High-dose intensity-modulated chemoradiotherapy in vulvar squamous cell carcinoma: Outcome and toxicity.

INTRODUCTION: To evaluate clinical outcomes, pattern of failure, and toxicity after high-dose intensity-modulated radiation therapy (IMRT) for advanced vulvar cancer. METHODS: In this IRB approved retrospective study, the charts of women with histologically confirmed, non-metastatic vulvar cancer consecutively treated at our institution from 2012 to 2018 were reviewed to identify patients that received high-dose IMRT with curative intent. The treatment compliance, toxicities, and patterns of failure were investigated. Actuarial local, regional and distant recurrence and survival were estimated using Kaplan-Meier method and compared using log rank test. RESULTS: Twenty-six patients were identified, 23 were unresectable, and 3 refused surgery. Fifteen patients (58%) had inguinal node metastases; 10(38%) had pelvic node metastases. Elective surgical staging of groins was performed in 9-patients. Median tumor dose was 65.4Gy. Concurrent platinum-based chemotherapy was administered in 22(84.6%) patients. Complete response (CR) was achieved in 21/26 (80.7%) patients. Five patients had persistent disease following treatment and one sustained recurrence 5-months following radiotherapy. All persistent or recurrent disease occurred inside the irradiated volume. Median follow-up was 19 months (3-52 months). Actuarial 1-year local, regional and distant controls were 72.4%, 85.4%, and 86%, respectively. One and 2-year overall survivals were 91% and 62%, respectively. Complete response at 3-months was a strong predictor for overall survival (1-yr OS 73% vs 27%, HR 7.1 (95% CI 1.2-44); p = 0.01). Lymph node metastases adversely affected overall survival (2-yr OS 49% vs. 83%, p = 0.09). Grade 3-4 late urinary and soft-tissue toxicity was seen in 5 patients. Tumor doses >66 Gy (p = 0.03) and prior pelvic radiotherapy (p = 0.002) predicted grade 3-4 toxicity. CONCLUSION: High-dose IMRT for vulvar cancer achieves high rates of local control with acceptable dose dependent long-term toxicity.

Accounting for reconstruction kernel-induced variability in CT radiomic features using noise power spectra.

Large variability in computed tomography (CT) radiomics feature values due to CT imaging parameters can have subsequent implications on the prognostic or predictive significance of these features. Here, we investigated the impact of pitch, dose, and reconstruction kernel on CT radiomic features. Moreover, we introduced correction factors to reduce feature variability introduced by reconstruction kernels. The credence cartridge radiomics and American College of Radiology (ACR) phantoms were scanned on five different scanners. ACR phantom was used for 3-D noise power spectrum (NPS) measurements to quantify correlated noise. The coefficient of variation (COV) was used as the variability assessment metric. The variability in texture features due to different kernels was reduced by applying the NPS peak frequency and region of interest (ROI) maximum intensity as correction factors. Most texture features were dose independent but were strongly kernel dependent, which is demonstrated by a significant shift in NPS peak frequency among kernels. Percentage improvement in robustness was calculated for each feature from original and corrected %COV values. Percentage improvements in robustness of 19 features were in the range of 30% to 78% after corrections. We show that NPS peak frequency and ROI maximum intensity can be used as correction factors to reduce variability in CT texture feature values due to reconstruction kernels.

Intrinsic dependencies of CT radiomic features on voxel size and number of gray levels.

