C. Xie

Clinical Dosimetric Study of Three Radiotherapy Techniques for Postoperative Breast Cancer: Helical Tomotherapy, IMRT, and 3D-CRT

This paper is to investigate the dosimetric characteristics of Helical Tomotherapy (HT), step-and-shoot intensity-modulated radiation therapy (SaS-IMRT) and three-dimensional conformal radiation therapy (3D-CRT) for the postoperative breast cancer as well as their dosimetric comparison of the normal tissues. CT images of 10 postoperative patients with early stage breast cancer were transferred into HT, SaS-IMRT and 3D-CRT planning systems respectively after the target region and normal tissues were outlined by the same physician to assure the contour consistency. Each prescribed dose for three different modalities of plans was given to a total of 50 Gy in 25 fractions. Doses and irradiated volumes in heart, lungs, as well as conformity index (CI) and homogeneity index (HI) were evaluated for detailed comparison. All three plans showed appropriate coverage for the prescribed target dose in the dosimetric comparison. The CI in HT and SaS-IMRT as well as 3D-CRT was 0.68 ± 0.12, 0.58 ± 0.08 and 0.40 ± 0.08, respectively. The HI were 1.10 ± 0.03, 1.14 ± 0.02 and 1.17 ± 0.04, which appeared intergroup significant differences (p < 0.05). V5, V10, as well as V20 of the heart were smallest in 3D-CRT than HT and SaS-IMRT. V5 of the ipsilateral lung was the smallest in 3D-CRT than HT and SaS-IMRT (p < 0.05); However, V20 and V30 were smaller in HT and SaS-IMRT than 3D-CRT (p < 0.05). V5 of the contralateral lung was the smallest in 3D-CRT than other groups, with V10~V30 were basically similar in numeric values with not obvious discrepancy. Comparing with SaS-IMRT and 3D-CRT, HT technique in treating breast cancer had the best conformity and homogeneity index as well as steepest dose gradient due to its highly modulated beamlets with rotational technique. The heart volume irradiated was the smallest in conventional 3D-CRT, with SaS-IMRT was the largest among the three techniques, as expected. The volume of the contralateral lung irradiated was the smallest in 3D-CRT than other groups. V5 of the ipsilateral lung was the smallest in 3D-CRT than other two groups. V10~V30 in HT and SaS-IMRT were similar and better than 3D-CRT dosimetrically. We conclude that HT technique had advantages over SaS-IMRT and 3D-CRT based on the dosimetric comparison in this study, especially in the high dose region of ipsilateral lung, target homogeneity and dose uniformity.

Clinical observation of 73 nasopharyngeal carcinoma patients treated by helical tomotherapy: the China experience.

The preliminary short-term clinical outcome of 73 nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy at our cancer institute has been evaluated. Between September 2007 and September 2009, 73 newly diagnosed NPC patients were treated with helical tomotherapy. The distributions of clinical stages according to the UICC 2002 Staging System were: 6, 27, 24, and 16 for Stage I, IIa-b, III, and IVa-b, respectively. The prescription dose was 70–74 Gy/33F to planning gross tumor volume containing the primary tumor and positive lymph nodes, with 60–62.7 Gy/33F to high risk planning target volume, while delivering 52–56 Gy/33F to low risk planning target volume. Twenty-four patients were treated with radiation therapy as single modality, 25 with concurrent cisplatin-based chemotherapy with or without anti-EGFR monoclonal antibody therapy, and 24 with concurrent anti-EGFR monoclonal antibody therapy. Setup errors were analyzed. Side-effects were evaluated with the established RTOG/EORTC criteria. Average beam-on-time was 468.8 sec/F (396.7–696.1 sec). The setup errors in the lateral, longitudinal and vertical directions were 0.00 ± 1.79 mm, −0.55 ± 2.17 mm and 0.38 ± 1.43 mm, corresponding to 3.80 mm, 4.20 mm, and 2.46 mm as the CTV-PTV margin in these directions. The grade 0, 1, 2 and 3 acute skin toxicity was 2.7%, 76.7%, 13.8% and 6.8%; the grade 0, 1, 2 and 3 acute mucositis was 1.4%, 32.9%, 60.2% and 5.5%; and the grade 0, 1, 2 and 3 acute xerostomia was 4.0%, 45.3%, 50.7% and 0, respectively. Only 5 patients suffered from grade 3 or 4 leucopenia. Xerostomia resolved with passing of time and no grade 2 or more xerostomia was noted one year after radiation therapy. Concurrent chemotherapy significantly increased incidence of severe acute toxicities. One month after radiation therapy the remission rates of primary tumor and positive lymph nodes were 91.8% and 98.1%, respectively. The median follow-up was 14.8 months. The one-year relapse-free survival, distant metastasis-free survival and overall survival was 95.6%, 97.2% and 94.8%, respectively. In conclusion, the incidence of severe acute toxicities and late xerostomia was relatively infrequent for NPC patients treated with helical tomotherapy. The long-term clinical outcome for these patients is under investigation.

