping-by-sequencing (GBS) analysis of 610 accessions of C. moschata germplasm with a global origin. Using these SNPs, various analyses of the genetic diversity and the population structure were performed. Three subgroups were clustered from the germplasm collection, which included East Asia, Africa, and America, and these areas were included the most in each subgroup. Among those groups, accessions from Africa and South Asia showed the highest genetic diversity, which was followed by the Mexico accessions. This result reflected that large gene pools that consist of various native landraces have been conserved in those of countries. Based on the genetic diversity, we finally constructed the C. moschata core collection, which included 67 representative accessions from the 610 germplasms. Five morphological traits that are important in commercial grafting and rootstock seed production, which include the cotyledon length, the cotyledon width, the hypocotyl length, the internode length, and the number of female flowers, were investigated for three years and used to confirm the validity of the core collection selection. The results are expected to provide valuable information about the genetic structure of the worldwide C. moschata germplasm and help to create new gene pools to develop genetically diverse rootstock breeding materials.

Identification of a novel pungency-controlling gene Pun3, which acts as a master regulator of capsaicinoid biosynthetic genes in Capsicum annuum. Capsaicinoid is a unique compound that gives hot peppers (Capsicum spp.) their spicy taste. The Pun1 and Pun2 loci are known to control pungency in Capsicum species. Whereas Pun1 encodes an acyltransferase, the identity of Pun2 is currently unknown. Here, we used recombinant inbred lines and F2 plants derived from a cross between the non-pungent C. annuum accession ‘YCM334’ and the pungent C. annuum cultivar ‘Tean’ to identify a novel non-pungency locus. Inheritance studies showed that non-pungency in C. annuum ‘YCM334’ is controlled by a single recessive gene, which we named Pun3. Using a high-density SNP map derived from genotyping-by-sequencing, Pun3 was mapped to chromosome 7. By comparing physical information about the Pun3 region in the C. annuum ‘Zunla-1’ and C. chinense ‘PI159236’ reference genomes, we identified candidate genes in this target region. One cDNA sequence from ‘PI159236’ was homologous to an unannotated gene in ‘Zunla-1.’ This sequence was also homologous to CaMYB31, which is expressed only in ‘Tean’ and harbors one stop codon in the non-pungent accession ‘YCM334.’ RNA-Seq analysis showed that major structural genes in the capsaicinoid biosynthetic pathway were significantly downregulated in ‘YCM334’ compared to pungent pepper. Therefore, CaMYB31 is a candidate gene for Pun3, which may act as a master regulator of capsaicinoid biosynthetic genes in pepper.

Purpose A new type of linear accelerator (linac) was recently introduced into the market by a major manufacturer. Our institution is one of the early users of this preassembled and preconfigured dual-layer multileaf collimator (MLC), ring-gantry linac - Halcyon™ (1st version). We performed a set of full acceptance testing and commissioning (ATC) measurements for three Halcyon machines and compared the measured data with the standard beam model provided by the manufacturer. The ATC measurements were performed following the guidelines given in different AAPM protocols as well as guidelines provided by the manufacturer. The purpose of the present work was to perform a risk assessment of the ATC process for this new type of linac and investigate whether the results obtained from this analysis could potentially be used as a guideline for improving the design features of this type of linac. Methods AAPM's TG100 risk assessment methodology was applied to the ATC process. The acceptance testing process relied heavily on the use of a manufacturer-supplied phantom and the automated analysis of electronic portal imaging device (EPID) images. For the commissioning process, a conventional measurement setup and process (e.g., use of water tank for scanning) was largely used. ATC was performed using guidelines recommended in various AAPM protocols (e.g., TG-106, TG-51) as well as guidelines provided by the manufacturer. Six medical physicists were involved in this study. Process maps, process steps, and failure modes (FMs) were generated for the ATC procedures. Failure modes and effects analysis (FMEA) were performed following the guidelines given in AAPM TG-100 protocol. The top 5 and top 10 highest-ranked FMs were identified for the acceptance and commissioning procedures, respectively. Quality control measures were suggested to mitigate these FMs. Results A total of 38 steps and 88 FMs were identified for the entire ATC process. Fourteen steps and 34 FMs arose from acceptance testing. The top 5 FMs that were identified could potentially be mitigated by the manufacturer. For commissioning, a total of 24 steps and 54 potential FMs were identified. The use of separate measurement tools that are not machine-integrated has been identified as a cause for the higher number of steps and FMs generated from the conventional ATC approach. More than half of the quality control measures recommended for both acceptance and commissioning could potentially be incorporated by the manufacturer in the design of the Halcyon machine. Conclusion This paper presents the results of FMEA and quality control measures to mitigate the FMs for the ATC process for Halcyon machine. Unique FMs that result from the differences in the ATC guidelines provided by the vendor and current conventional protocols, and the challenges of performing the ATC due to the new linac features and ring-gantry design were highlighted for the first time. The FMs identified in the present work along with the suggested quality control measures, could potentially be used to improve the design features of future ring-gantry type of linacs that are likely to be preassembled, preconfigured, and heavily reliant on automation and image guidance.