PURPOSE: Many radiomics features were originally developed for non-medical imaging applications and therefore original assumptions may need to be reexamined. In this study, we investigated the impact of slice thickness and pixel spacing (or pixel size) on radiomics features extracted from Computed Tomography (CT) phantom images acquired with different scanners as well as different acquisition and reconstruction parameters. The dependence of CT texture features on gray-level discretization was also evaluated. METHODS AND MATERIALS: A texture phantom composed of 10 different cartridges of different materials was scanned on eight different CT scanners from three different manufacturers. The images were reconstructed for various slice thicknesses. For each slice thickness, the reconstruction Field Of View (FOV) was varied to render pixel sizes ranging from 0.39 to 0.98 mm. A fixed spherical region of interest (ROI) was contoured on the images of the shredded rubber cartridge and the 3D printed, 20% fill, acrylonitrile butadiene styrene plastic cartridge (ABS20) for all phantom imaging sets. Radiomic features were extracted from the ROIs using an in-house program. Features categories were: shape (10), intensity (16), GLCM (24), GLZSM (11), GLRLM (11), and NGTDM (5), fractal dimensions (8) and first-order wavelets (128), for a total of 213 features. Voxel-size resampling was performed to investigate the usefulness of extracting features using a suitably chosen voxel size. Acquired phantom image sets were resampled to a voxel size of 1 × 1 × 2 mm3 using linear interpolation. Image features were therefore extracted from resampled and original datasets and the absolute value of the percent coefficient of variation (%COV) for each feature was calculated. Based on the %COV values, features were classified in 3 groups: (1) features with large variations before and after resampling (%COV >50); (2) features with diminished variation (%COV <30) after resampling; and (3) features that had originally moderate variation (%COV <50%) and were negligibly affected by resampling. Group 2 features were further studied by modifying feature definitions to include voxel size. Original and voxel-size normalized features were used for interscanner comparisons. A subsequent analysis investigated feature dependency on gray-level discretization by extracting 51 texture features from ROIs from each of the 10 different phantom cartridges using 16, 32, 64, 128, and 256 gray levels. RESULTS: Out of the 213 features extracted, 150 were reproducible across voxel sizes, 42 improved significantly (%COV <30, Group 2) after resampling, and 21 had large variations before and after resampling (Group 1). Ten features improved significantly after definition modification effectively removed their voxel-size dependency. Interscanner comparison indicated that feature variability among scanners nearly vanished for 8 of these 10 features. Furthermore, 17 out of 51 texture features were found to be dependent on the number of gray levels. These features were redefined to include the number of gray levels which greatly reduced this dependency. CONCLUSION: Voxel-size resampling is an appropriate pre-processing step for image datasets acquired with variable voxel sizes to obtain more reproducible CT features. We found that some of the radiomics features were voxel size and gray-level discretization-dependent. The introduction of normalizing factors in their definitions greatly reduced or removed these dependencies.

Health-related quality-of-life changes due to high-dose-rate brachytherapy, low-dose-rate brachytherapy, or intensity-modulated radiation therapy for prostate cancer.

PURPOSE: To compare urinary, bowel, and sexual health-related quality-of-life (HRQOL) changes due to high-dose-rate (HDR) brachytherapy, low-dose-rate (LDR) brachytherapy, or intensity-modulated radiation therapy (IMRT) monotherapy for prostate cancer. METHODS AND MATERIALS: Between January 2002 and September 2013, 413 low-risk or favorable intermediate-risk prostate cancer patients were treated with HDR brachytherapy monotherapy to 2700-2800 cGy in two fractions (n = 85), iodine-125 LDR brachytherapy monotherapy to 14,500 cGy in one fraction (n = 249), or IMRT monotherapy to 7400-8100 cGy in 37-45 fractions (n = 79) without pelvic lymph node irradiation. No androgen deprivation therapy was given. Patients used an international prostate symptoms score questionnaire, an expanded prostate cancer index composite-26 bowel questionnaire, and a sexual health inventory for men questionnaire to assess their urinary, bowel, and sexual HRQOL, respectively, pretreatment and at 1, 3, 6, 9, 12, and 18 months posttreatment. RESULTS: Median follow-up was 32 months. HDR brachytherapy and IMRT patients had significantly less deterioration in their urinary HRQOL than LDR brachytherapy patients at 1 and 3 months after irradiation. The only significant decrease in bowel HRQOL between the groups was seen 18 months after treatment, at which point IMRT patients had a slight, but significant, deterioration in their bowel HRQOL compared with HDR and LDR brachytherapy patients. HDR brachytherapy patients had worse sexual HRQOL than both LDR brachytherapy and IMRT patients after treatment. CONCLUSIONS: IMRT and HDR brachytherapy cause less severe acute worsening of urinary HRQOL than LDR brachytherapy. However, IMRT causes a slight, but significant, worsening of bowel HRQOL compared with HDR and LDR brachytherapy.

Lipiodol as a fiducial marker for image-guided radiation therapy for bladder cancer.

