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Lei Xing

Publications and source records attributed to Lei Xing.

At least 19 recordsLinked to original sources
PubMed2026

Leveraging Interradiomic Feature Relationships for Enhanced Prediction of Distant Metastasis and Characterization of Heterogeneity in Head and Neck Cancer.

PURPOSE: Distant metastasis remains a major cause of treatment failure in head and neck (HN) cancer, highlighting the need for more accurate early risk stratification. This study developed and validated a deep radiomics framework to characterize tumor heterogeneity from pretreatment computed tomography (CT) images and improve prediction of distant metastasis-free survival (DMFS). METHODS AND MATERIALS: This multicenter study included 3421 patients with HN cancer from 4 cohorts across 12 institutions. Radiomics features were extracted from primary tumors and transformed into OmicsMaps, a structured representation that spatially organizes interfeature relationships to facilitate learning of complex prognostic patterns. A convolutional neural network was trained to derive prognostic signatures, which were integrated with key clinical variables to construct an OmicsMap-clinical fusion model for patient risk stratification. Model performance was assessed using the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) in the CT Images from Large Head and Neck Cohort (RADCURE), HEAD-NECK-RADIOMICS-HN1 (HN1), and Head-Neck-Positron Emission Tomography-Computed Tomography (HN-PET-CT) cohorts. Radiogenomic analyses using RNA-seq data were conducted in the Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) cohort to investigate biological characteristics associated with the imaging-defined risk groups. RESULTS: The OmicsMap achieved C-index values of 0.742, 0.768, and 0.671 in the RADCURE, HN1, and HN-PET-CT cohorts, outperforming the conventional radiomics approach by 5.40%-6.37%. Incorporating clinical variables further improved generalizability, yielding a C-index of 0.864 (HN1) and 0.730 (HN-PET-CT), with time-dependent AUC of 0.727-0.895. The fusion model consistently stratified patients into distinct high- and low-risk groups for both DMFS and overall survival across cohorts (P <.01). Radiogenomic analyses revealed enrichment of immune-related pathways in the low-risk group, whereas the high-risk group exhibited a more aggressive phenotype enriched for proliferation, hypoxia, and epithelial-mesenchymal transition pathways, along with a fibrosis-prone tumor microenvironment characterized by extracellular matrix remodeling. CONCLUSIONS: Modeling interradiomic feature relationships using the OmicsMap representation substantially improves CT-based prediction of DMFS and characterization of tumor heterogeneity in HN cancer, supporting precision risk stratification in clinical oncology.

Journal Article↗
PubMed2026

Perturbation of genes linked to common schizophrenia risk variants identifies cilia programs.

Schizophrenia (SCZ) is a common psychiatric disorder characterized by psychosis, emotional withdrawal, and cognitive deficits. Most SCZ risk variants reside in non-coding regions of the genome and are thought to influence disease risk by modulating gene regulation. However, the target genes, biological pathways, and cell types through which these variants exert their effects remain poorly understood. To address this gap, we employed in vivo CRISPR droplet sequencing (CROP-seq) in the postnatal mouse neocortex. We perturbed 12 SCZ risk genes previously linked to functionally validated risk variants, followed by single-cell RNA sequencing. We identified 3,031 differentially expressed genes (DEGs) that recapitulate transcriptional alterations observed in postmortem SCZ brains. Integrative analysis using DEG clustering, factor analysis, and gene regulatory network inference uncovered convergent gene programs with distinct biological functions and cell type specificity. Notably, ciliary transcriptional programs consistently emerged across analytical frameworks. The primary cilium is a neurocircuit modulating signaling organelle in neurons and glia that remains understudied in SCZ. Perturbation of key contributors to the ciliary transcriptional programs led to significant alterations in ciliary structure, suggesting that SCZ genetic risk factors may influence how brain cells sense and transduce extracellular signals through synapse-independent mechanisms. Together, this study provides the first in vivo characterization of the functional consequence of common variant architecture in SCZ and implicates ciliary dysfunction as a convergent downstream mechanism.