A retrospective review of 32 patients with stage III nonsmall cell lung cancer who underwent chemoradiation with image-guided radiotherapy (IGRT) was recorded. Acute grade 3-4 hematologic and esophageal toxicities developed in 6 and 13 patients respectively. At a median follow-up of 14.5 months, only one patient developed grade 3 pneumonitis. The median survival was estimated to be 17 months. Five patients (15%) developed loco-regional recurrences, and 17 patients (53%) distant metastases. Grade 3-4 toxicities remained significant during chemoradiation with IGRT. However, the reduced rate of severe pneumonitis despite a high tumor dose is encouraging and needs to be investigated in future prospective studies.

This work quantified differences between recommendations of the TG‐51 and TG‐51 addendum reference dosimetry protocols. Reference dosimetry was performed for flattened photon beams with nominal energies of 6, 10, 15, and 23 MV, as well as flattening‐filter free (FFF) beam energies of 6 and 10 MV, following the recommendations of both the TG‐51 and TG‐51 addendum protocols using both a Farmer® ionization chamber and a scanning ionization chamber with calibration coefficients traceable to absorbed dose‐to‐water (D w) standards. Differences in D w determined by the two protocols were 0.1%–0.3% for beam energies with a flattening filter, and up to 0.2% and 0.8% for FFF beams measured with the scanning and Farmer® ionization chambers, respectively, due to kQ determination, volume‐averaging correction, and collimator jaw setting. Combined uncertainty was between 0.91% and 1.2% (k = 1), varying by protocol and detector.

Aims and background To evaluate the effectiveness of tomotherapy-based image-guided radiotherapy (IGRT) on the radiation dose to the cochlea in patients with nasopharyngeal cancer. Methods and study design A retrospective review of five patients undergoing concurrent chemoradiation with tomotherapy for locally advanced nasopharyngeal cancer was performed. Results The mean dose to the right and left cochlea was 25 Gy and 35.3 Gy respectively, while the dose to the gross tumor ranged from 70 to 75 Gy. All patients had excellent clinical response to the treatment at a median follow-up of five months. Conclusions IGRT for head and neck cancer delivered by tomotherapy can significantly decrease the radiation dose to the cochlea without sacrificing target volume coverage.