PURPOSE: To evaluate Lipiodol as a liquid, radio-opaque fiducial marker for image-guided radiation therapy (IGRT) for bladder cancer. MATERIALS AND METHODS: Between 2011 and 2012, 5 clinical T2a-T3b N0 M0 stage II-III bladder cancer patients were treated with maximal transurethral resection of a bladder tumor (TURBT) and image-guided radiation therapy (IGRT) to 64.8 Gy in 36 fractions ± concurrent weekly cisplatin-based or gemcitabine chemotherapy. Ten to 15mL Lipiodol, using 0.5mL per injection, was injected into bladder submucosa circumferentially around the entire periphery of the tumor bed immediately following maximal TURBT. The authors looked at inter-observer variability regarding the size and location of the tumor bed (CTVboost) on computed tomography scans with versus without Lipiodol. RESULTS: Median follow-up was 18 months. Lipiodol was visible on every orthogonal two-dimensional kV portal image throughout the entire, 7-week course of IGRT. There was a trend towards improved inter-observer agreement on the CTVboost with Lipiodol (p = 0.06). In 2 of 5 patients, the tumor bed based upon Lipiodol extended outside a planning target volume that would have been treated with a radiation boost based upon a cystoscopy report and an enhanced computed tomography (CT) scan for staging. There was no toxicity attributable to Lipiodol. CONCLUSIONS: Lipiodol constitutes a safe and effective fiducial marker that an urologist can use to demarcate a tumor bed immediately following maximal TURBT. Lipiodol decreases inter-observer variability in the definition of the extent and location of a tumor bed on a treatment planning CT scan for a radiation boost.

A dosimetric study of polyethylene glycol hydrogel in 200 prostate cancer patients treated with high-dose rate brachytherapy±intensity modulated radiation therapy.

BACKGROUND AND PURPOSE: We sought to analyze the effect of polyethylene glycol (PEG) hydrogel on rectal doses in prostate cancer patients undergoing radiotherapy. MATERIALS AND METHODS: Between July 2009 and April 2013, we treated 200 clinically localized prostate cancer patients with high-dose rate (HDR) brachytherapy±intensity modulated radiation therapy. Half of the patients received a transrectal ultrasound (TRUS)-guided transperineal injection of 10mL PEG hydrogel (DuraSeal™ Spinal Sealant System; Covidien, Mansfield, MA) in their anterior perirectal fat immediately prior to the first HDR brachytherapy treatment and 5mL PEG hydrogel prior to the second HDR brachytherapy treatment. Prostate, rectal, and bladder doses and prostate-rectal distances were calculated based upon treatment planning CT scans. RESULTS: There was a success rate of 100% (100/100) with PEG hydrogel implantation. PEG hydrogel significantly increased the prostate-rectal separation (mean±SD, 12±4mm with gel vs. 4±2mm without gel, p<0.001) and significantly decreased the mean rectal D2 mL (47±9% with gel vs. 60±8% without gel, p<0.001). Gel decreased rectal doses regardless of body mass index (BMI). CONCLUSIONS: PEG hydrogel temporarily displaced the rectum away from the prostate by an average of 12mm and led to a significant reduction in rectal radiation doses, regardless of BMI.

Lipiodol as a Fiducial Marker for Image-Guided Radiation Therapy for Bladder Cancer

Purpose To evaluate Lipiodol as a liquid, radio-opaque fiducial marker for image-guided radiation therapy (IGRT) for bladder cancer.Materials and Methods Between 2011 and 2012, 5 clinical T2a-T3b N0 M0 stage II-III bladder cancer patients were treated with maximal transurethral resection of a bladder tumor (TURBT) and image-guided radiation therapy (IGRT) to 64.8 Gy in 36 fractions ± concurrent weekly cisplatin-based or gemcitabine chemotherapy. Ten to 15mL Lipiodol, using 0.5mL per injection, was injected into bladder submucosa circumferentially around the entire periphery of the tumor bed immediately following maximal TURBT. The authors looked at inter-observer variability regarding the size and location of the tumor bed (CTVboost) on computed tomography scans with versus without Lipiodol.Results Median follow-up was 18 months. Lipiodol was visible on every orthogonal two-dimensional kV portal image throughout the entire, 7-week course of IGRT. There was a trend towards improved inter-observer agreement on the CTVboost with Lipiodol (p = 0.06). In 2 of 5 patients, the tumor bed based upon Lipiodol extended outside a planning target volume that would have been treated with a radiation boost based upon a cystoscopy report and an enhanced computed tomography (CT) scan for staging. There was no toxicity attributable to Lipiodol.Conclusions Lipiodol constitutes a safe and effective fiducial marker that an urologist can use to demarcate a tumor bed immediately following maximal TURBT. Lipiodol decreases inter-observer variability in the definition of the extent and location of a tumor bed on a treatment planning CT scan for a radiation boost.

