Relationships among patient characteristics, irradiation treatment planning parameters, and treatment toxicity of acute radiation dermatitis after breast hybrid intensity modulation radiation therapy.

To evaluate the relationships among patient characteristics, irradiation treatment planning parameters, and treatment toxicity of acute radiation dermatitis (RD) after breast hybrid intensity modulation radiation therapy (IMRT). The study cohort consisted of 95 breast cancer patients treated with hybrid IMRT. RD grade ≥2 (2+) toxicity was defined as clinically significant. Patient characteristics and the irradiation treatment planning parameters were used as the initial candidate factors. Prognostic factors were identified using the least absolute shrinkage and selection operator (LASSO)-based normal tissue complication probability (NTCP) model. A univariate cut-off dose NTCP model was developed to find the dose-volume limitation. Fifty-two (54.7%) of ninety-five patients experienced acute RD grade 2+ toxicity. The volume of skin receiving a dose >35 Gy (V35) was the most significant dosimetric predictor associated with RD grade 2+ toxicity. The NTCP model parameters for V35Gy were TV50 = 85.7 mL and γ50 = 0.77, where TV50 was defined as the volume corresponding to a 50% incidence of complications, and γ50 was the normalized slope of the volume-response curve. Additional potential predictive patient characteristics were energy and surgery, but the results were not statistically significant. To ensure a better quality of life and compliance for breast hybrid IMRT patients, the skin volume receiving a dose >35 Gy should be limited to <85.7 mL to keep the incidence of RD grade 2+ toxicities below 50%. To avoid RD toxicity, the volume of skin receiving a dose >35 Gy should follow sparing tolerance and the inherent patient characteristics should be considered.

Radiation-induced secondary malignancies for nasopharyngeal carcinoma: a pilot study of patients treated via IMRT or VMAT.

BACKGROUND: Patients treated with radiotherapy are at risk of developing a second cancer during their lifetime, which can directly impact treatment decision-making and patient management. The aim of this study was to qualify and compare the secondary cancer risk (SCR) after intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: We analyzed the treatment plans of a cohort of 10 NPC patients originally treated with IMRT or VMAT. Dose distributions in these plans were used to calculate the organ equivalent dose (OED) with Schneider's full model. Analyses were applied to the brain stem, spinal cord, oral cavity, pharynx, parotid glands, lung, mandible, healthy tissue, and planning target volume. RESULTS: We observed that the OED-based risks of SCR were slightly higher for the oral cavity and mandible when VMAT was used. No significant difference was found in terms of the doses to other organs, including the brain stem, parotids, pharynx, submandibular gland, lung, spinal cord, and healthy tissue. In the NPC cohort, the lungs were the organs that were most sensitive to radiation-induced cancer. CONCLUSION: VMAT afforded superior results in terms of organ-at-risk-sparing compared with IMRT. Most OED-based second cancer risks for various organs were similar when VMAT and IMRT were employed, but the risks for the oral cavity and mandible were slightly higher when VMAT was used.

Propensity-score-matched evaluation of the incidence of radiation pneumonitis and secondary cancer risk for breast cancer patients treated with IMRT/VMAT.

Propensity score matching evaluates the treatment incidence of radiation-induced pneumonitis (RP) and secondary cancer risk (SCR) after intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for breast cancer patients. Of 32 patients treated with IMRT and 58 who received VMAT were propensity matched in a 1:1 ratio. RP and SCR were evaluated as the endpoints of acute and chronic toxicity, respectively. Self-fitted normal tissue complication probability (NTCP) parameter values were used to analyze the risk of RP. SCRs were evaluated using the preferred Schneider's parameterization risk models. The dosimetric parameter of the ipsilateral lung volume receiving 40 Gy (IV40) was selected as the dominant risk factor for the RP NTCP model. The results showed that the risks of RP and NTCP, as well as that of SCR of the ipsilateral lung, were slightly lower than the values in patients treated with VMAT versus IMRT (p ≤ 0.01). However, the organ equivalent dose and excess absolute risk values in the contralateral lung and breast were slightly higher with VMAT than with IMRT (p ≤ 0.05). When compared to IMRT, VMAT is a rational radiotherapy option for breast cancer patients, based on its reduced potential for inducing secondary malignancies and RP complications.

Tennis Elbow Diagnosis Using Equivalent Uniform Voltage to Fit the Logistic and the Probit Diseased Probability Models.

