Improved safety and quality in intravascular brachytherapy: A multi-institutional study using failure modes and effects analysis.

PURPOSE: Highlight safety considerations in intravascular brachytherapy (IVBT) programs, provide relevant quality assurance (QA) and safety measures, and establish their effectiveness. METHODS AND MATERIALS: Radiation oncologists, medical physicists, and cardiologists from three institutions performed a failure modes and effects analysis (FMEA) on the radiation delivery portion of IVBT. We identified 40 failure modes and rated the severity, occurrence, and detectability before and after consideration of safety practices. Risk priority numbers (RPN) and relative risk rankings were determined, and a sample QA safety checklist was developed. RESULTS: We developed a process map based on multi-institutional consensus. Highest-RPN failure modes were due to incorrect source train length, incorrect vessel diameter, and missing prior radiation history. Based on these, we proposed QA and safety measures: ten of which were not previously recommended. These measures improved occurrence and detectability: reducing the average RPN from 116 to 58 and median from 84 to 40. Importantly, the average RPN of the top 10% of failure modes reduced from 311 to 172. With QA considered, the highest risk failure modes were from contamination and incorrect source train length. CONCLUSIONS: We identified several high-risk failure modes in IVBT procedures and practical safety and QA measures to address them.

Dosimetric comparison of two afterloaders and treatment planning systems in vaginal high-dose-rate brachytherapy.

Purpose: In treatment planning for high-dose-rate (HDR) single-channel vaginal cylinder brachytherapy, dose distribution along the cylinder is influenced by the anisotropy of the source. Differences in anisotropy are due to differences in source dimensions and characteristics. In this study, we compared HDR vaginal cylinder brachytherapy treatment plans from two afterloader/treatment planning systems. Material and methods: Seventy-five plans with prescription to the surface were generated for cylinders in Varian BrachyVision and Elekta Oncentra. To understand the impact of source anisotropy on dose distribution to the surface of the cylinder, potential effect caused by differences in cylinder geometry between systems was eliminated by re-planning Varian cylinder using Elekta source model. Mean relative dose was calculated for each point as well as the dome and length of the cylinder. Related-samples Wilcoxon signed-rank tests were performed to compare the mean relative dose between systems. Results: Treatment plans with VariSource iX source and cylinder demonstrated 16.2% lower (p < 0.001) dose at the tip compared to Elekta v.3. Average dose to the points along the dome of cylinder was 128.4% ±17.9% prescription dose with VariSource iX source and cylinder, and 99.9% ±4.3% with Elekta v.3 source and cylinder. For the same cylinder geometry, the effect of source characteristics produced up to 36.8% difference in dose homogeneity. When cylinder types were planned with the same source, there was no significant difference in dose distribution. Conclusions: This study demonstrates that the effect of source characteristics produced up to 37% difference in dose homogeneity when comparing two afterloader/treatment planning systems, independent of cylinder geometry. This insight on variation in dose surrounding source system is imperative for dosimetry considerations. Depending on the choice of afterloader, the extent of EQD2 for tumor control versus normal tissue toxicity can vary.

A first radiotherapy application of functional bulboclitoris anatomy, a novel female sexual organ-at-risk, and organ-sparing feasibility study.