Journal Article↗
PubMed2026

A dual-reporter mouse for therapeutic discovery in Angelman syndrome.

Angelman syndrome is a neurodevelopmental disorder caused by loss of the maternal UBE3A allele, the sole source of UBE3A in mature neurons owing to epigenetic silencing of the paternal allele. Although emerging therapies are being developed to restore UBE3A expression by activating the dormant paternal UBE3A allele, existing mouse models for such preclinical studies have limited throughput and utility, creating bottlenecks for both in vitro therapeutic screening and in vivo characterization. To address this, we developed the Ube3a-INSG dual-reporter knockin mouse, in which an IRES-Nanoluciferase-T2A-Sun1-sfGFP (INSG) cassette was inserted downstream of the endogenous Ube3a stop codon. The INSG model preserves UBE3A protein levels and function while enabling 2 complementary allele-specific readouts: Sun1-sfGFP and Nanoluciferase. We show that Sun1-sfGFP, a nuclear envelope-localized reporter, enables single-cell fluorescence analysis, whole-brain light-sheet imaging, and nuclear quantification by flow cytometry. Further, Nanoluciferase supports high-throughput luminescence assays for sensitive pharmacological profiling in cultured neurons and noninvasive in vivo bioluminescence imaging for pharmacodynamic assessment. By combining scalable screening, cellular analysis, and real-time in vivo monitoring in a single model, the Ube3a-INSG dual-reporter mouse provides a powerful platform to accelerate therapeutic development centered on UBE3A.

Animals↗
PubMed2006

Image interpolation in 4D CT using a BSpline deformable registration model.

PURPOSE: To develop a method for deriving the phase-binned four-dimensional computed tomography (4D CT) image sets through interpolation of the images acquired at some known phases. METHODS AND MATERIALS: Four-dimensional computed tomography data sets for 3 patients were acquired. For each patient, the correlation between inhale and exhale phases was studied and quantified using a BSpline deformable model. Images at an arbitrary phase were deduced by an interpolation of the deformation coefficients. The accuracy of the proposed scheme was assessed by comparing marker trajectories and by checkerboard/difference display of the interpolated and acquired images. RESULTS: The images at intermediate phases could be derived by an interpolation of the deformation field. An analysis of marker movements indicated that 3 mm accuracy is achievable by the interpolation. The subtraction of image analysis indicated a similar level of success. The proposed technique was useful also for automatically mapping the organ contours in a known phase to other phases, and for designing patient-specific margins in the presence of respiratory motion. Finally, the technique led to a 90% reduction in the acquired data, because in the BSpline model, a lattice of only a few thousand values is sufficient to describe a CT data set of 25 million pixels. CONCLUSIONS: Organ deformation can be well modeled by using a BSpline model. The proposed technique may offer useful means for radiation dose reduction, binning artifacts removal, and disk storage improvement in 4D imaging.

Algorithms↗
PubMed2006

Detection of nitric oxide in culture media and studies on nitric oxide formation by marine microalgae.

BACKGROUND: Multiple functions of nitric oxide (NO) in organisms and its special function and role in the atmosphere were investigated. In this study, marine microalga culture-medium NO concentrations were detected and studied in order to find the laws governing NO release by marine microalgae and relevant material was collected for discussion on the production mechanisms. MATERIAL/METHODS: NO concentrations in culture media of the marine microalgae Platymonas subcordiformis, Skeletonema costatum, and Gymnodinium sp. were detected and other media parameters, such as nutrients concentrations, Chl-a, alga cell density, and pH, were also measured concurrently. RESULTS: The NO concentrations in culture media of the marine microalgae Platymonas subcordiformis, Skeletonema costatum, and Gymnodinium sp. were detected and found to be about 10(-8)-10(-9) mol/l. The relationships between NO and nutrients and NO and pH were discussed. It was found that "NO" could serve as the message factor of microalga growth status. Experiments showed that factors affecting alga growth, such as trace elements, light, temperature, and salinity, all affected the culture-medium NO concentration. At the same time, an environmental stimulus could give rise to sudden NO peaks, with NO being a signal molecule of marine microalga stress response. CONCLUSIONS: These results indicated that low concentrations of NO were produced by marine phytoplankton (microalgae) under the condition of normal growth. NO is a message factor of microalga growth and is also a signal molecule of stress response.