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.

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.

Association of DNA repair gene polymorphisms with the risk of radiation pneumonitis in lung cancer patients

A total of 149 lung cancer patients were recruited to receive intensity modulated radiation therapy (IMRT). The association of developing radiation pneumonitis (RP) with genetic polymorphism was evaluated. The risks of four polymorphic sites in three DNA repair related genes (ERCC1, rs116615:T354C and rs3212986:C1516A; ERCC2, rs13181:A2251C; XRCC1, rs25487:A1196G) for developing grade ≥ 2 RP were assessed respectively. It was observed that ERCC1 T354C SNP had a significant effect on the development of grade ≥ 2 RP (CT/TT vs. CC, adjusted HR = 0.517, 95% CI, 0.285–0.939; adjusted P = 0.030). It is the first time demonstrating that CT/TT genotype of ERCC1 354 was significantly associated with lower RP risk after radio therapy.

A Dosimetric Analysis of Preoperative Intensity-modulated and Image-guided Radiation Therapy with and without Simultaneous Integrated Boost for Locally Advanced Rectal Cancer

Preoperative concurrent chemoradiation, total mesorectal excision and adjuvant chemotherapy have become the standard of care for patients with locally advanced rectal cancer (LARC). Several studies have reported increased pathologic complete response rates and improved locoregional control with escalating doses of preoperative radiotherapy. In this study, we assess the dosimetric feasibility and impact of intensity-modulated and image-guided radiation therapy (IMRT-IGRT) with a simultaneous integrated boost (SIB) in preoperative chemoradiation for LARC. Ten rectal cancer patients treated with preoperative chemoradiation were enrolled in this study, and IMRT56.25Gy and IMRT50Gy plans were made for each patient with a CTV-PTV50Gy margin of 5 mm and a GTV-PTV56.25Gy margin of 10 mm adapted to daily KV cone-beam computed tomography (CBCT) imaging. In the boost group (IMRT56.25Gy), the prescribed doses were 56.25 Gy to the gross tumor (PTV56.25Gy) and 50 Gy to areas at high risk of harboring microscopic disease (PTV50Gy). Doses were delivered over 25 daily fractions using a SIB technique. In the no-boost group (IMRT50Gy), the prescribed dose was 50 Gy to PTV50Gy without a boost. The goals were to give at least 95% of the prescribed doses to at least 95% of the PTVs while keeping irradiated volumes of the organs at risk dose as low as possible. Differences in dose distributions between the two sets of plans were analyzed using a paired sample t-test. All IMRT56.25Gy plans met the needs of the prescribed doses and organ at risk dose constraints. Compared to IMRT50Gy, the addition of a SIB in IMRT56.25Gy resulted in significant increases in mean dose and V40Gy to the bladder and significant increases of V30Gy and V40Gy to femoral heads (p < 0.05 for all points). There were no significant differences in dose to small bowel or pelvic bone marrow between the two sets of plans. Preoperative IMRT-IGRT with SIB for LARC is feasible dosimetrically with respect to organ at risk dose constraints. A phase II trial to evaluate the clinical safety and efficacy of this approach is being undertaken.