OBJECTIVE: The bulboclitoris (clitoris and vestibular bulbs) is the primary organ responsible for female sexual arousal and orgasm. Effects of radiotherapy on the bulboclitoris are unknown, as its structure/function has yet to be described in radiotherapy, and it overlaps only partially with the external genitalia structure. Our aim was to: describe bulboclitoris structure, function and delineation; compare volume of and dose delivered to the bulboclitoris vs external genitalia; and, compare bulboclitoris-sparing IMRT (BCS-IMRT) to standard IMRT (S-IMRT) to determine reoptimization feasibility. METHODS: Our expert team (anatomist, pelvic radiologist, radiation oncologist) reviewed bulboclitoris anatomy and developed contouring guidance for radiotherapy. 20 female patients with anal cancer treated with chemoradiation were analyzed. Sexual organs at risk (OARs) included the external genitalia and the bulboclitoris. Volumes, dice similarity coefficients (DSCs) and dose received using S-IMRT were compared. Plans were reoptimized using BCS-IMRT. Dose-volume histograms (DVHs) for PTVs and all OARs were compared for BCS-IMRT vs S-IMRT. RESULTS: Bulboclitoris structure, function and delineation are described herein. The bulboclitoris occupies 20cc (IQR:12-24), largely distinct from the external genitalia (DSC <0.05). BCS-IMRT was superior to S-IMRT in reducing the dose to the bulboclitoris, with the greatest reductions in V30 and V40, with no significant changes in dose to other OARs or PTV 1/V95. CONCLUSION: The bulboclitoris can be contoured on planning imaging, largely distinct from the external genitalia. Compared with S-IMRT, BCS-IMRT dramatically reduced dose to the bulboclitoris in anal cancer planning. BCS-IMRT might safely reduce sexual toxicity compared with standard approaches. ADVANCES IN KNOWLEDGE: The structure and function of the bulboclitoris, the critical primary organ responsible for female sexual arousal and orgasm, has yet to be described in the radiotherapy literature. Structure, function and delineation of the bulboclitoris are detailed, delineation and bulboclitoris-sparing IMRT were feasible, and sparing reduces the dose to the bulboclitoris nearly in half in female patients receiving IMRT for anal cancer, warranting further clinical study.

RapidPlan for Knowledge-Based Planning of Malignant Pleural Mesothelioma.

PURPOSE: Treatment planning for malignant pleural mesothelioma is a challenging task due to the relatively large size of the target and the need to spare critical organs that overlap with or are within the target volume. We aimed to develop a knowledge-based model using RapidPlan (RP) for patients with 2 intact lungs. METHODS AND MATERIALS: Data from 57 patients treated with volumetric modulated arc therapy were chosen for training the dose estimation model at a single dose level. The prescription dose was 50.4 Gy in 1.8 Gy fractions. The model was validated on 23 new patients by comparing the clinical plan to the RP. Time taken to plan the RP was compared with that for the clinical plan. RESULTS: For similar target coverage and plan inhomogeneity, RP significantly improved the sparing of the contralateral lung, heart, stomach, esophagus, and ipsilateral kidney. On average, the contralateral lung V5 Gy and V10 Gy were reduced by 13.9% (P < .001) and 7.9% (P < .001), respectively. The mean heart dose was reduced by 5 Gy (P < .001) and V30 Gy by 9.1% (P < .001). Mean dose to the stomach and esophagus were both reduced by 5 Gy (P < .001), and the ipsilateral kidney V18 Gy by 4.1% (P < .001). Mean total lung dose was reduced by 0.8 Gy with RP, which enabled an increase in prescription dose by 1 fraction Absolute volume of ipsilateral lung was adequately spared by both techniques, while sparing of all other organs, namely the cord, liver, and bowel, was not compromised with RP. Time taken with RP was 20 minutes, 45 seconds versus at least 4 hours for an experienced treatment planner. CONCLUSIONS: The RP model for malignant pleural mesothelioma showed improved sparing of critical organs with a reduced treatment planning time and increased prescription dose.

Dosimetric Correlates of Pulmonary Toxicity in Patients with Malignant Pleural Mesothelioma Receiving Radiation Therapy to the Intact Lungs.

