Propensity score matching analysis of a phase II study on simultaneous modulated accelerated radiation therapy using helical tomotherapy for nasopharyngeal carcinomas.

BACKGROUND: Using propensity score matching method (PSM) to evaluate the feasibility and clinical outcomes of simultaneous modulated accelerated radiation therapy (SMART) using helical tomotherapy (HT) in patients with nasopharyngeal carcinoma (NPC). METHODS: Between August 2007 and January 2016, 381 newly diagnosed NPC patients using HT were enrolled in pre-PSM cohort, including 161 cases in a prospective phase II study (P67.5 study, with a prescription dose of 67.5Gy in 30 fractions to the primary tumour and positive lymph nodes) and 220 cases in a retrospective study (P70 study, with a prescription dose of 70Gy in 33 fractions to the primary tumour and positive lymph nodes). Acute and late toxicities were assessed according to the established RTOG/EORTC criteria and Common Terminology Criteria for Adverse Events (CTCAE) V 3.0. Survival rate were assessed with Kaplan-Meier method, log-rank test and Cox regression. RESULTS: After matching, 148 sub-pairs of 296 patients were generated in post-PSM cohort. The incidence of grade 3-4 leukopenia, thrombocytopenia and anemia in the P67.5 group was significantly higher than in the P70 study, but no significant different was found in other acute toxicities or late toxicities between the two groups. The median follow-up was 33 months in the P67.5 and P70 group, ranging 12-54 months and 6-58 months, respectively. No significant differences in 3-year local-regional recurrence free survival (LRRFS), distant metastasis-free survival (DMFS), disease free survival (DFS) and overall survival (OS) were observed between the 2 groups. Univariate analysis showed that age, T stage, clinical stage were the main factors effecting survival. Cox proportional hazards model showed that 67.5Gy/30F pattern seemed superior in 3-year OS (HR = 0.476, 95% CI: 0.236-0.957). CONCLUSIONS: Through increasing fraction dose and shortening treatment time, the P67.5 study achieved excellent short-term outcomes and potential clinical benefits, with acceptable acute and late toxicities. TRIAL REGISTRATION: The trial was registered at Chinese Clinical Trial Registry on 5 July 2014 with a registration code of ChiCTRONC-14,004,895.

Treatment of nasopharyngeal carcinoma using simultaneous modulated accelerated radiation therapy via helical tomotherapy: a phase II study.

BACKGROUND: The aim of the study was to evaluate short-term safety and efficacy of simultaneous modulated accelerated radiation therapy (SMART) delivered via helical tomotherapy in patients with nasopharyngeal carcinoma (NPC). METHODS: Between August 2011 and September 2013, 132 newly diagnosed NPC patients were enrolled for a prospective phase II study. The prescription doses delivered to the gross tumor volume (pGTVnx) and positive lymph nodes (pGTVnd), the high risk planning target volume (PTV1), and the low risk planning target volume (PTV2), were 67.5 Gy (2.25 Gy/F), 60 Gy (2.0 Gy/F), and 54 Gy (1.8 Gy/F), in 30 fractions, respectively. Acute toxicities were evaluated according to the established RTOG/EORTC criteria. This group of patients was compared with the 190 patients in the retrospective P70 study, who were treated between September 2004 and August 2009 with helical tomotherapy, with a dose of 70-74 Gy/33F/6.5W delivered to pGTVnx and pGTVnd. RESULTS: The median follow-up was 23.7 (12-38) months. Acute radiation related side-effects were mainly problems graded as 1 or 2. Only a small number of patients suffered from grade 4 leucopenia (4.5%) or thrombocytopenia (2.3%). The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), local-nodal relapse-free survival (LNRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.7%, 95.5%, 92.2%, 92.7% and 93.2%, at 2 years, respectively, with no significant difference compared with the P70 study. CONCLUSIONS: Smart delivered via the helical tomotherapy technique appears to be associated with an acceptable acute toxicity profile and favorable short-term outcomes for patients with NPC. Long-term toxicities and patient outcomes are under investigation.

Hypofractionated Helical Tomotherapy for Older Aged Patients With Prostate Cancer: Preliminary Results of a Phase I-II Trial.

