Technology in Cancer Research & Treatment

IMRT and helical tomotherapy for head and neck cancer (HNC) treatment are associated with higher doses to certain non-target tissues than traditional static beam techniques. We hypothesized that this may lead to higher acute mucosal and hematologic toxicities. This analysis was limited to 178 patients receiving >60 Gy with concurrent weekly cisplatin. Radiation delivery used 3D-CRT in 41 patients (23%), conventional IMRT in 56 patients (31%), and helical tomotherapy in 81 patients (46%). Acute mucositis rates, weekly hematologic parameters, and ability to deliver planned chemotherapy cycles were examined for each patient during their course of chemoradiotherapy. Analysis showed patients were well balanced with regard to sex, age, and stage. Treatment time, as assessed by delivered monitor units, varied significantly between the 3D-CRT (median = 502), IMRT (median = 1087), and tomotherapy (median = 6757) cohorts. Acute mucositis grades did not significantly differ between the three subsets. Through six weeks of chemoradiotherapy, the median decline in hemoglobin was 15.6%, the median decline in platelets was 30.6%, and the median decline in leukocytes was 51.5%, but these drops were not significantly different between treatment cohorts. Chemotherapy was discontinued or held secondary to hematologic toxicity in 12% of 3D-CRT patients, 5% of IMRT patients and 15% of tomotherapy patients (p = 0.14). In conclusion, HNC patients undergoing high dose radiation with concurrent weekly cisplatin chemotherapy, the longer beam-on times and larger volumes of low-to-moderate radiation doses to non-target tissues associated with modern IMRT delivery techniques do not appear to result in increased acute hematologic or mucosal toxicities.

In order to facilitate the leaf sequencing process in intensity modulated radiation therapy (IMRT), and design of a practical leaf sequencing algorithm, it is an important issue to smooth the planned fluence maps. The objective is to achieve both high-efficiency and high-precision dose delivering by considering characteristics of leaf sequencing process. The key factor which affects total number of monitor units for the leaf sequencing optimization process is the max flow value of the digraph which formulated from the fluence maps. Therefore, we believe that one strategy for compromising dose conformity and total number of monitor units in dose delivery is to balance the dose distribution function and the max flow value mentioned above. However, there are too many paths in the digraph, and we don't know the flow value of which path is the maximum. The maximum flow value among the horizontal paths was selected and used in the objective function of the fluence map optimization to formulate the model. The model is a traditional linear constrained quadratic optimization model which can be solved by interior point method easily. We believe that the smoothed maps from this model are more suitable for leaf sequencing optimization process than other smoothing models. A clinical head-neck case and a prostate case were tested and compared using our proposed model and the smoothing model which is based on the minimization of total variance. The optimization results with the same level of total number of monitor units (TNMU) show that the fluence maps obtained from our model have much better dose performance for the target/non-target region than the maps from total variance based on the smoothing model. This indicates that our model achieves better dose distribution when the algorithm suppresses the TNMU at the same level. Although we have just used the max flow value of the horizontal paths in the diagraph in the objective function, a good balance has been achieved between the dose conformity and the total number of monitor units. This idea can be extended to other fluence map optimization model, and we believe it can also achieve good performance.

The purpose of this study was to evaluate the two functions: segment weight optimization (SWO) and segment edit (SE) in the latest XiO 4.7 radiation treatment planning system and their effect on the planning of intensity modulated radiation therapy (IMRT) for Nasopharyngeal Carcinoma (NPC). SWO first appeared in XiO 4.5 and SE in XiO 4.7. Twelve patients with NPC were selected and there were three plans for each patient: the common step-and-shoot IMRT plan (C-IMRT); S-IMRT was based on the result of C-IMRT and the plan was further optimized with SWO; F-IMRT was based on S-IMRT and the segments were edited for lowering the dose received by normal tissues. The paired plans were analyzed by comparing the total number of segments, monitor units, the homogeneity index and conformity index of the target volumes and the dose delivered to organs at risk (OAR) including spinal cord, brain stem, optic nerves, chiasm, parotids and larynx. The study exhibited that the total number of segments and monitor units of S-IMRT and F-IMRT were around 25.3%, 3.4% less than those of C-IMRT respectively. The HI and CI indexes of target volumes among three kinds of plans did not show the significant difference. The doses received by spinal cord, brain stem, parotids, larynx were decreased at S-IMRT and F-IMRT as compared to C-IMRT; the highest doses delivered to chiasm and optic nerves were S-IMRT, the next C-IMRT, the lowest F-IMRT. This study showed that the SWO function could substantially reduce the total number of segments of step-and-shoot IMRT plans and the SE function had the incredible ability to lower the dose received by normal tissues.