To develop the logistic and the probit models to analyse electromyographic (EMG) equivalent uniform voltage- (EUV-) response for the tenderness of tennis elbow. In total, 78 hands from 39 subjects were enrolled. In this study, surface EMG (sEMG) signal is obtained by an innovative device with electrodes over forearm region. The analytical endpoint was defined as Visual Analog Score (VAS) 3+ tenderness of tennis elbow. The logistic and the probit diseased probability (DP) models were established for the VAS score and EMG absolute voltage-time histograms (AVTH). TV50 is the threshold equivalent uniform voltage predicting a 50% risk of disease. Twenty-one out of 78 samples (27%) developed VAS 3+ tenderness of tennis elbow reported by the subject and confirmed by the physician. The fitted DP parameters were TV50 = 153.0 mV (CI: 136.3-169.7 mV), γ 50 = 0.84 (CI: 0.78-0.90) and TV50 = 155.6 mV (CI: 138.9-172.4 mV), m = 0.54 (CI: 0.49-0.59) for logistic and probit models, respectively. When the EUV ≥ 153 mV, the DP of the patient is greater than 50% and vice versa. The logistic and the probit models are valuable tools to predict the DP of VAS 3+ tenderness of tennis elbow.

Normal tissue complication probability modeling for cochlea constraints to avoid causing tinnitus after head-and-neck intensity-modulated radiation therapy.

BACKGROUND: Radiation-induced tinnitus is a side effect of radiotherapy in the inner ear for cancers of the head and neck. Effective dose constraints for protecting the cochlea are under-reported. The aim of this study is to determine the cochlea dose limitation to avoid causing tinnitus after head-and-neck cancer (HNC) intensity-modulated radiation therapy (IMRT). METHODS: In total 211 patients with HNC were included; the side effects of radiotherapy were investigated for 422 inner ears in the cohort. Forty-nine of the four hundred and twenty-two samples (11.6%) developed grade 2+ tinnitus symptoms after IMRT, as diagnosed by a clinician. The Late Effects of Normal Tissues-Subjective, Objective, Management, Analytic (LENT-SOMA) criteria were used for tinnitus evaluation. The logistic and Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) models were used for the analyses. RESULTS: The NTCP-fitted parameters were TD 50 = 46.31 Gy (95% CI, 41.46-52.50), γ 50 = 1.27 (95% CI, 1.02-1.55), and TD 50 = 46.52 Gy (95% CI, 41.91-53.43), m = 0.35 (95% CI, 0.30-0.42) for the logistic and LKB models, respectively. The suggested guideline TD 20 for the tolerance dose to produce a 20% complication rate within a specific period of time was TD 20 = 33.62 Gy (95% CI, 30.15-38.27) (logistic) and TD 20 = 32.82 Gy (95% CI, 29.58-37.69) (LKB). CONCLUSIONS: To maintain the incidence of grade 2+ tinnitus toxicity <20% in IMRT, we suggest that the mean dose to the cochlea should be <32 Gy. However, models should not be extrapolated to other patient populations without further verification and should first be confirmed before clinical implementation.

Patient- and therapy-related factors associated with the incidence of xerostomia in nasopharyngeal carcinoma patients receiving parotid-sparing helical tomotherapy.

We investigated the incidence of moderate to severe patient-reported xerostomia among nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT) and identified patient- and therapy-related factors associated with acute and chronic xerostomia toxicity. The least absolute shrinkage and selection operator (LASSO) normal tissue complication probability (NTCP) models were developed using quality-of-life questionnaire datasets from 67 patients with NPC. For acute toxicity, the dosimetric factors of the mean doses to the ipsilateral submandibular gland (Dis) and the contralateral submandibular gland (Dcs) were selected as the first two significant predictors. For chronic toxicity, four predictive factors were selected: age, mean dose to the oral cavity (Doc), education, and T stage. The substantial sparing data can be used to avoid xerostomia toxicity. We suggest that the tolerance values corresponded to a 20% incidence of complications (TD20) for Dis = 39.0 Gy, Dcs = 38.4 Gy, and Doc = 32.5 Gy, respectively, when mean doses to the parotid glands met the QUANTEC 25 Gy sparing guidelines. To avoid patient-reported xerostomia toxicity, the mean doses to the parotid gland, submandibular gland, and oral cavity have to meet the sparing tolerance, although there is also a need to take inherent patient characteristics into consideration.

Developing Multivariable Normal Tissue Complication Probability Model to Predict the Incidence of Symptomatic Radiation Pneumonitis among Breast Cancer Patients.