In our center, the feasibility and related acute toxicities of hypofractionated helical tomotherapy have been evaluated in older aged patients with prostate cancer . Between February 2009 and February 2014, 67 patients (older than 65 years) were enrolled in a prospective phase I-II study (registered number, ChiCTR-ONC-13004037). Patients in cohort 1 (n = 33) and cohort 2 (n = 34) received 76 Gy in 34 fractions (2.25 Gy/F) and 71.6 Gy in 28 fractions (2.65 Gy/F), respectively, to the prostate and seminal vesicles, while 25 patients in cohort 2 also received integrated elective lymph node irradiation (50.4 Gy). All patients were treated with helical tomotherapy, and daily image guidance was performed before each treatment. Acute toxicities were assessed with Radiation Therapy Oncology Group (RTOG)/European Organization for Research on Treatment of Cancer (EORTC) criteria. No significant difference was detected between the 2 cohorts in the incidence of acute toxicities. In cohort 1, the incidences of grade 1 and 2 genitourinary and gastrointestinal toxicities were 45.5% and 45.4%, respectively, and without grade 3 and 4 toxicities. In cohort 2, the incidences of acute grade 1 and 2 genitourinary and gastrointestinal toxicities were 47.1% and 55.9%, respectively, and grade 3 genitourinary toxicity (hematuria) was noted only in 1 patient. No significant difference was detected in the incidence of acute toxicities between the patients receiving integrated elective lymph node irradiation and those receiving irradiation to prostate and seminal vesicle in cohort 2. Univariate and multivariate analyses were performed with clinical parameters. Only the baseline weight was found negatively correlated with genitourinary toxicities at a weak level (relative risk = 0.946, 95% confidence interval 0.896-0.998], P = .043). This study shows that 2 hypofractionation regimens (76 Gy/34F and 71.6 Gy/28F) delivered with HT are well tolerated in older aged patients having prostate cancer without significant difference for acute toxicities between the 2 cohorts. Late toxicities and treatment outcomes for these patients are under investigation.

Actual anatomical and dosimetric changes of parotid glands in nasopharyngeal carcinoma patients during intensity modulated radiation therapy.

The goal of this study was to evaluate the actual anatomical and dosimetric changes of parotid glands in nasopharyngeal carcinoma patients during intensity modulated radiation therapy. With helical tomotherapy, its planning system, and adaptive software, weekly anatomical and dosimetric changes of parotid glands in 35 NPC patients were evaluated. Interweekly parotid volume varied significantly (P < 0.03). The rate of volume change reached the highest level at the 16th fraction. The average V 1 increased by 32.2 (left) and 28.6 (right), and the average D 50 increased by 33.9 (left) and 24.93 (right), respectively. Repeat data comparison indicated that the V 1 and D 50 varied significantly among different fractions (both with P = 0.000). The variation of parotid volume was inversely correlated with that of the V 1 and D 50 (both with P = 0.000). In conclusion, parotid volume and actual dose vary significantly in NPC patients during IMRT. Replanning at the end of the fourth week of IMRT may have clinical benefits.

Replanning Criteria and Timing Definition for Parotid Protection-Based Adaptive Radiation Therapy in Nasopharyngeal Carcinoma.

The goal of this study was to evaluate real-time volumetric and dosimetric changes of the parotid gland so as to determine replanning criteria and timing for parotid protection-based adaptive radiation therapy in nasopharyngeal carcinoma. Fifty NPC patients were treated with helical tomotherapy; volumetric and dosimetric (D mean, V 1, and D 50) changes of the parotid gland at the 1st, 6th, 11th, 16th, 21st, 26th, 31st, and 33rd fractions were evaluated. The clinical parameters affecting these changes were studied by analyses of variance methods for repeated measures. Factors influencing the actual parotid dose were analyzed by a multivariate logistic regression model. The cut-off values predicting parotid overdose were developed from receiver operating characteristic curves and judged by combining them with a diagnostic test consistency check. The median absolute value and percentage of parotid volume reduction were 19.51 cm(3) and 35%, respectively. The interweekly parotid volume varied significantly (p < 0.05). The parotid D mean, V 1, and D 50 increased by 22.13%, 39.42%, and 48.45%, respectively. The actual parotid dose increased by an average of 11.38% at the end of radiation therapy. Initial parotid volume, initial parotid D mean, and weight loss rate are valuable indicators for parotid protection-based replanning.

Clinical study of nasopharyngeal carcinoma treated by helical tomotherapy in China: 5-year outcomes.

