Evaluation of the MVCT-based radiomic features as prognostic factor in patients with head and neck squamous cell carcinoma.

BACKGROUND: Megavoltage computed tomography (MVCT) images acquired during each radiotherapy session may be useful for delta radiomics. However, no studies have examined whether the MVCT-based radiomics has prognostic power. Therefore, the purpose of this study was to examine the prognostic power of the MVCT-based radiomics for head and neck squamous cell carcinoma (HNSCC) patients. METHODS: 100 HNSCC patients who received definitive radiotherapy were analyzed and divided into two groups: training (n = 70) and test (n = 30) sets. MVCT images obtained using TomoTherapy for the first fraction of radiotherapy and planning kilovoltage CT (kVCT) images obtained using Aquilion LB CT scanner were analyzed. Primary gross tumor volume (GTV) was propagated from kVCT to MVCT images using rigid registration, and 107 radiomic features were extracted from the GTV in MVCT and kVCT images. Least absolute shrinkage and selection operator (LASSO) Cox regression model was used to examine the association between overall survival (OS) and rad score calculated for each patient by weighting the feature value through the coefficient when features were selected. Then, the predictive values of MVCT-based and kVCT-based rad score and patient-, treatment-, and tumor-specific factors were evaluated. RESULTS: C-indices of the rad score for MVCT- and kVCT-based radiomics were 0.667 and 0.685, respectively. The C-indices of 6 clinical factors were 0.538-0.622. The 3-year OS was significantly different between high- and low-risk groups according to the MVCT-based rad score (50% vs. 83%; p < 0.01). CONCLUSIONS: Our results suggested that MVCT-based radiomics had stronger prognostic power than any single clinical factor and was a useful prognostic factor when predicting OS in HNSCC patients.

Phase I trial of myeloablative conditioning with 3-day total marrow and lymphoid irradiation for leukemia.

This prospective phase I trial aimed to determine the recommended dose of 3-day total marrow and lymphoid irradiation (TMLI) for a myeloablative conditioning regimen by increasing the dose per fraction. The primary end-point of this single-institution dose escalation study was the recommended TMLI dose based on the frequency of dose-limiting toxicity (DLT) ≤100 days posthematopoietic stem cell transplantation (HSCT); a 3 + 3 design was used to evaluate the safety of TMLI. Three dose levels of TMLI (14/16/18 Gy in six fractions over 3 days) were set. The treatment protocol began at 14 Gy. Dose-limiting toxicities were defined as grade 3 or 4 nonhematological toxicities. Nine patients, with a median age of 42 years (range, 35-48), eight with acute lymphoblastic leukemia and one with chronic myeloblastic leukemia, received TMLI followed by unrelated bone marrow transplant. The median follow-up period after HSCT was 575 days (range, 253-1037). Three patients were enrolled for each dose level. No patient showed DLT within 100 days of HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. All patients achieved neutrophil engraftment at a median of 19 days (range, 14-25). One-year overall and disease-free survival rates were 83.3% and 57.1%, respectively. Three patients experienced relapse, and no nonrelapse mortality was documented during the observation period. One patient died due to disease relapse 306 days post-HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. The efficacy evaluation of this regimen is currently being planned in a phase II study.

Functional Impairment and Periodontitis in Rheumatoid Arthritis.

BACKGROUND: This study explored the association of functional impairment due to rheumatoid arthritis (RA) and RA disease activity with periodontal disease in patients with RA. METHODS: Ninety-three patients with RA were included. Their RA functional status was assessed using the Steinbrocker classification. The serum level of matrix metalloproteinase-3 (MMP-3) was used as an indicator of RA disease activity. Probing depth (PD) and clinical attachment level (CAL) were used as indicators of periodontal status. We examined the association of RA severity and MMP-3 levels with periodontal status using a generalised linear model (GLM). RESULTS: In a multivariate GLM, the coefficient for the mean PD was significantly positive in those with RA severity classes III or IV (reference: class I; ß = 0.14; 95% confidence interval [CI], 0.03-0.25; P = .02) independent of other confounding variables. In multivariate GLM using the mean CAL as the dependent variable, the coefficient was significant in patients with high MMP-3 levels (10 ng/mL; ß = 0.005; 95% CI, 0.001-0.008; P = .02). CONCLUSIONS: Functional impairment due to RA may affect PD, and high serum levels of MMP-3 may affect CAL.