Intensity modulated radiation therapy (IMRT) is increasingly employed in glioblastoma (GBM) treatment. The present work aimed to assess which clinical-dosimetric scenario could benefit the most from IMRT application, with respect to three-dimensional conformal radiation therapy (3D-CRT). The number of organs at risk (OARs) overlapping the planning target volume (PTV) was the parameter describing the clinical-dosimetric pattern. Based on the results, a dosimetric decision criterion to select the most appropriate treatment technique is provided. Seventeen previously irradiated patients were retrieved and re-planned with both 3D-CRT and IMRT. The prescribed dose was 60 Gy/30fx. The cases were divided into 4 groups (4 patients in each group). Each group represents the scenario where 0, 1, 2 or 3 OARs overlapped the target volume, respectively. Furthermore, in one case, 4 OARs overlapped the PTV. The techniques were compared also in terms of irradiated healthy brain tissue. The results were evaluated by paired t-test. IMRT always provided better target coverage (V95%) than 3D-CRT, regardless the clinical-dosimetric scenario: difference ranged from 0.82% (p = 0.4) for scenario 0 to 7.8% (p = 0.02) for scenario 3, passing through 2.54% (p = 0.18) and 5.93% (p = 0.08) for scenario 1 and 2, respectively. IMRT and 3D-CRT achieved comparable results in terms of dose homogeneity and conformity. Concerning the irradiation of serial-kind OARs, both techniques provided nearly identical results. A statistically significant dose reduction to the healthy brain in favor of IMRT was scored. IMRT seems a superior technique compared to 3D-CRT when there are multiple overlaps between OAR and PTV. In this scenario, IMRT allows for a better target coverage while maintaining equivalent OARs sparing and reducing healthy brain irradiation. The results from our patients dataset suggests that the overlap of three OARs can be used as a dosimetric criterion to select which patients should receive IMRT treatment.

This planning study was performed to compare stereotactic linac based radiosurgery of Arteriovenous Malformations (AVM) with current Helical Tomotherapy (HT) and future HT techniques. For 10 patients with AVM, dose distributions and treatment times of “regular” HT delivery (Reg 2.5/1/0.6 cm field width), Running-Start-Stop Treatment (RSS 5/2.5 cm), Axial Mode (Axial 5 cm) and Dynamic Jaw/Dynamic Couch delivery with a maximum field width of 5 cm (DJDC 5) were analysed and compared to linac-based stereotactic radiosurgery. Axial produced the fastest treatment (Axial 4:47 min vs. Linac 32:42 min) at the cost of large brain exposure (V_10% 289 ml). Except for Reg 0.6, all other HT techniques achieved significantly shorter treatment times than linac-based treatment (e.g. Reg 1, 19:42 min, DJDC 6:30 min). However, high-dose brain exposure (V_60%) was higher in all HT plans (e.g. Reg 0.6, 10 ml, Linac 9 ml), and only Reg 0.6 showed better low-dose exposure (V_10% of 167 ml vs. 199 ml, not significant). Neither current nor future HT modes in their current version outperformed linac-based stereotactic radiosurgery. However, AVM with special geometry might still benefit from HT.

The exquisite soft-tissue contrast of magnetic resonance imaging (MRI) has meant that the technique is having an increasing role in contouring the gross tumor volume (GTV) and organs at risk (OAR) in radiation therapy treatment planning systems (TPS). MRI-planning scans from diagnostic MRI scanners are currently incorporated into the planning process by being registered to CT data. The soft-tissue data from the MRI provides target outline guidance and the CT provides a solid geometric and electron density map for accurate dose calculation on the TPS computer. There is increasing interest in MRI machine placement in radiotherapy clinics as an adjunct to CT simulators. Most vendors now offer 70 cm bores with flat couch inserts and specialised RF coil designs. We would refer to these devices as MR-simulators. There is also research into the future application of MR-simulators independent of CT and as in-room image-guidance devices. It is within the background of this increased interest in the utility of MRI in radiotherapy treatment planning that this paper is couched. The paper outlines publications that deal with standard MRI sequences used in current clinical practice. It then discusses the potential for using processed functional diffusion maps (fDM) derived from diffusion weighted image sequences in tracking tumor activity and tumor recurrence. Next, this paper reviews publications that describe the use of MRI in patient-management applications that may, in turn, be relevant to radiotherapy treatment planning. The review briefly discusses the concepts behind functional techniques such as dynamic contrast enhanced (DCE), diffusion-weighted (DW) MRI sequences and magnetic resonance spectroscopic imaging (MRSI). Significant applications of MR are discussed in terms of the following treatment sites: brain, head and neck, breast, lung, prostate and cervix. While not yet routine, the use of apparent diffusion coefficient (ADC) map analysis indicates an exciting future application for functional MRI. Although DW-MRI has not yet been routinely used in boost adaptive techniques, it is being assessed in cohort studies for sub-volume boosting in prostate tumors.