BACKGROUND: To evaluate the outcomes of nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT). METHODS: Between September 2007 and August 2012, 190 newly diagnosed NPC patients were treated with HT. Thirty-one patients were treated with radiation therapy as single modality, 129 with additional cisplatin-based chemotherapy with or without anti-EGFR monoclonal antibody therapy, and 30 with concurrent anti-EGFR monoclonal antibody therapy. RESULTS: Acute radiation related side effects were mainly grade 1 or 2. Grade 3 and greater toxicities were rarely noted. The median followup was 32 (3-38) months. The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were 96.1%, 98.2%, 92.0%, and 86.3%, respectively, at 3 years. Cox multivariate regression analysis showed that age and T stage were independent predictors for 3-year OS. CONCLUSIONS: Helical tomotherapy for NPC patients achieved excellent 3-year locoregional control, distant metastasis-free survival, and overall survival, with relatively minor acute and late toxicities. Age and T stage were the main prognosis factors.

Clinical study on the changes of the tumor target volume and organs at risk in helical tomotherapy for nasopharyngeal carcinoma.

BACKGROUND: Helical tomotherapy (HT) is a new image-guided intensity-modulated radiation therapy (IMRT). The aim of this study was to evaluate the changes in the target volume and organs at risk (OARs) of patients with nasopharyngeal carcinoma (NPC) during helical tomotherapy. METHODS: Forty-three patients with NPC and treated via HT from March 2008 to January 2010 were reviewed retrospectively. Repeated CT scanning and plan adaptation were conducted at the 20th fraction during radiotherapy. The volumetric differences between the two scans were evaluated for nasopharyngeal tumor and retro-pharyngeal lymph nodes (GTVnx), neck lymph nodes (GTVnd), and parotid glands, as well as the axial diameter of the head. RESULTS: The median interval between the two scans was 25 days (23 - 28 days). The volumetric decrease in GTVnx was 30.1% (median, 29.8%) and in GTVnd 41.6% (median, 45.9%). The variation in the GTVnd volume was correlated with the weight loss of the patient. The volume of the left parotid gland decreased by 35.5% (median, 33.4%) and of the right parotid glands decreased by 36.8% (median, 33.5%). The axial diameter of the head decreased by 9.39% (median, 9.1%). CONCLUSIONS: The target volume and OARs of patients with NPC varied considerably during HT. These changes may have potential dosimetric effects on the target volume and/or OARs and influence the clinical outcome. Repeated CT scanning and replanning during the HT for NPC patients with a large target volume or an obvious weight loss are recommended.

Dosimetric comparison between helical tomotherapy and intensity-modulated radiation therapy plans for non-small cell lung cancer.

BACKGROUND: Helical tomotherapy (HT) is a new image-guided intensity-modulated radiation therapy (IMRT) technique. It is reported that HT plan for non-small-cell lung cancer (NSCLC) can give better dose uniformity, dose gradients, and protection for the lung than IMRT plan. We compared the dosimetric characteristics of HT for NSCLC with those of conventional IMRT to observe the superiority of HT. METHODS: There was a comparative case series comprising 10 patients with NSCLC. Computed tomographic (CT) images of delineated targets were transferred to the PrecisePlan planning system (IMRT) and Tomo planning system (HT). The prescription doses were 70 Gy/33F for the gross tumor volume (GTV) and the visible lymph nodes (GTVnd), and 60 Gy/33F for the clinical target volume (CTV) and the clinical target volume of the visible lymph nodes (CTVnd). The dose restrictions for organs at risk were as follows: the maximum dose to spinal cord ≤ 45 Gy, V20 to the total lungs < 30%, V50 to the heart < 50%, and V55 to the esophagus < 50%. Both plans were evaluated by means of the dose coverage of the targets, dose-volume histograms (DVHs), and other dosimetric indices. RESULTS: The dose coverage, conformity, and homogeneity of the targets' volumes were found to be satisfactory in both plans, but the homogeneity of the HT plan was better than that of IMRT. The high-dose radiation volume (V20-V30) to the lung and the mean lung dose (MLD) decreased (P < 0.05), but the low-dose radiation volume (V5-V10) increased slightly in the HT plan (P > 0.05). The maximum doses to the spinal cord, heart, esophagus and trachea in the HT plan were lower than those in the IMRT plan, but the differences were not statistically significant. CONCLUSIONS: The HT plan provids better dose uniformity, dose gradients, and protection for the organs at risk. It can reduce the high-dose radiation volume for lung and the MLD, but may deliver a larger lung volume of low-dose radiation.