PURPOSE: We aimed to determine dose-volume constraints that correlate with severe (grade ≥3) radiation pneumonitis (RP) in patients diagnosed with malignant pleural mesothelioma, treated using volumetric modulated arc therapy. METHODS AND MATERIALS: Data from 40 patients with malignant pleural mesothelioma who underwent pleurectomy decortication and adjuvant radiation therapy at our institution between December 2010 and October 2016 were retrospectively analyzed. Dosimetric variables for the absolute volume and percentage volume of the ipsilateral lung, contralateral lung, and heart were recorded. Events of RP were assessed using the Common Terminology Criteria for Toxicity and Adverse Events, version 4.0. The statistical analysis with Wilcoxon rank-sum, Spearman rank correlation, and receiver operating characteristic curves was computed using MATLAB V9.1, RV3.4, and SAS V9.4. RESULTS: Of the 40 patients, 26 patients (65%) were male. The median age at the time of diagnosis was 66.5 years (range, 44-84 years). The median prescription dose was 45 Gy (range, 30-54 Gy). Five patients (12.5%) had grade ≥3 RP. The incidence of grade≥ 3 RP showed a significant correlation (P < .05) with the absolute volume and percentage volume of the ipsilateral lung spared of ≥20 Gy (55 cc; 7%) and spared of ≥30 Gy (200 cc; 23%). Dosimetric variables of the contralateral lung, total lung, and heart did not show a correlation with incidence of grade ≥3 RP. CONCLUSIONS: In our cohort, sparing the ipsilateral lung of at least 55 cc of 20 Gy and 200 cc of 30 Gy correlated with a reduced incidence of severe (grade ≥3) RP.

Dose to organs in the supraclavicular region when covering the Internal Mammary Nodes (IMNs) in breast cancer patients: A comparison of Volumetric Modulated Arc Therapy (VMAT) versus 3D and VMAT.

During breast/chest wall and regional nodal irradiation (RNI), standard 3D conformal techniques can fail to meet the dosimetric constraints for the heart and ipsilateral lung. VMAT can improve the dosimetric sparing of the heart and lungs. However the unnecessary increase in dose to the organs in the supraclavicular region as a result of using VMAT can be avoided. In this work we investigate potential dosimetric advantages of combining 3D with VMAT to improve sparing of these organs. Ten breast cancer patients requiring radiation therapy to the breast/chest wall and RNI including the IMNs, and who did not have a viable 3D conformal plan were chosen for the study. Each patient was planned with VMAT and with a combination of 3D for the supraclavicular region and VMAT for the breast/chest wall followed by a dosimetric comparison. Prescription dose was 50.4 Gy in 28 fractions. For similar coverage to the PTV and IMNs, doses to the esophagus and cord were reduced by 17.8 Gy and 15.5 Gy while mean dose to the thyroid and larynx were also reduced by 16.5 Gy and 11.7 Gy respectively. Maximum brachial plexus dose was the same in both techniques. The ipsilateral lung V20Gy increased by 3.1% but was still < 30%. No significant differences were noted in doses to the heart, total lung and contralateral breast. However V5Gy to the contralateral lung was reduced by 8.5% with the combined plan. Using 3D conformal planning for the supraclavicular region and VMAT over the breast/chest wall improves sparing of the esophagus, cord, thyroid and larynx while reducing low dose exposure to the contralateral lung and does not compromise doses to the heart, ipsilateral lung and total lung.

Reduction in low-dose to normal tissue with the addition of deep inspiration breath hold (DIBH) to volumetric modulated arc therapy (VMAT) in breast cancer patients with implant reconstruction receiving regional nodal irradiation.

BACKGROUND: Despite dosimetric benefits of volumetric modulated arc therapy (VMAT) in breast cancer patients with implant reconstruction receiving regional nodal irradiation (RNI), low dose to the thoracic structures remains a concern. Our goal was to report dosimetric effects of adding deep inspiration breath hold (DIBH) to VMAT in left-sided breast cancer patients with tissue expander (TE)/permanent implant (PI) reconstruction receiving RNI. METHODS: Ten consecutive breast cancer patients with unilateral or bilateral TE/PI reconstruction who were treated with a combination of VMAT and DIBH to the left reconstructed chest wall and regional nodes were prospectively identified. Free breathing (FB) and DIBH CT scans were acquired for each patient. VMAT plans for the same arc geometry were compared for FB versus DIBH. Prescription dose was 50 Gy in 25 fractions. Dosimetric differences were tested for statistical significance. RESULTS: For comparable coverage and target dose homogeneity, the mean dose to the heart reduced on average by 2.9 Gy (8.2 to 5.3 Gy), with the addition of DIBH (p < 0.05). The maximum dose to the left anterior descending (LAD) artery was reduced by 9.9 Gy (p < 0.05), which related closely to the reduction in the maximum heart dose (9.4 Gy). V05 Gy to the heart, ipsilateral lung, contralateral lung and total lung (p < 0.05) decreased on average by 29.6%, 5.8%, 15.4% and 10.8% respectively. No significant differences were seen in the ipsilateral lung V20 Gy or mean dose as well as in the mean contralateral breast/implant dose. However, V04 Gy and V03 Gy of the contralateral breast/implant were respectively reduced by 13.2% and 18.3% using DIBH (p < 0.05). CONCLUSION: Combination of VMAT and DIBH showed significant dosimetric gains for low dose to the heart, lungs and contralateral breast/implant. Not surprisingly, the mean and maximum dose to the heart and to the LAD were also reduced. DIBH should be considered with the use of VMAT in breast cancer patients with implant reconstructions receiving RNI.