The purpose of this study is to evaluate the real-time respiratory motion of the prostate and surrounding tissues/organs in the supine and prone positions and to investigate, using cine-MRI, whether a belly board can reduce respiratory-induced motion in the prone position. Cine-MRI scans were made of 13 volunteers in the supine and prone positions on a flat board and in two different prone positions using a belly board. Images in cine mode were recorded for 20 seconds. For each session, the points of interest (POIs) were located at the apex, base, mid-anterior surface and mid-posterior surface of the prostate; the tip of the seminal vesicle; the pubic symphysis; and the sacrum. The maximum range and standard deviation (SD) of the displacement from the mean value were calculated. The SDs for each of the four different positions were compared using a paired t-test. Respiratory-induced prostate motion was significantly larger in the prone position than in the supine position. However, when a belly board was used in the prone position, motion in the prostate and surrounding tissues/organs was significantly reduced. There were no significant differences between the two different positions using a belly board in any of the POIs.

The fluorescence of paired human breast malignant and normal tissue samples was investigated using a novel fluorescence spectroscopic (S³-LED) ratiometer unit with no moving parts. This device can measure the emission spectra of key native organic biomolecules such as tryptophan, tyrosine, collagen and elastin within tissues by using LED (light emitting diode) excitation sources coupled to an optical fiber. With this device, the spectral profiles of 11 paired breast cancerous and normal samples from 11 patients with breast carcinoma were obtained. In each of the 11 cases, marked increases in the tryptophan levels were found in the breast carcinoma samples when compared to the normal breast tissues. In the breast cancer samples, there were also consistently higher ratios of the 340 to 440 nm and the 340 to 460 nm intensity peaks after 280 nm excitation, likely representing an increased tryptophan to NADH ratio in the breast cancer samples. This difference was seen in the spectral profiles of the breast cancer patients regardless of whether they were HER2 positive or negative or hormone receptor positive or negative, and was found regardless of meno-pausal status, histology, stage, or tumor grade.

Magnetic drug targeting is a drug delivery system that can be used in loco-regional cancer treatment. Coated magnetic particles, called carriers, are very useful for delivering chemotherapeutic drugs. Magnetic carriers were synthesized by co-precipitation of iron oxide followed by coating with polyvinyl pyrrolidone (PVP). Characterization was performed using X-ray diffraction, TEM, TGA, FTIR and UV-Vis Spectroscopy. Magnetite (Fe₃O₄) remained as the core of the carrier. The amount of PVP bound to the iron oxide nanoparticles was estimated by thermogravimetric analysis (TGA) and the attachment of PVP to the iron oxide nanoparticles confirmed by FTIR analysis. The loading efficiency of Epirubicin hydrochloride onto the PVP coated and uncoated iron oxide nanoparticles was measured at intervals such as 1 hr and 24 hrs by UV-Vis Spectroscopy. The binding of Epirubicin hydrochloride to the PVP coated and uncoated iron oxide nanoparticles were confirmed by FTIR analysis. The present findings showed that Epirubicin hydrochloride loaded PVP coated iron oxide nanoparticles are promising for magnetically targeted drug delivery. The drug displayed increased cell cytotoxicity at lower concentrations when conjugated with the nanoparticles than being administered conventionally as individual drugs.

Platinum-based chemotherapy is a primary treatment for patients with advanced non-small cell lung cancer (NSCLC). Considering individual differences, an effective and convenient method is urgently needed to identify the sensitivity of individual patient to platinum based regimen. Genetic variants in DNA repair genes are presumed to represent important determinants of drug efficacy. Our previous studies have demonstrated the involvement of xeroderma pigmentosum group A (XPA) codon23 and xeroderma pigmentosum group D (XPD) codon751 single-nucleotide polymorphisms (SNPs) in clinical response to platinum based chemotherapy in advanced NSCLC patients. Thus, a follow-up study was carried out to investigate the relevance of these genotypes and survival of the cohort (n = 115). The three-dimensional (3-D), polyacrylamide gel-based DNA microarray method was used to assess the genotypes of XPA and XPD in peripheral lymphocytes. Log-rank test revealed that the variant genotypes of XPA23 (A/G+G/G) were associated with significantly longer progression-free survival (PFS) (6.0 m vs. 10.6 m, log-rank P = 0.001) and overall survival (OS) (11.2 m vs. 20.8 m, log-rank P = 0.001). In Cox proportional hazards model, the hazard ratio (HR) for death in patients with G allele was 0.65 (P = 0.049). While no significant differences were observed in PFS or OS according to XPD Lys751Gln genotypes (log-rank P > 0.05). In combination with our previous short-term clinical results, this study further confirmed that by detecting the SNPs in blood cells, XPA A23G polymorphic variants might be a promising biomarker in predicting a favor prognosis of NSCLC patients and be helpful towards designing individualized treatments.