PURPOSE: Symptomatic radiation pneumonitis (SRP), which decreases quality of life (QoL), is the most common pulmonary complication in patients receiving breast irradiation. If it occurs, acute SRP usually develops 4-12 weeks after completion of radiotherapy and presents as a dry cough, dyspnea and low-grade fever. If the incidence of SRP is reduced, not only the QoL but also the compliance of breast cancer patients may be improved. Therefore, we investigated the incidence SRP in breast cancer patients after hybrid intensity modulated radiotherapy (IMRT) to find the risk factors, which may have important effects on the risk of radiation-induced complications. METHODS: In total, 93 patients with breast cancer were evaluated. The final endpoint for acute SRP was defined as those who had density changes together with symptoms, as measured using computed tomography. The risk factors for a multivariate normal tissue complication probability model of SRP were determined using the least absolute shrinkage and selection operator (LASSO) technique. RESULTS: Five risk factors were selected using LASSO: the percentage of the ipsilateral lung volume that received more than 20-Gy (IV20), energy, age, body mass index (BMI) and T stage. Positive associations were demonstrated among the incidence of SRP, IV20, and patient age. Energy, BMI and T stage showed a negative association with the incidence of SRP. Our analyses indicate that the risk of SPR following hybrid IMRT in elderly or low-BMI breast cancer patients is increased once the percentage of the ipsilateral lung volume receiving more than 20-Gy is controlled below a limitation. CONCLUSIONS: We suggest to define a dose-volume percentage constraint of IV20< 37% (or AIV20< 310cc) for the irradiated ipsilateral lung in radiation therapy treatment planning to maintain the incidence of SPR below 20%, and pay attention to the sequelae especially in elderly or low-BMI breast cancer patients. (AIV20: the absolute ipsilateral lung volume that received more than 20 Gy (cc).

LASSO NTCP predictors for the incidence of xerostomia in patients with head and neck squamous cell carcinoma and nasopharyngeal carcinoma.

To predict the incidence of moderate-to-severe patient-reported xerostomia among head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). Multivariable normal tissue complication probability (NTCP) models were developed by using quality of life questionnaire datasets from 152 patients with HNSCC and 84 patients with NPC. The primary endpoint was defined as moderate-to-severe xerostomia after IMRT. The numbers of predictive factors for a multivariable logistic regression model were determined using the least absolute shrinkage and selection operator (LASSO) with bootstrapping technique. Four predictive models were achieved by LASSO with the smallest number of factors while preserving predictive value with higher AUC performance. For all models, the dosimetric factors for the mean dose given to the contralateral and ipsilateral parotid gland were selected as the most significant predictors. Followed by the different clinical and socio-economic factors being selected, namely age, financial status, T stage, and education for different models were chosen. The predicted incidence of xerostomia for HNSCC and NPC patients can be improved by using multivariable logistic regression models with LASSO technique. The predictive model developed in HNSCC cannot be generalized to NPC cohort treated with IMRT without validation and vice versa.

Using multivariate regression model with least absolute shrinkage and selection operator (LASSO) to predict the incidence of Xerostomia after intensity-modulated radiotherapy for head and neck cancer.

PURPOSE: The aim of this study was to develop a multivariate logistic regression model with least absolute shrinkage and selection operator (LASSO) to make valid predictions about the incidence of moderate-to-severe patient-rated xerostomia among head and neck cancer (HNC) patients treated with IMRT. METHODS AND MATERIALS: Quality of life questionnaire datasets from 206 patients with HNC were analyzed. The European Organization for Research and Treatment of Cancer QLQ-H&N35 and QLQ-C30 questionnaires were used as the endpoint evaluation. The primary endpoint (grade 3(+) xerostomia) was defined as moderate-to-severe xerostomia at 3 (XER3m) and 12 months (XER12m) after the completion of IMRT. Normal tissue complication probability (NTCP) models were developed. The optimal and suboptimal numbers of prognostic factors for a multivariate logistic regression model were determined using the LASSO with bootstrapping technique. Statistical analysis was performed using the scaled Brier score, Nagelkerke R(2), chi-squared test, Omnibus, Hosmer-Lemeshow test, and the AUC. RESULTS: Eight prognostic factors were selected by LASSO for the 3-month time point: Dmean-c, Dmean-i, age, financial status, T stage, AJCC stage, smoking, and education. Nine prognostic factors were selected for the 12-month time point: Dmean-i, education, Dmean-c, smoking, T stage, baseline xerostomia, alcohol abuse, family history, and node classification. In the selection of the suboptimal number of prognostic factors by LASSO, three suboptimal prognostic factors were fine-tuned by Hosmer-Lemeshow test and AUC, i.e., Dmean-c, Dmean-i, and age for the 3-month time point. Five suboptimal prognostic factors were also selected for the 12-month time point, i.e., Dmean-i, education, Dmean-c, smoking, and T stage. The overall performance for both time points of the NTCP model in terms of scaled Brier score, Omnibus, and Nagelkerke R(2) was satisfactory and corresponded well with the expected values. CONCLUSIONS: Multivariate NTCP models with LASSO can be used to predict patient-rated xerostomia after IMRT.

Effect of different treatment plans on irradiated small-bowel volume in gynecologic patients undergoing whole-pelvic irradiation.