Animals↗
PubMed2006

18F-labeled bombesin analogs for targeting GRP receptor-expressing prostate cancer.

UNLABELLED: The gastrin-releasing peptide receptor (GRPR) is found to be overexpressed in a variety of human tumors. The aim of this study was to develop 18F-labeled bombesin analogs for PET of GRPR expression in prostate cancer xenograft models. METHODS: [Lys3]Bombesin ([Lys3]BBN) and aminocaproic acid-bombesin(7-14) (Aca-BBN(7-14)) were labeled with 18F by coupling the Lys3 amino group and Aca amino group, respectively, with N-succinimidyl-4-18F-fluorobenzoate (18F-SFB) under slightly basic condition (pH 8.5). Receptor-binding affinity of FB-[Lys3]BBN and FB-Aca-BBN(7-14) was tested in PC-3 human prostate carcinoma cells. Internalization and efflux of both radiotracers were also evaluated. Tumor-targeting efficacy and in vivo kinetics of both radiotracers were examined in male athymic nude mice bearing subcutaneous PC-3 tumors by means of biodistribution and dynamic microPET imaging studies. 18F-FB-[Lys3]BBN was also tested for orthotopic PC-3 tumor delineation. Metabolic stability of 18F-FB-[Lys3]BBN was determined in mouse blood, urine, liver, kidney, and tumor homogenates at 1 h after injection. RESULTS: The typical decay-corrected radiochemical yield was about 30%-40% for both tracers, with a total reaction time of 150 +/- 20 min starting from 18F-. 18F-FB-[Lys3]BBN had moderate stability in the blood and PC-3 tumor, whereas it was degraded rapidly in the liver, kidneys, and urine. Both radiotracers exhibited rapid blood clearance. 18F-FB-[Lys3]BBN had predominant renal excretion. 18F-FB-Aca-BBN(7-14) exhibited both hepatobiliary and renal clearance. Dynamic microPET imaging studies revealed that the PC-3 tumor uptake of 18F-FB-[Lys3]BBN in PC-3 tumor was much higher than that of 18F-FB-Aca-BBN(7-14) at all time points examined (P < 0.01). The receptor specificity of 18F-FB-[Lys3]BBN in vivo was demonstrated by effective blocking of tumor uptake in the presence of [Tyr4]BBN. No obvious blockade was found in PC-3 tumor when 18F-FB-Aca-BBN(7-14) was used as radiotracer under the same condition. 18F-FB-[Lys3]BBN was also able to visualize orthotopic PC-3 tumor at early time points after tracer administration, at which time minimal urinary bladder activity was present to interfere with the receptor-mediated tumor uptake. CONCLUSION: This study demonstrates that 18F-FB-[Lys3]BBN and PET are suitable for detecting GRPR-positive prostate cancer in vivo.

Animals↗
PubMed2005

Experimental investigation of an inhomogeneous loss and its influence on multiwavelength fiber lasers.

Inhomogeneous loss generated by multimode laser linewidth broadening in an optical fiber is experimentally studied. With this mechanism, multiwavelength lasing is achieved by use of either fiber Raman gain or erbium-doped fiber gain. Through various pump powers and optical filter bandwidths, the relationship between inhomogeneous loss and the performance of a multiwavelength fiber laser is studied, and a physical explanation is provided.

Journal Article↗
PubMed2005

Dose-volume based ranking of incident beam direction and its utility in facilitating IMRT beam placement.