We performed an evaluation of the CyberKnife InCise MLC by comparing plan qualities for single and multiple brain lesions generated using the first version of InCise MLC, fixed cone, and Iris collimators. We also investigated differences in delivery efficiency among the three collimators. Twenty‐four patients with single or multiple brain mets treated previously in our clinic on a CyberKnife M6 using cone/Iris collimators were selected for this study. Treatment plans were generated for all lesions using the InCise MLC. Number of monitor units, delivery time, target coverage, conformity index, and dose falloff were compared between MLC‐ and clinical cone/Iris‐based plans. Statistical analysis was performed using the nonparametric Wilcoxon‐Mann‐Whitney signed‐rank test. The planning accuracy of the MLC‐based plans was validated using chamber and film measurements. The InCise MLC‐based plans achieved mean dose and target coverage comparable to the cone/Iris‐based plans. Although the conformity indices of the MLC‐based plans were slightly higher than those of the cone/Iris‐based plans, beam delivery time for the MLC‐based plans was shorter by 30%∼40%. For smaller targets or cases with OARs located close to or abutting target volumes, MLC‐based plans provided inferior dose conformity compared to cone/Iris‐based plans. The QA results of MLC‐based plans were within 5% absolute dose difference with over 90% gamma passing rate using 2%/2 mm gamma criteria. The first version of InCise MLC could be a useful delivery modality, especially for clinical situations for which delivery time is a limiting factor or for multitarget cases. PACS number(s): 87.53.Ly, 87.55.D‐

Capsinoids have similar biological effects as capsaicinoids, including anticancer and anti-obesity properties. The Capsicum chinense ‘SNU11-001’ variety of pepper was previously reported to contain high levels of capsinoids due to a mutation in the putative aminotransferase (pAMT) gene, which leads to production of the capsinoid precursor vanillyl alcohol. Here, to develop Capsicum annuum pepper varieties with high capsinoid contents, marker-assisted backcrossing was performed during backcross breeding. For foreground selection, plants carrying the pAMT/pamt genotype were selected from BC1F1 and BC2F1 populations using SCAR markers derived from the unique pamt mutation of ‘SNU11-001.’ To obtain background selection markers, 412 single nucleotide polymorphism (SNP) markers were screened to identify SNP markers polymorphic between the ‘Shinhong’ paternal lines and ‘SNU11-001.’ Of the 412 SNP markers, 204 polymorphic SNP markers evenly distributed in pepper genome were selected. BC1F1 and BC2F1 plants carrying the pAMT/pamt genotype were subjected to background selection using these SNP markers. Multiple genotypes were analyzed using a high-throughput genotyping system. As a result, one BC1F1 plant 84 % similar to the recurrent parent and seven BC2F1 plants showing more than 96 % recovery of the recurrent parent genotype were selected. Genetic backgrounds of the selected BC2F1 plants were evaluated using the genotype-by-sequencing (GBS) method to confirm the background selection results from the SNP marker set. GBS results showed that the recovery rate and positions of introgressed segments were well matched between two methods, demonstrating MABC can be successfully performed with only ~200 SNP markers.

To investigate the ability of helical tomotherapy (HT) to spare critical organs immediately adjacent to the tumor target in stereotactic body radiation therapy (SBRT) for centrally located lung lesions.HT SBRT plans for 10 patients with centrally located lesions or lesions immediately adjacent to a critical structure were generated. A total of 70 Gy in 10 fractions was prescribed to the planning target volume (PTV) to satisfy a target volume coverage of ≥95% PTV receiving 70 Gy and an established set of dose constraints for the organs at risk (OARs). Quality assurance (QA) of the HT plans was performed with both ion chamber and film measurements.The PTV coverage criteria was met with 95% of the PTV receiving 70.68 ± 0.33 Gy for all cases even though the OARs immediately adjacent to the PTV ranged from 0.38 to 0.85 cm away. The mean lung dose (MLD), and V(20) were 7.15 ± 1.44 Gy, and 11.93 ± 3.24 % for the total lung, respectively. The dose parameters of MLD, V(5), V(10), and V(20) for the contralateral lung were significantly lower than those for the ipsilateral lung (p0.05). An average dose fall off from the PTV periphery to the edge of the immediately adjacent OAR was 47.6% over an average distance of 4.87 mm. Comparison of calculated and measured doses with the ion chamber showed an average of 1.85% point dose error, whereas an average mean gamma and the area with a gamma larger than 1 of 0.20 and 0.94% were observed, respectively.HT allows the sparing of critical structures immediately adjacent to the tumor target, thus making SBRT for these centrally located lesions feasible.