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 cm3 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.

GSTP1 Ile105Val polymorphism might be associated with the risk of radiation pneumonitis among lung cancer patients in Chinese population: A prospective study

Background: Growing data suggest that DNA damage repair and detoxification pathways play crucial roles in radiation-induced toxicities. To determine whether common functional single-nucleotide polymorphisms (SNPs) in candidate genes from these pathways can be used as predictors of radiation pneumonitis (RP), we conducted a prospective study to evaluate the associations between functional SNPs and risk of RP. Methods: We recruited a total of 149 lung cancer patients who had received intensity modulated radiation therapy (IMRT). GSTP1 and XRCC1 were genotyped using the SurPlexTM-xTAG method in all patients. RP events were prospectively scored using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Kaplan-Meier analysis was used to determine the cumulative probability of RP of grade ≥ 2. Cox proportional hazard regression was performed to identify clinical variables and SNPs associated with risk of RP grade ≥ 2, using univariate and multivariate analysis, respectively. Results: With a median follow-up of 9 months, the incidence of RP of grade ≥ 2 was 38.3%. A predicting role in RP was observed for the GSTP1 SNP (adjusted hazard ratio 3.543; 95% CI 1.770-7.092; adjusted P< 0.001 for the Ile/Val and Val/Val genotypes versus Ile/Ile genotype). Whereas, we found that patients with XRCC1 399Arg/Gln and Gln/Gln genotypes had a lower risk of RP compares with those carrying Arg/Arg genotype (adjusted HR 0.653; 95% CI 0.342-1.245), but with no statistical significance observed (adjusted P = 0.195). Conclusions: Our results suggested a novel association between GSTP1 SNP 105Ile/Val and risk of RP development, which suggests the potential use of this genetic polymorphism as a predictor of RP. In addition, genetic polymorphisms of XRCC1 399Arg/Gln may also be associated with RP.

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.

SU‐E‐T‐155: RapidArc Delivery Performance Using EDR2 Film and EPID Measurement

PURPOSE The Varian RapidArc is a system for volumetric modulated arc therapy (VMAT) technique. To obtain the accuracy,efficiency and reliability of the optimal conformal dose during treatment, RapidArc delivery depends on the controlling capabilities and synchronicity such as variable dose rate, variable gantry speed and dynamic multileaf collimator(DMLC). This study describes the development and implementation EDR2 film and electronic portal imaging device(EPID) during commissioning and quality assurance procedures for RapidArc radiotherapy delivery system. METHODS The tests were designed to evaluate RapidArc performance using EDR2 film and EPID tools. The accuracy of DMLC position during gantry rotation, the ability to vary and control the dose-rate and gantry speed, the synchronization of variable DMLC speed and dose-rate were examined. RESULTS The picket fence test of MLC in stationary gantry and RapidArc modes were implemented. EDR2 film and EPID showed good consistency for obtaining the patterns, and the minimal analysis of leaf accuracy test measured with film was better than 0.4mm with EPID. The synchronicity test, a fully dynamic field, was designed to uniformly irradiate seven parts of a square field using different combinations of gantry speed and dose rate. Comparing with a corresponding open field for the influence of beam flatness and asymmetry, both EDR2 film and EPID were found to yield good results, with a mean deviation of 0.24% vs 0.19%. During evaluating accurate correlated motion of DMLC speed, gantry speed and dose-rates, the dose of four parts in a field showed good agreement, with a mean deviation of 0% vs 0.01%. The analysis of dose patterns was less than 2%. CONCLUSION This study demonstrated that EDR2 film and EPID system can be used as reliable and efficient quality assurance tools for RapidArc delivery performance. Of course, the use of VMAT QA measurement with EPID increases the efficiency of routine QA.