PURPOSE: Beam orientation optimization in intensity-modulated radiation therapy (IMRT) is computationally intensive, and various single beam ranking techniques have been proposed to reduce the search space. Up to this point, none of the existing ranking techniques considers the clinically important dose-volume effects of the involved structures, which may lead to clinically irrelevant angular ranking. The purpose of this work is to develop a clinically sensible angular ranking model with incorporation of dose-volume effects and to show its utility for IMRT beam placement. METHODS AND MATERIALS: The general consideration in constructing this angular ranking function is that a beamlet/beam is preferable if it can deliver a higher dose to the target without exceeding the tolerance of the sensitive structures located on the path of the beamlet/beam. In the previously proposed dose-based approach, the beamlets are treated independently and, to compute the maximally deliverable dose to the target volume, the intensity of each beamlet is pushed to its maximum intensity without considering the values of other beamlets. When volumetric structures are involved, the complication arises from the fact that there are numerous dose distributions corresponding to the same dose-volume tolerance. In this situation, the beamlets are not independent and an optimization algorithm is required to find the intensity profile that delivers the maximum target dose while satisfying the volumetric constraints. In this study, the behavior of a volumetric organ was modeled by using the equivalent uniform dose (EUD). A constrained sequential quadratic programming algorithm (CFSQP) was used to find the beam profile that delivers the maximum dose to the target volume without violating the EUD constraint or constraints. To assess the utility of the proposed technique, we planned a head-and-neck and abdominal case with and without the guidance of the angular ranking information. The qualities of the two types of IMRT plans were compared quantitatively. RESULTS: An effective angular ranking model with consideration of volumetric effect has been developed. It is shown that the previously reported dose-based angular ranking represents a special case of the general formalism proposed here. Application of the technique to a abdominal and a head-and-neck IMRT case indicated that the proposed technique is capable of producing clinically sensible angular ranking. In both cases, we found that the IMRT plans obtained under the guidance of EUD-based angular ranking were improved in comparison with that obtained using the conventional uniformly spaced beams. CONCLUSIONS: The EUD-based function is a general approach for angular ranking and allows us to identify the potentially good and bad angles for clinically complicated cases. The ranking can be used either as a guidance to facilitate the manual beam placement or as prior information to speed up the computer search for the optimal beam configuration. Thus the proposed technique should have positive clinical impact in facilitating the IMRT planning process.

Abdominal Neoplasms↗
PubMed2005

Narrow band deformable registration of prostate magnetic resonance imaging, magnetic resonance spectroscopic imaging, and computed tomography studies.

PURPOSE: Endorectal (ER) coil-based magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI) is often used to obtain anatomic and metabolic images of the prostate and to accurately identify and assess the intraprostatic lesions. Recent advancements in high-field (3 Tesla or above) MR techniques affords significantly enhanced signal-to-noise ratio and makes it possible to obtain high-quality MRI data. In reality, the use of rigid or inflatable endorectal probes deforms the shape of the prostate gland, and the images so obtained are not directly usable in radiation therapy planning. The purpose of this work is to apply a narrow band deformable registration model to faithfully map the acquired information from the ER-based MRI/MRSI onto treatment planning computed tomography (CT) images. METHODS AND MATERIALS: A narrow band registration, which is a hybrid method combining the advantages of pixel-based and distance-based registration techniques, was used to directly register ER-based MRI/MRSI with CT. The normalized correlation between the two input images for registration was used as the metric, and the calculation was restricted to those points contained in the narrow bands around the user-delineated structures. The narrow band method is inherently efficient because of the use of a priori information of the meaningful contour data. The registration was performed in two steps. First, the two input images were grossly aligned using a rigid registration. The detailed mapping was then modeled by free form deformations based on B-spline. The limited memory Broyden-Fletcher-Goldfarb-Shanno algorithm (L-BFGS), which is known for its superior performance in dealing with high-dimensionality problems, was implemented to optimize the metric function. The convergence behavior of the algorithm was studied by self-registering an MR image with 100 randomly initiated relative positions. To evaluate the performance of the algorithm, an MR image was intentionally distorted, and an attempt was then made to register the distorted image with the original one. The ability of the algorithm to recover the original image was assessed using a checkerboard graph. The mapping of ER-based MRI onto treatment planning CT images was carried out for two clinical cases, and the performance of the registration was evaluated. RESULTS: A narrow band deformable image registration algorithm has been implemented for direct registration of ER-based prostate MRI/MRSI and CT studies. The convergence of the algorithm was confirmed by starting the registration experiment from more than 100 different initial conditions. It was shown that the technique can restore an MR image from intentionally introduced deformations with an accuracy of approximately 2 mm. Application of the technique to two clinical prostate MRI/CT registrations indicated that it is capable of producing clinically sensible mapping. The whole registration procedure for a complete three-dimensional study (containing 256 x 256 x 64 voxels) took less than 15 min on a standard personal computer, and the convergence was usually achieved in fewer than 100 iterations. CONCLUSIONS: A deformable image registration procedure suitable for mapping ER-based MRI data onto planning CT images was presented. Both hypothetical tests and patient studies have indicated that the registration is reliable and provides a valuable tool to integrate the ER-based MRI/MRSI information to guide prostate radiation therapy treatment.