Relationship between Tooth Loss and the Medications Used for the Treatment of Rheumatoid Arthritis in Japanese Patients with Rheumatoid Arthritis: A Cross-Sectional Study.

BACKGROUND: There is limited information regarding the association between tooth loss and the medications used for the treatment of rheumatoid arthritis (RA). Here, we examined the association between tooth loss, disease severity, and drug treatment regimens in RA patients. METHOD: This study recruited 94 Japanese patients with RA. The severity of RA was assessed using the Steinbrocker classification of class and stage. Data on RA medications were obtained from medical records. We examined the associations between tooth loss, RA severity, and drug treatment regi mens using multinomial logistic regression analyses. RESULTS: Patients with 1-19 teeth had significantly higher odds ratios (ORs) of taking methotrexate (MTX) (OR, 8.74; 95% confidence interval (CI), 1.11-68.8) and biologic disease-modifying antirheumatic drugs (bDMARDs) (OR, 21.0; 95% CI, 1.3-339.1) compared to those with 27-28 teeth when adjusted for RA severity (class). Furthermore, patients with 1-19 teeth had significantly higher ORs of taking MTX (OR, 9.71; 95% CI, 1.22-77.1) and bDMARDs (OR, 50.2; 95% CI, 2.55-990.6) compared to those with 27-28 teeth when adjusted for RA severity (stage). CONCLUSION: RA patients with fewer teeth were more likely to take stronger RA therapies, independent of RA severity and other factors.

Association Between the Extent of Periodontal Inflammation and the Severity of Rheumatoid Arthritis in Japanese Patients With Rheumatoid Arthritis.

OBJECTIVE: Periodontal inflammation can affect the progression of rheumatoid arthritis (RA), and RA drugs may influence the periodontal condition of patients with RA. We examined whether the association between periodontal inflammation and the severity of RA is influenced by RA medication. METHODS: This cross-sectional study recruited 98 Japanese patients with RA from an orthopaedic clinic. We assessed the severity of RA using the Steinbrocker class and stage. The periodontal inflamed surface area (PISA) was used as an indicator of periodontal status. We obtained data on RA medications from medical records. We examined the associations among periodontal tissue inflammation, RA medications, and RA severity using multinomial logistic regression analyses. RESULTS: In univariate multinomial logistic regression analyses, no significant association between PISA score and RA severity was observed. There was no significant association between PISA score and RA severity in multivariate analyses not including variables about RA drugs as independent variables. However, in multivariate analyses adjusted for RA drugs and other confounding variables, patients with a PISA >550 mm2 had significantly higher odds ratios (ORs) for Steinbrocker class III-IV and stage III-IV (OR, 20.24; 95% confidence interval [CI], 1.78-229.85 and OR, 12.42; 95% CI, 1.79-86.49, respectively) compared to patients with PISA score ≤550 mm2. CONCLUSION: The extent of periodontal inflammation is associated with the severity of RA independent of RA medications.

Evaluation of the effect of user-guided deformable image registration of thoracic images on registration accuracy among users.

User-guided deformable image registration (DIR) has allowed users to actively participate in the DIR process and is expected to improve DIR accuracy. The purpose of this study was to evaluate the time required for and effect of user-guided DIR on registration accuracy for thoracic images among users. In this study, 4-dimensional computed tomographic images of 10 thoracic cancer patients were used. The dataset for these patients was provided by DIR-Lab (www.dir-lab.com) and included a coordinate list of anatomical landmarks (300 bronchial bifurcations). Four medical physicists from different institutions performed DIR between peak-inhale and peak-exhale images with/without the user-guided DIR tool, Reg Refine, implemented in MIM Maestro (MIM software, Cleveland, OH). DIR accuracy was quantified by using target registration errors (TREs) for 300 anatomical landmarks in each patient. The average TREs with user-guided DIR in the 10 images by the 4 medical physicists were 1.48, 1.80, 3.46, and 3.55 mm, respectively, whereas the TREs without user-guided DIR were 3.28, 3.45, 3.56, and 3.28 mm, respectively. The average times taken by the 4 physicists to use the user-guided DIR were 10.0, 6.7, 7.1, and 8.0 min, respectively. This study demonstrated that user-guided DIR can improve DIR accuracy and requires only a moderate amount of time (<10 min). However, 2 of the 4 users did not show much improvement in DIR accuracy, which indicated the necessity of training prior to use of user-guided DIR.