Computed tomography-based treatment planning for high-dose-rate brachytherapy using the tandem and ring applicator: influence of applicator choice on organ dose and inter-fraction adaptive planning.

Three dimensional planning for high-dose-rate (HDR) brachytherapy in cervical cancer has been highly recommended by consensus guidelines such as the American Brachytherapy Society (ABS) and the Groupe Européen de Curiethérapie - European Society for Radiotherapy and Oncology (GEC-ESTRO). In this document, we describe our experience with computed tomography (CT)-based planning using the tandem/ring applicator. We discuss the influence of applicator geometry on doses to organs at risk (OARs), namely the bladder, rectum, and sigmoid. Through example cases with dose prescribed to point A, we demonstrate how adaptive planning can help achieve constraints to the OARs as per guidelines.

Geometric dose prediction model for hemithoracic intensity-modulated radiation therapy in mesothelioma patients with two intact lungs.

The presence of two intact lungs makes it challenging to reach a tumoricidal dose with hemithoracic pleural intensity-modulated radiation therapy (IMRT) in patients with malignant pleural mesothelioma (MPM) who underwent pleurectomy/decortications or have unresectable disease. We developed an anatomy-based model to predict attainable prescription dose before starting optimization. Fifty-six clinically delivered IMRT plans were analyzed regarding correlation of prescription dose and individual and total lung volumes, planning target volume (PTV), ipsilateral normal lung volume and ratios: contralateral/ipsilateral lung (CIVR); contralateral lung/PTV (CPVR); ipsilateral lung /PTV (IPVR); ipsilateral normal lung /total lung (INTLVR); ipsilateral normal lung/PTV (INLPVR). Spearman's rank correlation and Fisher's exact test were used. Correlation between mean ipsilateral lung dose (MILD) and these volume ratios and between prescription dose and single lung mean doses were studied. The prediction models were validated in 23 subsequent MPM patients. CIVR showed the strongest correlation with dose (R=0.603,p<0.001) and accurately predicted prescription dose in the validation cases. INLPVR and MILD as well as MILD and prescription dose were significantly correlated (R=-0.784,p<0.001 and R=0.554,p<0.001, respectively) in the training and validation cases. Parameters obtainable directly from planning scan anatomy predict achievable prescription doses for hemithoracic IMRT treatment of MPM patients with two intact lungs. PACS number(s): 87.55.de, 87.55.dk.

(125)I monotherapy using D90 implant doses of 180 Gy or greater.

