Hui-Min Ting

Dual Arc Volumetric-modulated Arc Radiotherapy (VMAT) of Nasopharyngeal Carcinomas: A Simultaneous Integrated Boost Treatment Plan Comparison with Intensity-modulated Radiotherapies and Single Arc VMAT

AIMS To compare the performance of volumetric-modulated arc radiotherapy (VMAT) by dual arc with fixed beam intensity-modulated radiotherapies (IMRTs) and single arc VMAT on nasopharyngeal carcinomas (NPC). MATERIALS AND METHODS Twenty NPC cases were re-planned using the planning system of the Pinnacle(3®)SmartArc (SA) module to compare the performance of the following four techniques: seven-field (7F) and 18-field (18F) fixed beam IMRT, and single (SA(1)) and dual arc VMAT (SA(2)). The plan was delivered on an Elekta Synergy™ Linac equipped with an 80-leaf 1cm multileaf collimator. Three dose levels of planning target volumes (PTVs) with 70/59.4/54.0Gy in 33 fractions were prescribed and delivered as a simultaneous integrated boost. The conformity index and homogeneity index of the PTVs, the comprehensive quality index (CQI), the normal tissue complication probability for the organs at risk (OARs), and the planning time, delivery efficiency and accuracy were analysed. RESULTS A significantly inferior conformity index at the three dose levels of PTV and homogeneity index of PTV(70) were observed in SA(1) compared with the other techniques. Comparable conformity index and homogeneity index of the PTV were observed among 7F/18F IMRT and SA(2). Based on the CQI of the 11 OARs, the most efficient dose reduction was observed in 18F IMRT followed in order by SA(2), 7F IMRT and SA(1). The planning time was on average 13.2/24.9/40.1/42.8min for 7F/18F IMRT/SA(1)/SA(2), respectively. With regards to the delivery efficiency compared with 7F IMRT, a 51 and 41% reduction in delivery time was achieved by SA(1) and SA(2), respectively. All techniques presented a high quality assurance pass rate (>98%) of the Γ(3mm,3%) criterion. CONCLUSION In NPC cases, SA(2) gave superior results in terms of PTV coverage and OAR sparing compared with SA(1) and approached the performance achieved by 18F IMRT, but without sacrificing the delivery efficiency.

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 (Γ3mm,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 (Γ3mm,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. PACS number: 87.53.Tf, 87.55.x, 87.55.D, 87.55.dk

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 R2, 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 R2 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.

Intensity-modulated radiotherapy for nasopharyngeal carcinoma: the reduction of radiation-induced trismus

The purpose of this study was to evaluate the degree of radiation-induced trismus after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). From 2003 to 2004, 17 non-metastatic NPC patients treated with parotid-sparing IMRT were enrolled. The maximal interincisal distance (MID) was measured to represent the maximum mouth opening. All 17 patients had both pre- and post-IMRT measurements taken, and the normalized MID (post-IMRT MID/pre-IMRT MID) was analysed to evaluate the percentage decrease in MID after IMRT. The median follow-up time was 20.5 months. One patient had nodal failure and was successfully salvaged with radiotherapy. All 17 patients were alive without cancer at the last follow-up. The average MID before IMRT was 46.2 mm (standard deviation (SD), 8.6 mm). The average MID at 12 months post-IMRT was 45.4 mm (SD, 8.9 mm). The averages of normalized MID were 94% (SD, 3.9%) at 5 months post-IMRT and 98.1% (SD, 4.2%) at 12 months post-IMRT. Based on the satisfactory preservation of normalized MID (average of 98.1% at 12 months post-IMRT), we demonstrate that IMRT reduces radiation-induced trismus in NPC patients. The recovery of normalized MID exists in the period from 5-12 months post-IMRT.

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.

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).

Dosimetric advantages of generalised equivalent uniform dose-based optimisation on dose–volume objectives in intensity-modulated radiotherapy planning for bilateral breast cancer

OBJECTIVE We compared and evaluated the differences between two models for treating bilateral breast cancer (BBC): (i) dose-volume-based intensity-modulated radiation treatment (DV plan), and (ii) dose-volume-based intensity-modulated radiotherapy with generalised equivalent uniform dose-based optimisation (DV-gEUD plan). METHODS The quality and performance of the DV plan and DV-gEUD plan using the Pinnacle(3) system (Philips, Fitchburg, WI) were evaluated and compared in 10 patients with stage T2-T4 BBC. The plans were delivered on a Varian 21EX linear accelerator (Varian Medical Systems, Milpitas, CA) equipped with a Millennium 120 leaf multileaf collimator (Varian Medical Systems). The parameters analysed included the conformity index, homogeneity index, tumour control probability of the planning target volume (PTV), the volumes V(20 Gy) and V(30 Gy) of the organs at risk (OAR, including the heart and lungs), mean dose and the normal tissue complication probability. RESULTS Both plans met the requirements for the coverage of PTV with similar conformity and homogeneity indices. However, the DV-gEUD plan had the advantage of dose sparing for OAR: the mean doses of the heart and lungs, lung V(20) (Gy), and heart V(30) (Gy) in the DV-gEUD plan were lower than those in the DV plan (p<0.05). CONCLUSIONS A better result can be obtained by starting with a DV-generated plan and then improving it by adding gEUD-based improvements to reduce the number of iterations and to improve the optimum dose distribution. Advances to knowledge The DV-gEUD plan provided superior dosimetric results for treating BBC in terms of PTV coverage and OAR sparing than the DV plan, without sacrificing the homogeneity of dose distribution in the PTV.

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.

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.