Evaluation of multi-institutional end-to-end testing for post-operative spine stereotactic body radiation therapy.

BACKGROUND AND PURPOSE: Post-operative spine stereotactic body radiation therapy (SBRT) represents a significant challenge as there are many restrictions on beam geometry to avoid metal hardware as it surrounds the target volume. In this study, an international multi-institutional end-to-end test using an in-house spine phantom was developed and executed. The aim was to evaluate the impact of titanium spine hardware on planned and delivered dose for post-operative spine SBRT. MATERIALS AND METHODS: Five centers performed simulation, planning and irradiation of the spine phantom, with/without titanium metal hardware (MB/B), following our pre-specified protocol. The doses were calculated using the centers' treatment planning system (TPS) and measured with radiophotoluminescent glass dosimeters (RPLDs) embedded within each phantom. RESULTS: The dose differences between the RPLD measured and calculated doses in the target region were within ±â€¯5% for both phantoms studied. Differences greater than 5% were observed for the spinal cord and the out-of-the target regions due to steeper dose gradient regions that are created in these plans. Dose measurements within ±â€¯3% were observed between RPLDs that were embedded in MB and B inserts. For the spinal cord and the out-of-target regions surrounded by metal hardware, the dose measured using RPLDs was within 3% different near the titanium screws compared to the dose measured near only the metal rods. CONCLUSION: We have successfully performed the first multi-institutional end-to-end dose analysis using an in-house phantom built specifically for post-operative spine SBRT. The differences observed between the measured and planned doses in the presence of metal hardware were clinically insignificant.

Energy dependence of a radiophotoluminescent glass dosimeter for HDR 192 Ir brachytherapy source.

PURPOSE: We determined correction factors for absorbed dose energy dependence and intrinsic energy dependence for measurements of absorbed dose to water around an 192 Ir source using a radiophotoluminescent glass dosimeter (RPLD) calibrated with a 4-MV photon beam. METHODS: The ratio of the absorbed dose to the water and the average absorbed dose to RPLD for the 192 Ir beam relative to the same ratio in a 4 MV photon beam defines the absorbed dose energy dependence and was determined at distances of 2-10 cm (at intervals of 1 cm) from the 192 Ir source in a water phantom using the egs_chamber user code. The RPLD was calibrated to measure absorbed dose to water, Dw , in a 4 MV photon beam using an ionization chamber, which was also used to measure absorbed dose to water, Dw , in a water phantom using the 192 Ir source. The detector response radiophotoluminescence (RPL signal per average absorbed dose in the detector) in the 192 Ir beam relative to that in the 4 MV photon beam (the relative intrinsic efficiency) was determined experimentally. Finally, the beam quality correction factor was obtained as the quotient between the absorbed dose energy dependence and the relative intrinsic efficiency and corrects for the difference between the beam quality Q0 used at calibration and the beam quality Q used in the measurements. RESULTS: The relative dose ratio of the average absorbed dose to water relative to RPLD ranged from 0.930 to 0.746, and the beam quality correction factor ranged from 0.999 to 0.794 for distances of 2-10 cm from the 192 Ir source. The relative detector response to an 192 Ir source and a 4-MV photon beam was 0.930, and it did not vary significantly with distance. CONCLUSIONS: These results demonstrate that corrections for absorbed dose energy dependence and intrinsic energy dependence are required when using an RPLD to measure with sources different from the reference source providing the primary calibration.

Influence of plaque control on the relationship between rheumatoid arthritis and periodontal health status among Japanese rheumatoid arthritis patients.