Algorithms↗
PubMed2005

Quantitation of the a priori dosimetric capabilities of spatial points in inverse planning and its significant implication in defining IMRT solution space.

In inverse planning, the likelihood for the points in a target or sensitive structure to meet their dosimetric goals is generally heterogeneous and represents the a priori knowledge of the system once the patient and beam configuration are chosen. Because of this intrinsic heterogeneity, in some extreme cases, a region in a target may never meet the prescribed dose without seriously deteriorating the doses in other areas. Conversely, the prescription in a region may be easily met without violating the tolerance of any sensitive structure. In this work, we introduce the concept of dosimetric capability to quantify the a priori information and develop a strategy to integrate the data into the inverse planning process. An iterative algorithm is implemented to numerically compute the capability distribution on a case specific basis. A method of incorporating the capability data into inverse planning is developed by heuristically modulating the importance of the individual voxels according to the a priori capability distribution. The formalism is applied to a few specific examples to illustrate the technical details of the new inverse planning technique. Our study indicates that the dosimetric capability is a useful concept to better understand the complex inverse planning problem and an effective use of the information allows us to construct a clinically more meaningful objective function to improve IMRT dose optimization techniques.

Algorithms↗
PubMed2005

SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder in humans which results in the loss of motor neurons. It is caused by reduced levels of the survival motor neuron (SMN) protein as a result of loss or mutation of the SMN1 gene. SMN is encoded by two genes, SMN1 and SMN2, which essentially differ by a single nucleotide in exon 7. As a result, the majority of the transcript from SMN2 lacks exon 7 (SMNDelta7). SMNDelta7 may be toxic and detrimental in SMA, which, if true, could lead to adverse effects with drugs that stimulate expression of SMN2. To determine the role of SMNDelta7 in SMA, we created transgenic mice expressing SMNDelta7 and crossed them onto a severe SMA background. We found that the SMNDelta7 is not detrimental in that it extends survival of SMA mice from 5.2 to 13.3 days. Unlike mice with selective deletion of SMN exon 7 in muscle, these mice with a small amount of full-length SMN (FL-SMN) did not show a dystrophic phenotype. This indicates that low levels of FL-SMN as found in SMA patients and absence of FL-SMN in muscle tissue have different effects and raises the question of the importance of high SMN levels in muscle in the presentation of SMA. SMN and SMNDelta7 can associate with each other and we suggest that this association stabilizes SMNDelta7 protein turnover and ameliorates the SMA phenotype by increasing the amount of oligomeric SMN. The increased survival of the SMNDelta7 SMA mice we report will facilitate testing of therapies and indicates the importance of considering co-complexes of SMN and SMNDelta7 when analyzing SMN function.

Animals↗
PubMed2005

Measurement of ionizing radiation using carbon nanotube field effect transistor.