summary We would like to determine the effectiveness of image-guided radiotherapy (IGRT) to reduce laryngeal edema following treatment for head and neck cancer and to assess patient perception of voice and speech after treatment. We conducted a retrospective review of 44 patients undergoing radiation for non-laryngeal and non-hypopharyngeal head and neck cancers. Endoscopic and/or mirror examinations of the larynx were performed following radiotherapy at each follow-up visit. Laryngeal edema was assessed based on the Radiation Therapy Oncology Group grading scale. Patients were also asked to rate about the voice and speech quality relative to their pre-radiotherapy status. The mean laryngeal dose was 16.3 Gy (range: 11.7–45.5 Gy). At a median follow-up of 14 months (range: 2–31 months), three patients (7%) developed laryngeal edema (one grade 1, two grade 2). The mean laryngeal dose was respectively 20.3 Gy in two patients and 20.7 Gy in the third patient developing laryngeal edema. Except for one patient who continued to smoke and drink after radiotherapy, no patient reported any significant change in voice and speech quality after treatment. IGRT results in low rates and low severity of laryngeal edema following treatment for non-laryngeal and non-hypopharyngeal head and neck cancers and may preserve voice quality.

Introduction: Local therapy is becoming increasingly important as a part of the definitive treatment for malignant pleural mesothelioma after extrapleural pneumonectomy (EPP) because of the emergence of trimodality therapy consisted of chemotherapy, EPP, and adjuvant radiotherapy. Herein, we explore the current evidence and indications for adjuvant intensity-modulated radiotherapy (IMRT), as well as how to further improve this technique and adapt new technology in the delivering adjuvant radiotherapy in the setting of trimodality therapy. Methods: A systematic review of relevant studies identified through PubMed, ISI Web of Knowledge (Web of Science), the Cochrane Library, and the National Guideline Clearinghouse search engines was performed. Results: Local control remains poor despite the inclusion of conventional adjuvant radiation therapy in trimodality therapy. This can be improved by the delivery of adjuvant IMRT. However, IMRT can be associated with severe pulmonary toxicity if the radiation dose to the remaining lung is not kept to a very low level. This is especially true when patients are receiving chemotherapy. New advances in technology can allow for lower doses to the contralateral lung, decreased treatment delivery time, and improved target dose coverage. Conclusion: Excellent local control can be achieved through adjuvant IMRT after EPP for malignant pleural mesothelioma. Severe pulmonary toxicity may be avoided by setting stringent dose constraints for the contralateral lung. This can be aided by the advances in technology. Post-treatment surveillance may be reliably conducted by periodical [18F]-fluorodeoxyglucose-positron emission tomography imaging.

Purpose: To evaluate the robustness of TG119-based quality assurance metrics for an IMRT system. Methods: Four planners constructed treatment plans for the five IMRT test cases described in TG119. All plans were delivered to a 30 cm × 30 cm × 15 cm solid water phantom in one treatment session in order to minimize session-dependent variation from phantom setup, film quality, machine performance, etc. Composite measurements utilized film and an ionization chamber. Per-field measurements were collected using a diode array device at an effective depth of 5 cm. All data collected were analyzed using the TG119 specifications to determine the confidence limit values for each planner separately and then compared. Results: The mean variance of ion chamber measurements for each planner was within 1.7% of the planned dose. The resulting confidence limits were 3.13%, 1.98%, 3.65%, and 4.39%. Confidence limit values determined by composite film analysis were 8.06%, 13.4%, 9.30%, and 16.5%. Confidence limits from per-field measurements were 1.55%, 0.00%, 0.00%, and 2.89%. Conclusions: For a single IMRT system, the accuracy assessment provided by TG119-based quality assurance metrics showed significant variations in the confidence limits between planners across all composite and per-field evaluations. This observed variation is likely due to the different levels of modulation between each planner’s set of plans. Performing the TG119 evaluation using plans produced by a single planner may not provide an adequate estimation of IMRT system accuracy.