BACKGROUND: Functional disability of the finger joints in rheumatoid arthritis (RA) patients could affect their oral hygiene and periodontal status because of poor plaque control. We examined the influence of plaque control on the relationship between the severity of RA and periodontal status in RA patients. METHODS: This study recruited 89 Japanese RA patients who reported no difficulty in performing oral hygiene. We assessed RA severity using four indices: the Steinbrocker stage and class, the Health Assessment Questionnaire (HAQ) and the Disease Activity Score (DAS). Probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) were taken as parameters of periodontal status. Oral hygiene status was assessed using the plaque index (PlI). We examined the association between the severity of RA and periodontal parameters using multivariable linear regression analyses. RESULTS: In multivariable linear regression analyses not including PlI, Steinbrocker stage III-IV patients had significantly higher PlI scores and greater PD compared with those of stage I. The class III-IV patients had significantly higher PlI scores and greater PD. Patients with an HAQ score ≥0.5 had a significantly higher PlI score than those with an HAQ score of 0. However, when PlI was added to each multivariable model as an independent variable, no significant relationship between RA severity and periodontal status was observed. CONCLUSIONS: This study suggests that it is important to consider the influence of plaque control when assessing the relationship between RA severity and periodontal health status in RA patients.

Impact of a commercially available model-based dose calculation algorithm on treatment planning of high-dose-rate brachytherapy in patients with cervical cancer.

We evaluated the impact of model-based dose calculation algorithms (MBDCAs) on high-dose-rate brachytherapy (HDR-BT) treatment planning for patients with cervical cancer. Seven patients with cervical cancer treated using HDR-BT were studied. Tandem and ovoid applicators were used in four patients, a vaginal cylinder in one, and interstitial needles in the remaining two patients. MBDCAs were applied to the Advanced Collapsed cone Engine (ACE; Elekta, Stockholm, Sweden). All plans, which were originally calculated using TG-43, were re-calculated using both ACE and Monte Carlo (MC) simulations. Air was used as the rectal material. The mean difference in the rectum D2cm3 between ACErec-air and MCrec-air was 8.60 ± 4.64%, whereas that in the bladder D2cm3 was -2.80 ± 1.21%. Conversely, in the small group analysis (n = 4) using water instead of air as the rectal material, the mean difference in the rectum D2cm3 between TG-43 and ACErec-air was 11.87 ± 2.65%, whereas that between TG-43 and ACErec-water was 0.81 ± 2.04%, indicating that the use of water as the rectal material reduced the difference in D2cm3 between TG-43 and ACE. Our results suggested that the differences in the dose-volume histogram (DVH) parameters of TG-43 and ACE were large for the rectum when considerable air (gas) volume was present in it, and that this difference was reduced when the air (gas) volume was reduced. Also, ACE exhibited better dose calculation accuracy than that of TG-43 in this situation. Thus, ACE may be able to calculate the dose more accurately than TG-43 for HDR-BT in treating cervical cancers, particularly for patients with considerable air (gas) volume in the rectum.

Field-size correction factors of a radiophotoluminescent glass dosimeter for small-field and intensity-modulated radiation therapy beams.

PURPOSE: We evaluated the energy responses of a radiophotoluminescent glass dosimeter (RPLD) to variations in small-field and intensity-modulated radiation therapy (IMRT) conditions using experimental measurements and Monte Carlo simulation. METHODS: Several sizes of the jaw and multileaf collimator fields and various plan-class IMRT-beam measurements were performed using the RPLD and an ionization chamber. The field-size correction factor for the RPLD was determined for 6- and 10-MV x rays. This correction factor, together with the perturbation factor, was also calculated using Monte Carlo simulation with the EGSnrc/egs_chamber user code. In addition, to evaluate the response of the RPLD to clinical-class-specific reference fields, the field-size correction factor for the clinical IMRT plan was measured. RESULTS: The calculated field-size correction factor ranged from 1.007 to 0.981 (for 6-MV x rays) and from 1.012 to 0.990 (for 10-MV x rays) as the jaw-field size ranged from 1 × 1 cm2 to 20 × 20 cm2 . The atomic composition perturbation factor for these jaw fields decreased by 3.2% and 1.9% for the 6- and 10-MV fields, respectively. The density perturbation factor was unity for field sizes ranging from 3 × 3 cm2 to 20 × 20 cm2 , whereas that for field sizes ranging from 3 × 3 cm2 to 1 × 1 cm2 decreased by 3.2% (for 6-MV x rays) and 4.3% (for 10-MV x rays). The volume-averaging factor rapidly increased for field sizes below 1.6 × 1.6 cm2 . The results for the MLC fields were similar to those for the jaw fields. For plan-class IMRT beams, the field-size correction and perturbation factors were almost unity. The difference between the doses measured using the RPLD and ionization chamber was within 1.2% for the clinical IMRT plan at the planning-target volume (PTV) region. CONCLUSIONS: For small fields of size 1.6 × 1.6 cm2 or less, it was clarified that the volume averaging and density perturbation were the dominant effects responsible for the variation in the RPLD response. Moreover, perturbation correction is required when measuring a field size 1.0 × 1.0 cm2 or less. Under the IMRT conditions, the difference in the responses of the RPLD between the reference conditions and the PTV region calculated by Monte Carlo simulation did not exceed 0.8%. These results indicate that it is feasible to measure IMRT dosage using an RPLD at the PTV region.