Single-walled carbon nanotubes (SWNTs) are a new class of highly promising nanomaterials for future nano-electronics. Here, we present an initial investigation of the feasibility of using SWNT field effect transistors (SWNT-FETs) formed on silicon-oxide substrates and suspended FETs for radiation dosimetry applications. Electrical measurements and atomic force microscopy (AFM) revealed the intactness of SWNT-FET devices after exposure to over 1 Gy of 6 MV therapeutic x-rays. The sensitivity of SWNT-FET devices to x-ray irradiation is elucidated by real-time dose monitoring experiments and accumulated dose reading based on threshold voltage shift. SWNT-FET devices exhibit sensitivities to x-rays that are at least comparable to or orders of magnitude higher than commercial MOSFET (metal-oxide semiconductor field effect transistor) dosimeters and could find applications as miniature dosimeters for microbeam profiling and implantation.

Electrons↗
PubMed2005

In vivo prostate magnetic resonance spectroscopic imaging using two-dimensional J-resolved PRESS at 3 T.

In vivo magnetic resonance spectroscopic imaging of the prostate using single-voxel and multivoxel two-dimensional (2D) J-resolved sequences is investigated at a main magnetic field strength of 3 T. Citrate, an important metabolite often used to aid the detection of prostate cancer in magnetic resonance spectroscopic exams, can be reliably detected along with the other metabolites using this method. We show simulations and measurements of the citrate metabolite using 2D J-resolved spectroscopy to characterize the spectral pattern. Furthermore, using spiral readout gradients, the single-voxel 2D J-resolved method is extended to provide the spatial distribution information as well all within a reasonable scan time (17 min). Phantom and in vivo data are presented to illustrate the multivoxel 2D J-resolved spiral chemical shift imaging sequence.

Choline↗
PubMed2005

cDNA cloning, sequence analysis of the porcine LIM and cysteine-rich domain 1 gene.

LIM domain proteins are important regulators in cell growth, cell fate determination, cell differentiation and remodeling of the cell cytoskeleton by their interaction with various structural proteins, kinases and transcriptional regulators. Using molecular biology combined with in silico cloning, we have cloned the complete coding sequence of pig LIM and the cysteine-rich domain 1 gene (LMCD1) which encodes a 363 amino acid protein. The estimated molecular weight of the LMCD1 protein is 40,788 Da with a pI of 8.39. It was found to be highly expressed in both skeletal muscle and cardiac muscle. Alignment analysis revealed that the deduced protein sequence shares 86%, 91% and 93% homology with that of its human, mouse and rat counterparts, respectively. The LMCD1 protein was predicted by bioinformatics software to contain a novel cysteine-rich domain in the N-terminal region, two LIM domains in the C-terminal region, nine potential protein kinase C phosphorylation sites, seven casein kinase II phosphorylation sites, a tyrosine kinase phosphorylation site, seven N-glycosylation and N-myristoylation sites and a single potential N-glycosylation site, which is similar to the protein's human counterpart. Phylogenetic tree was constructed by aligning the amino acid sequences of the LIM domain from different species. In addition, four base mutations were detected by comparing the sequences of Large White pigs with those of Chinese Meishan pigs. The G294A mutation site was confirmed by polymerase chain reaction-single-strand conformation polymorphism analysis. Its allele frequencies were studied in five pig breeds.

Amino Acid Sequence↗
PubMed2005

Investigation of using a power function as a cost function in inverse planning optimization.

The purpose of this paper is to investigate the use of a power function as a cost function in inverse planning optimization. The cost function for each structure is implemented as an exponential power function of the deviation between the resultant dose and prescribed or constrained dose. The total cost function for all structures is a summation of the cost function of every structure. When the exponents of all terms in the cost function are set to 2, the cost function becomes a classical quadratic cost function. An independent optimization module was developed and interfaced with a research treatment planning system from the University of North Carolina for dose calculation and display of results. Three clinical cases were tested for this study with various exponents set for tumor targets and sensitive structures. Treatment plans with these exponent settings were compared, using dose volume histograms. The results of our study demonstrated that using an exponent higher than 2 in the cost function for the target achieved better dose homogeneity than using an exponent of 2. An exponent higher than 2 for serial sensitive structures can effectively reduce the maximum dose. Varying the exponent from 2 to 4 resulted in the most effective changes in dose volume histograms while the change from 4 to 8 is less drastic, indicating a situation of saturation. In conclusion, using a power function with exponent greater than 2 as a cost function can effectively achieve homogeneous dose inside the target and/or minimize maximum dose to the critical structures.