BACKGROUND: Image-guided radiotherapy (IGRT) combines precise target visualization with optimal delivery of radiation dose to spare normal tissue from radiation and may potentially reduce side-effects and long-term treatment complications. We have assessed the effectiveness of IGRT for locally advanced rectal cancer. METHODS: A retrospective review of 22 patients with locally advanced rectal cancer who underwent preoperative chemoradiation was conducted. RESULTS: Nineteen patients (median age, 69 years) underwent surgical resection after chemoradiation. All 19 patients achieved complete resection with negative margins. Seven patients (32%) had no residual tumor in the surgical specimen. One patient had grade 4 gastrointestinal toxicity and hematological toxicity probably related to inadvertent overdosing of capecitabine. The median survival for the whole group-patients who had pCR and those who did not have pCR-was 14, 17, and 15 months, respectively. CONCLUSIONS: Image-guided radiotherapy provided effective treatment for locally advanced rectal cancer with minimal toxicity and should be investigated in future prospective trials.

We would like to compare the effectiveness of image-guided (IGRT) and intensity-modulated (IMRT) radiotherapy to spare the larynx in head and neck cancer patients. A retrospective review of 48 patients undergoing radiation for non-laryngeal and non-hypopharyngeal head and neck cancers. Mean laryngeal and hypopharyngeal dose was compared between 11 patients treated with IMRT and 37 patients treated with IGRT. Mean laryngeal dose was, respectively, 41.2 Gy and 22.8 Gy for the IMRT and IGRT technique (p

To investigate potential dose calculation errors in the low-dose regions and identify causes of such errors for intensity-modulated radiotherapy (IMRT).The IMRT treatment plans of 23 patients with lung cancer and mesothelioma were reviewed. Of these patients, 15 had severe pulmonary complications after radiotherapy. Two commercial treatment-planning systems (TPSs) and a Monte Carlo system were used to calculate and compare dose distributions and dose-volume parameters of the target volumes and critical structures. The effect of tissue heterogeneity, multileaf collimator (MLC) modeling, beam modeling, and other factors that could contribute to the differences in IMRT dose calculations were analyzed.In the commercial TPS-generated IMRT plans, dose calculation errors primarily occurred in the low-dose regions of IMRT plans (50% of the radiation dose prescribed for the tumor). Although errors in the dose-volume histograms of the normal lung were small (5%) above 10 Gy, underestimation of dose10 Gy was found to be up to 25% in patients with mesothelioma or large target volumes. These errors were found to be caused by inadequate modeling of MLC transmission and leaf scatter in commercial TPSs. The degree of low-dose errors depends on the target volumes and the degree of intensity modulation.Secondary radiation from MLCs contributes a significant portion of low dose in IMRT plans. Dose underestimation could occur in conventional IMRT dose calculations if such low-dose radiation is not properly accounted for.

Purpose: To assess quantitatively the impact of incorporating functional lung imaging into intensity-modulated radiation therapy planning for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Sixteen patients with advanced-stage NSCLC who underwent radiotherapy were included in this study. Before radiotherapy, each patient underwent lung perfusion imaging with single-photon-emission computed tomography and X-ray computed tomography (SPECT-CT). The SPECT-CT was registered with simulation CT and was used to segment the 50- and 90-percentile hyperperfusion lung (F50 lung and F90 lung). Two IMRT plans were designed and compared in each patient: an anatomic plan using simulation CT alone and a functional plan using SPECT-CT in addition to the simulation CT. Dosimetric parameters of the two types of plans were compared in terms of tumor coverage and avoidance of normal tissues. Results: In incorporating perfusion information in IMRT planning, the median reductions in the mean doses to the F50 and F90 lung in the functional plan were 2.2 and 4.2 Gy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with >5 Gy, >10 Gy, and >20 Gy in the functional plans were 7.1%, 6.0%, and 5.1%, respectively, for F50 lung, and 11.7%, 12.0%,more » and 6.8%, respectively, for F90 lung. A greater degree of sparing of the functional lung was achieved for patients with large perfusion defects compared with those with relatively uniform perfusion distribution. Conclusion: Function-guided IMRT planning appears to be effective in preserving functional lung in locally advanced-stage NSCLC patients.« less