Changes in deviation of absorbed dose to water among users by chamber calibration shift.

PURPOSE: The JSMP01 dosimetry protocol had adopted the provisional 60Co calibration coefficient [Formula: see text], namely, the product of exposure calibration coefficient N C and conversion coefficient k D,X. After that, the absorbed dose to water D w standard was established, and the JSMP12 protocol adopted the [Formula: see text] calibration. In this study, the influence of the calibration shift on the measurement of D w among users was analyzed. MATERIALS AND METHODS: The intercomparison of the D w using an ionization chamber was annually performed by visiting related hospitals. Intercomparison results before and after the calibration shift were analyzed, the deviation of D w among users was re-evaluated, and the cause of deviation was estimated. RESULTS: As a result, the stability of LINAC, calibration of the thermometer and barometer, and collection method of ion recombination were confirmed. The statistical significance of standard deviation of D w was not observed, but that of difference of D w among users was observed between N C and [Formula: see text] calibration. CONCLUSION: Uncertainty due to chamber-to-chamber variation was reduced by the calibration shift, consequently reducing the uncertainty among users regarding D w. The result also pointed out uncertainty might be reduced by accurate and detailed instructions on the setup of an ionization chamber.

Quantitative analysis of in-air output ratio.

Output factor (Scp) is one of the important factors required to calculate monitor unit (MU), and is divided into two components: phantom scatter factor (Sp) and in-air output ratio (Sc). Generally, Sc for arbitrary fields are calculated using several methods based on Sc determined by the absorbed dose measurement for several square fields. However, there are calculation errors when the treatment field has a large aspect ratio and the opening of upper and lower collimator are exchanged. To determine Sc accurately, scattered photons from the treatment head and backscattered particles into the monitor chamber must be analyzed individually. In this report, a simulation model that agreed well with measured Sc was constructed and dose variation by scattered photons from the treatment head and by backscattered particles into the monitor chamber was analyzed quantitatively. The results showed that the contribution of scattered photons from the primary collimator was larger than that of the flattening filter, and backscattered particles were affected by not only the upper jaw but also the lower jaw. In future work, a new Sc determination algorism based on the result of this report will be proposed.

Evaluation of beam hardening and photon scatter by brass compensator for IMRT.

When a brass compensator is set in a treatment beam, beam hardening may take place. This variation of the energy spectrum may affect the accuracy of dose calculation by a treatment planning system and the results of dose measurement of brass compensator intensity modulated radiation therapy (IMRT). In addition, when X-rays pass the compensator, scattered photons are generated within the compensator. Scattered photons may affect the monitor unit (MU) calculation. In this study, to evaluate the variation of dose distribution by the compensator, dose distribution was measured and energy spectrum was simulated using the Monte Carlo method. To investigate the influence of beam hardening for dose measurement using an ionization chamber, the beam quality correction factor was determined. Moreover, to clarify the effect of scattered photons generated within the compensator for the MU calculation, the head scatter factor was measured and energy spectrum analyses were performed. As a result, when X-rays passed the brass compensator, beam hardening occurred and dose distribution was varied. The variation of dose distribution and energy spectrum was larger with decreasing field size. This means that energy spectrum should be reproduced correctly to obtain high accuracy of dose calculation for the compensator IMRT. On the other hand, the influence of beam hardening on k(Q) was insignificant. Furthermore, scattered photons were generated within the compensator, and scattered photons affect the head scatter factor. These results show that scattered photons must be taken into account for MU calculation for brass compensator IMRT.