Algorithms↗
PubMed2005

Towards biologically conformal radiation therapy (BCRT): selective IMRT dose escalation under the guidance of spatial biology distribution.

It is well known that the spatial biology distribution (e.g., clonogen density, radiosensitivity, tumor proliferation rate, functional importance) in most tumors and sensitive structures is heterogeneous. Recent progress in biological imaging is making the mapping of this distribution increasingly possible. The purpose of this work is to establish a theoretical framework to quantitatively incorporate the spatial biology data into intensity modulated radiation therapy (IMRT) inverse planning. In order to implement this, we first derive a general formula for determining the desired dose to each tumor voxel for a known biology distribution of the tumor based on a linear-quadratic model. The desired target dose distribution is then used as the prescription for inverse planning. An objective function with the voxel-dependent prescription is constructed with incorporation of the nonuniform dose prescription. The functional unit density distribution in a sensitive structure is also considered phenomenologically when constructing the objective function. Two cases with different hypothetical biology distributions are used to illustrate the new inverse planning formalism. For comparison, treatments with a few uniform dose prescriptions and a simultaneous integrated boost are also planned. The biological indices, tumor control probability (TCP) and normal tissue complication probability (NTCP), are calculated for both types of plans and the superiority of the proposed technique over the conventional dose escalation scheme is demonstrated. Our calculations revealed that it is technically feasible to produce deliberately nonuniform dose distributions with consideration of biological information. Compared with the conventional dose escalation schemes, the new technique is capable of generating biologically conformal IMRT plans that significantly improve the TCP while reducing or keeping the NTCPs at their current levels. Biologically conformal radiation therapy (BCRT) incorporates patient-specific biological information and provides an outstanding opportunity for us to truly individualize radiation treatment. The proposed formalism lays a technical foundation for BCRT and allows us to maximally exploit the technical capacity of IMRT to more intelligently escalate the radiation dose.

Dose-Response Relationship, Radiation↗
PubMed2005

Optimization of radiotherapy dose-time fractionation with consideration of tumor specific biology.

The "four Rs" of radiobiology play an important role in the design of radiation therapy treatment protocol. The purpose of this work is to explore their influence on external beam radiotherapy for fast and slowly proliferating tumors and develop an optimization framework for tumor-biology specific dose-time-fractionation scheme. The linear quadratic model is used to describe radiation response of tumor, in which the time dependence of sublethal damage repair and the redistribution and reoxygenation effects are included. The optimum radiotherapeutic strategy is defined as the treatment scheme that maximizes tumor biologically effective dose (BED) while keeping normal tissue BED constant. The influence of different model parameters on total dose, overall treatment time, fraction size, and intervals is also studied. The results showed that, for fast proliferating tumors, the optimum overall time is similar to the assumed kickoff time T(k) and almost independent of interval patterns. Significant increase in tumor control can be achieved using accelerated schemes for the tumors with doubling time smaller than 3 days, but little is gained for those with doubling time greater than 5 days. The incomplete repair of normal tissues between two consecutive fractions in standard fractionation has almost no influence on the fractional doses, even for the hyperfractionation with an interval time of 8 h. However, when the resensitization effect is included, the fractional doses at the beginning and end of each irradiated week become obviously higher than others in the optimum scheme and the hyperfractionation scheme has little advantage over the standard or hypofractionation one. For slowly proliferating tumors, provided that the alpha/beta ratio of the tumor is comparable to that of the normal tissues, a hypofractionation is more favorable. The overall treatment time should be larger than a minimum, which is predominantly determined by the resensitization time. The proposed technique provides a useful tool to systematically optimize radiotherapy for fast and slow proliferating tumors and sheds important insight into the complex problem of dose-time fractionation.

Biophysical Phenomena↗