Because of complex dose distributions and dose gradients that are created in three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiation therapy (IMRT), photon- and electron-energy spectra might change significantly with spatial locations and doses. This study examined variations in photon- and electron-energy spectra in 3D-CRT and IMRT photon fields. The effects of spectral variations on water-to-material stopping-power ratios used in Monte Carlo treatment planning systems and the responses of energy-dependent dosimeters, such as thermoluminescent dosimeters (TLDs) and radiographic films were further studied. The EGSnrc Monte Carlo code was used to simulate megavoltage 3D-CRT and IMRT photon fields. The photon- and electron-energy spectra were calculated in 3D water phantoms and anthropomorphic phantoms based on the fluence scored in voxel grids. We then obtained the water-to-material stopping-power ratios in the local voxels using the Spencer-Attix cavity theory. Changes in the responses of films and TLDs were estimated based on the calculated local energy spectra and published data on the dosimeter energy dependency. Results showed that the photon-energy spectra strongly depended on spatial positions and doses in both the 3D-CRT and IMRT fields. The relative fraction of low-energy photons (< 100 keV) increased inversely with the photon dose in low-dose regions of the fields. A similar but smaller effect was observed for electrons in the phantoms. The maximum variation of the water-to-material stopping-power ratio over the range of calculated dose for both 3D-CRT and IMRT was negligible (< 1.0%) for ICRU tissue, cortical bone, and soft bone and less than 3.6% for dry air and lung. Because of spectral softening at low doses, radiographic films in the phantoms could over-respond to dose by more than 30%, whereas the over-response of TLDs was less than 10%. Thus, spatial variations of the photon- and electron-energy spectra should be considered as important factors in 3D-CRT and IMRT dosimetry.

Conventional radiotherapy for cervical cancer relies on clinical examination, 3-dimensional conformal radiotherapy (3D-CRT), and 2-dimensional intracavitary brachytherapy.Excellent local control and survival have been obtained for small early stage cervical cancer with definitive radiotherapy. For bulky and locally advanced disease, the addition of chemotherapy has improved the prognosis but toxicity remains significant. New imaging technology such as positron emission tomography (PET) and magnetic resonance imaging (MRI) has improved tumor delineation for radiotherapy planning. Image-guided radiotherapy (IGRT) may decrease treatment toxicity of whole pelvic radiation because of its potential for bone marrow, bowel, and bladder sparring. Tumor shrinkage during whole pelvic IGRT may optimize image-guided brachytherapy (IGBT), allowing for better local control and reduced toxicity for patients with cervical cancer. IGRT and IGBT should be integrated in future prospective studies for cervical cancer.

A multileaf collimator (MLC) model, "MATMLC," was developed to simulate MLCs for Monte Carlo (MC) dose calculations of intensity-modulated radiation therapy (IMRT). This model describes MLCs using matrices of regions, each of which can be independently defined for its material and geometry, allowing flexibility in simulating MLCs from various manufacturers. The free parameters relevant to the dose calculations with this MLC model included MLC leaf density, interleaf air gap, and leaf geometry. To commission the MLC model and its free parameters for the Varian Millennium MLC-120 (Varian Oncology Systems, Palo Alto, CA), we used the following leaf patterns: (1) MLC-blocked fields to test the effects of leaf transmission and leakage; (2) picket-fence fields to test the effects of the interleaf air gap and tongue-groove design; and (3) abutting-gap fields to test the effects of rounded leaf ends. Transmission ratios and intensity maps for these leaf patterns were calculated with various sets of modeling parameters to determine their dosimetric effects, sensitivities, and their optimal combinations to give the closest agreement with measured results. Upon commissioning the MLC model, we computed dose distributions for clinical IMRT plans using the MC system and verified the results with those from ion chamber and thermoluminescent dosimeter measurements in water phantoms and anthropomorphic phantoms. This study showed that the MLC transmission ratios were strongly dependent on both leaf density and the interleaf air gap. The effect of interleaf air gap and tongue-groove geometry can be determined most effectively through fence-type MLC patterns. Using the commissioned MLC model, we found that the calculated dose from the MC system agreed with the measured data within clinically acceptable criteria from low- to high-dose regions, showing that the model is acceptable for clinical applications.