High-dose-rate brachytherapy with or without intensity modulated radiation therapy as salvage treatment for an isolated, gross local recurrence of prostate cancer post-prostatectomy.

PURPOSE: To evaluate the use of high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) as salvage therapy for patients with an isolated, gross local recurrence of prostate cancer after radical prostatectomy. METHODS AND MATERIALS: Between October 2009 and May 2013, the authors treated six patients with salvage iridium-192 HDR brachytherapy ± IMRT for biopsy-proven, recurrent prostate cancer post-prostatectomy. In each patient, a pelvic MRI scan or CT scan demonstrated a nodule (range 1.6, 4.7 cm) in the prostate bed. Although prostate-specific antigen values were 0.2-9.5 ng/mL at the time of salvage brachytherapy, there was no pelvic adenopathy on CT or MRI scan, and a bone scan was negative in all cases. Five patients were treated with IMRT to 4500-5040 cGy in 25-28 fractions to the prostate bed followed by two 950 cGy HDR brachytherapy fractions separated by 1-2 weeks. A sixth patient underwent HDR brachytherapy monotherapy consisting of 3800 cGy in four fractions over 3 days. Toxicities were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Median followup was 9 months (range 3, 40 months). All six patients have been free of androgen deprivation therapy and have an undetectable prostate-specific antigen. One patient developed late Grade 2 urinary incontinence. There was no late grade ≥2 gastrointestinal toxicity. CONCLUSIONS: HDR brachytherapy ± IMRT is a safe and effective salvage therapy option for an isolated, gross local recurrence of prostate cancer after radical prostatectomy and merits further study.

X-ray imaging with amorphous selenium: X-ray to charge conversion gain and avalanche multiplication gain.

Fluoroscopy is a low dose imaging technique. As such, a very sensitive detector is required to create images of good quality. Present day flat panel active matrix read out systems introduce an amount of noise that inhibits present direct and indirect methods from producing optimal quality images at fluoroscopic exposure rates (0.1-10 microR per frame). The gain of the direct conversion approach using amorphous selenium (a-Se) was investigated to determine whether by increasing the applied electric field, a gain sufficient to overcome the noise limitations of the active matrix could be achieved. Conversion gain and avalanche multiplication in a-Se were investigated as a function of electric field from 10 to 100 V/microm. Our results show a factor of 4 increase in conversion gain is available by increasing electric field from the current standard of 10 V/microm to 100 V/microm. Furthermore, we show that avalanche multiplication can provide an additional gain of up to 25. This increase in signal is sufficient to overcome the noise level encountered in flat panel detectors and permit fully quantum noise limited operation across the whole fluoroscopic range of exposure.

Direct conversion detectors: the effect of incomplete charge collection on detective quantum efficiency.

Direct conversion detectors offer the potential for very high resolution and high quantum efficiency for x-ray imaging, however, variations in signal can arise due to incomplete charge collection. A charge transport model was developed to describe the signal and noise resulting from incomplete charge collection. This signal to noise ratio (SNR) reduction was incorporated into the cascaded systems model for a simple x-ray detector. A new excess noise factor, A(c) (termed the collection noise factor) is introduced to describe the reduction in detective quantum efficiency (DQE). The DQE is proportional to the product of the quantum efficiency and the collection noise factor. If the trapping cross sections for electrons and holes are very different, and if the detector is biased improperly, the collection noise factor can drop to as low as 50%. In addition, the signal loss due to incomplete charge collection will reduce the DQE in the presence of added noise. Because of this, the DQE generally does not continue to improve with greater detector thickness. The collection noise factor and DQE are predicted for CdZnTe, PbI2, and Se. The optimization of detector thickness should be based not only on quantum efficiency but also on the charge collection statistics, which are influenced by bias field and polarity.