PURPOSE: The purpose of this study was to characterize the oncologic results and toxicity profile of patients treated with (125)I implants using the dose delivered to 90% of the gland from the dose-volume histogram (D90) of greater than 144 Gy. METHODS AND MATERIALS: From June 1995 to Feb 2005, a total of 643 patients were treated with (125)I monotherapy for T1-T2 prostate cancer with a D90 of 180 Gy or greater (median, 197 Gy; range, 180-267 Gy). Implantations were performed using a real-time ultrasound-guided seed-placement method and intraoperative dosimetry to optimize target coverage and homogeneity by using modified peripheral loading. We analyzed biochemical disease-free survival (bDFS) of 435 patients who had a minimum 2-year prostate-specific antigen follow-up (median follow-up, 6.7 years; range, 2.0-11.1 years). RESULTS: Five-year bDFS rates for the entire cohort using the American Society for Therapeutic Radiology and Oncology and Phoenix definitions were 96.9% and 96.5%, respectively. Using the Phoenix definition, 5-year bDFS rates were 97.3% for low-risk patients and 92.8% for intermediate/high-risk patients. The positive biopsy rate was 4.1%. The freedom rate from Grade 2 or higher rectal bleeding at 5 years was 88.5%. Acute urinary retention occurred in 10.7%, more commonly in patients with high pretreatment International Prostate Symptom Scores (p < 0.01). In patients who were potent before treatment, 73.4% remained potent at 5 years after implantation. CONCLUSIONS: Patients with a minimum D90 of 180 Gy had outstanding local control based on prostate-specific antigen control and biopsy data. Toxicity profiles, particularly for long-term urinary and sexual function, were excellent and showed that D90 doses of 180 Gy or greater performed using the technique described were feasible and tolerable.

Computer-aided classification of breast masses in ultrasonic B-scans using a multiparameter approach.

Classification of breast masses in ultrasonic B-scan images is undertaken using a multiparameter approach. The parameters are generated on the basis of a non-Rayleigh statistic model of the backscattered envelope from the breast tissue. They can be computed automatically with minimal clinical intervention once the location of the mass is known. A new discriminant is developed that combines these parameters linearly. It is seen that this new discriminant performs classification of masses into benign or malignant better than the classification by any one of the individual parameters. The data set studied consisted of 99 cases (70 patients with benign masses and 29 patients with malignant masses). The areas under the receiver operating characteristic (ROC) curves (Az) and statistical attributes of the areas were studied to establish the enhancement in performance. The Az value after combining all the parameters was found to be 0.8701. Upon combining this parameter with the level of suspicion (LOS) scores of a radiologist, the performance is further enhanced with an area under the (empirical) ROC of 0.94 having an operating point at a sensitivity of 0.965 and specificity of 0.87. It is suggested that this automated approach may hold promise as a means of classifying breast masses.

Classification of breast masses in ultrasonic B scans using Nakagami and K distributions.

Classification of breast masses in greyscale ultrasound images is undertaken using a multiparameter approach. Five parameters reflecting the non-Rayleigh nature of the backscattered echo were used. These parameters, based mostly on the Nakagami and K distributions, were extracted from the envelope of the echoes at the site, boundary, spiculated region and shadow of the mass. They were combined to create a linear discriminant. The performance of this discriminant for the classification of breast masses was studied using a data set consisting of 70 benign and 29 malignant cases. The Az value for the discriminant was 0.96 +/- 0.02, showing great promise in the classification of masses into benign and malignant ones. The discriminant was combined with the level of suspicion values of the radiologist leading to an Az value of 0.97 +/- 0.014. The parameters used here can be calculated with minimal clinical intervention, so the method proposed here may therefore be easily implemented in an automated fashion. These results also support the recent reports suggesting that ultrasound may help as an adjunct to mammography in breast cancer diagnostics to enhance the classification of breast masses.

ROC analysis of ultrasound tissue characterization classifiers for breast cancer diagnosis.

Breast cancer diagnosis through ultrasound tissue characterization was studied using receiver operating characteristic (ROC) analysis of combinations of acoustic features, patient age, and radiological findings. A feature fusion method was devised that operates even if only partial diagnostic data are available. The ROC methodology uses ordinal dominance theory and bootstrap resampling to evaluate A(z) and confidence intervals in simple as well as paired data analyses. The combined diagnostic feature had an A(z) of 0.96 with a confidence interval of at a significance level of 0.05. The combined features show statistically significant improvement over prebiopsy radiological findings. These results indicate that ultrasound tissue characterization, in combination with patient record and clinical findings, may greatly reduce the need to perform biopsies of benign breast lesions.