[Assessment of parotid gland dose variations by helical tomotherapy adaptive system in head and neck cancer].

The paper introduces a helical tomotherapy (HT) adaptive system in assessment of parotid gland dose variation in head and neck cancer. The system, which helical therapy unit is equipped with, is based on megavoltage computed tomography (MVCT) images to calculate the actual volume and dose of region of interest (ROI). Whether to change plan is judged on the fact for the realization of adaptive radiotherapy. One case of nasopharyngeal carcinoma was as a sample to evaluate parotid gland dose variation during the treatment. On every week and last time, patient was scanned by MVCT before treatment, a total of eight MVCT images. As the treatment progressed, the parotid gland volume was shrinking and the dose was increasing. The parotids volume variation was negatively related with D50 and V1 (both P < 0.05).

[Dosimetric comparison between helical tomotherapy and step-and-shoot intensity modulated radiation therapy for endometrial carcinoma].

BACKGROUND AND OBJECTIVE: Helical tomotherapy (HT) has shown its dosimetric advantages in the radiotherapy for many cancers. To date, no published studies have performed a dosimetric evaluation of whole pelvic radiotherapy (WPRT) using HT for postoperative endometrial cancer. This study was to compare the dosimetric characteristics of HT and step-and-shoot intensity modulated radiation therapy (SaS-IMRT) for endometrial cancer patients undergoing postoperative WPRT, and to explore whether whole pelvic HT for postoperative endometrial cancer has the advantage of dosimetry. METHODS: Ten patients with endometrial cancer undergoing postoperative WPRT were enrolled in this study. SaS-IMRT and HT Plans were developed for each patient. The dose distributions of the targets, organs at risk and normal tissue were analyzed and compared. RESULTS: The mean PTV100 were 95.6% and 95.8% (P=0.72) for the SaS-IMRT and HT plans, respectively. The mean homogeneity indexes were 1.10 and 1. 07 (P=0.00). The mean conformity indexes were both 0.87. The mean doses to rectum and bladder for HT were decreased by 1.3 Gy and 3.0 Gy compared with SaS-IMRT, respectively, while the mean dose to pelvic bones was increased by 1.1 Gy. The volumes of small intestine and colon, pelvic bones receiving moderate and low dose also increased. The V5, V10 and V20 of normal tissue were increased by 13.0%, 18.0%, and 5.0% (P=0.00). The mean dose to normal tissue was increased by 2.5 Gy (P=0.00). CONCLUSIONS: Compared with SaS-IMRT, HT resulted in more homogeneous PTV dose distribution, better sparing of rectum and bladder. The volumes of small intestine and colon, pelvic bones and normal tissue receiving moderate and low dose for HT increased. The clinical significance of the dosimetric differences needs further investigations.

[Measurement and analysis of the imaging dose with megavoltage computed tomography for helical tomotherapy].

BACKGROUND & OBJECTIVE: During the helical tomotherapy process, megavoltage computed tomography (MVCT) images are usually used for guiding the precise setup of patients before/after treatment delivery, which would certainly increase the total dose for patients. This study was to investigate the imaging dose of MVCT using the body and head phantom on a tomotherapy machine. METHODS: A set of cylindrical body and head phantoms was adopted for scanning with different pitch values (1.0/2.0/3.0), lengths (4.8/7.2/9.6/12/14.4 cm) and patient setups on the couch of tomotherapy system. The average MVCT imaging doses were measured using A1SL chambers inserted in the phantoms with preset geometry. The dose uniformity was qualitatively analyzed. RESULTS: The MVCT scanning dose for the body phantom was between 0.599 and 2.876 cGy during each treatment delivery, while the dose for the head phantom was between 0.913 and 3.231 cGy. Two major parameters, the assigned pitch numbers and scanning lengths, were the most important impacts to the dose variation. The MVCT dose was inversely proportional to the CT pitch value. With respect to the scanning length, the doses responded differently along the radial direction of the phantoms with different setup criteria. CONCLUSION: The results may provide a reliable guidance for proper planning design of the scanning region, which is valuable to help minimize the extra doses to patient.