To evaluate the effect of different treatment plans for whole-pelvic irradiation on small-bowel volumes (SBVs) in patients with gynecologic malignancies, 40 patients were enrolled in this study. Computed tomography (CT) simulations were performed, and the small bowel of each patient was outlined manually. Treatment plans with equal-weighted (EW) and non-equal-weighted (NEW) (70% in bilateral directions) techniques of four-field and intensity-modulated radiation therapy (IMRT) were performed. The V10-V100 represented the volume (cm³) at different levels of the prescribed doses (10-100%). The V10-V100 was compared among the different treatment planning techniques, and patients who were suitable for IMRT or NEW were identified. IMRT and NEW significantly reduced the V50-V100 and V40-V60 levels compared with EW, respectively. NEW caused a significant reduction in the V30-V60 levels in patients with a BMI ≥26 kg/m². Patients with IMRT demonstrated lower V70-V100 levels compared with those with NEW. In patients with a BMI ≥26 kg/m² or an age ≥55 years, lower V20-V50 levels were noted using NEW compared with IMRT. Treatment planning with larger weighting in the bilateral directions in four-field radiotherapy reduces the low-dose SBV in patients with gynecologic malignancies, especially in those with a high BMI or the elderly. IMRT effectively reduces high-dose SBV, especially in patients with a low BMI.

Comparative analysis of SmartArc-based dual arc volumetric-modulated arc radiotherapy (VMAT) versus intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma.

The purpose of this study was to evaluate and quantify the planning performance of SmartArc-based volumetric-modulated arc radiotherapy (VMAT) versus fixed-beam intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) using a sequential mode treatment plan. The plan quality and performance of dual arc-VMAT (DA-VMAT) using the Pinnacle3 Smart-Arc system (clinical version 9.0; Philips, Fitchburg, WI, USA) were evaluated and compared with those of seven-field (7F)-IMRT in 18 consecutive NPC patients. Analysis parameters included the conformity index (CI) and homogeneity index (HI) for the planning target volume (PTV), maximum and mean dose, normal tissue complication probability (NTCP) for the specified organs at risk (OARs), and comprehensive quality index (CQI) for an overall evaluation in the 11 OARs. Treatment delivery time, monitor units per fraction (MU/fr), and Gamma(3 mm, 3%) evaluations were also analyzed. DA-VMAT achieved similar target coverage and slightly better homogeneity than conventional 7F-IMRT with a similar CI and HI. NTCP values were only significantly lower in the left parotid gland (for xerostomia) for DA-VMAT plans. The mean value of CQI at 0.98 ± 0.02 indicated a 2% benefit in sparing OARs by DA-VMAT. The MU/fr used and average delivery times appeared to show improved efficiencies in DA-VMAT. Each technique demonstrated high accuracy in dose delivery in terms of a high-quality assurance (QA) passing rate (> 98%) of the Gamma(3 mm, 3%) criterion. The major difference between DA-VMAT and 7F-IMRT using a sequential mode for treating NPC cases appears to be improved efficiency, resulting in a faster delivery time and the use of fewer MU/fr.

Parotid-sparing intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma: preserved parotid function after IMRT on quantitative salivary scintigraphy, and comparison with historical data after conventional radiotherapy.

PURPOSE: To evaluate the parotid function after parotid-sparing intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: From March 2003 to May 2004, 16 patients with nonmetastatic NPC underwent parotid-sparing IMRT. Eight of these patients had Stage III or IV NPC based on the 1997 American Joint Committee on Cancer staging system. The post-IMRT parotid function was evaluated by quantitative salivary scintigraphy and represented by the maximal excretion ratio (MER) of the parotid gland after sialogogue stimulation. The parotid function of 16 NPC patients who were previously treated with conventional radiotherapy was reviewed as the historical control. RESULTS: In the parotid-sparing IMRT group, all 16 patients were alive and without cancer at the end of follow-up period (median, 24.2 months). The mean parotid MER was 53.5% before radiotherapy, 10.7% at 1 month post-IMRT, and 23.3% at 9 months post-IMRT. In the conventional radiotherapy group, the mean parotid MER was 0.6% at 6 to 12 months postradiotherapy. The difference was statistically significant (23.3% vs. 0.6%, p<0.001, Mann-Whitney test). In the IMRT group, the mean parotid doses ranged from 33.2 Gy to 58.8 Gy (average, 43.9 Gy). The correlation between the mean parotid dose and the percentage decrease of parotid MER at 9 months post-IMRT (dMER) was statically significant (p=0.008, Pearson correlation). CONCLUSIONS: Although the mean parotid doses are relatively high, the significant preservation of parotid function is achieved with IMRT for NPC patients. The significant correlation between mean parotid dose and parotid dMER demonstrates the dose-function relationship of the parotid gland.