The Monte Carlo N-Particle (MCNP) code and a set of high-temperature neutron cross-section data were used to develop an accurate three-dimensional computational model of the Texas A and M University Nuclear Science Center Reactor (NSCR) at full power. The geometry of the reactor core was modeled as closely as possible including the details of all the fuel elements and control rods. The most significant approximation was made for entrained fission products because of the lack of knowledge of fission product inventory in the current reactor core. This study used the concept of 'average fission product' to model the fission product in the reactor core and determined the concentration of the average fission product by repeating criticality calculations to make the reactor critical for a given critical condition. Finally, the developed model was tested by comparing the calculated results with those of other approaches, i.e., (a) an in-house three-dimensional diffusion code and (b) foil activation measurement. The developed reactor model showed a good agreement with these approaches. The developed model predicted the thermal neutron flux in samples within 11% of difference when compared with the results from the diffusion code and predicted the production of {sup 198}Au and {sup 60}Co withinmore » {approx}20% of difference when compared with the values measured with foils. The developed model also calculated the neutron energy spectrum very consistently with the other approaches for the entire energy range considered in this study.« less

Conclusion. IGRT delivered by tomotherapy may be ideally suited for sarcoma of the extremities because of its ability to achieve a high radiation dose along with excellent normal tissue sparing. Further prospective studies should be conducted to confirm this hypothesis. Aims and background. To evaluate the effectiveness of helical tomotherapy-based image-guided radiotherapy (IGRT) following surgery for lower extremity sarcoma. Methods and study design. A retrospective review of three patients undergoing postoperative irradiation with tomotherapy for lower extremity sarcoma was conducted. Planning target volume (PTV) coverage, acute side effects, long-term complications and functional results were assessed. Results. Tomotherapy allows adequate coverage of the PTV without an excessive radiation dose to the normal adjacent structures. Radiotherapy side effects were acceptable with no treatment breaks. All patients were disease free with no complications and no impairment of their daily activity at the last follow-up.

Background: In this study the feasibility of intensity-modulated radiotherapy (IMRT) and tomotherapy-based image-guided radiotherapy (IGRT) for locally advanced esophageal cancer was assessed. Methods: A retrospective study of ten patients with locally advanced esophageal cancer who underwent concurrent chemotherapy with IMRT (1) and IGRT (9) was conducted. The gross tumor volume was treated to a median dose of 70 Gy (62.4-75 Gy). Results: At a median follow-up of 14 months (1-39 months), three patients developed local failures, six patients developed distant metastases, and complications occurred in two patients (1 tracheoesophageal fistula, 1 esophageal stricture requiring repeated dilatations). No patients developed grade 3-4 pneumonitis or cardiac complications. Conclusions: IMRT and IGRT may be effective for the treatment of locally advanced esophageal cancer with acceptable complications.

Background: To assess the tolerance of patients with small cell lung cancer undergoing chemoradiation with tomotherapy-based image-guided radiotherapy (IGRT).Materials and methods: A retrospective review of the toxicity profile for nine patients with small cell lung cancer of the limited stage who underwent chemoradiation delivered with helical tomotherapy (HT) has been conducted.Results: Acute grade 3-4 hematologic and esophagitis toxicities developed in two and three patients respectively. One patient developed a pulmonary embolism during radiotherapy. Seven patients had weight loss ranging from 0 to 30 pounds (median: 4 pounds). Three patients had treatment breaks ranging from 2 to 12 days. At a median follow-up of 11 months (range: 2-24 months), no patients developed any radiation related toxicities such as grade 3-4 pneumonitis or other long-term complications. The median survival was estimated to be 15 months. There were 2 local recurrences, 3 mediastinal recurrences, and six distant metastases.Conclusion: Grade 3-4 toxicities remained significant during chemoradiation when radiation was delivered with tomotherapy-based IGRT. However, the absence of grade 3-4 pneumonitis is promising and the use of HT needs to be investigated in future prospective studies.