A dosimetric comparison of the use of equally spaced beam (ESB), beam angle optimization (BAO), and volumetric modulated arc therapy (VMAT) in head and neck cancers treated by intensity modulated radiotherapy.

INTRODUCTION: Previous studies have shown that the beam arrangement had significant influence on plan quality in intensity modulated radiotherapy (IMRT). This study aimed to evaluate the dosimetric performance of beam arrangement methods by employing equally spaced beams (ESB), beam angle optimization (BAO), and volumetric modulated arc therapy (VMAT) in the planning of five types of head and neck (H&N) cancers treated by IMRT. METHODS: Five plans of different beam arrangement methods were optimized for 119 H&N cancer patients with the prescription of 66-70 Gy for high-risk planning target volume (PTV), 60 Gy for intermediate risk PTV, 54 Gy for low-risk PTV using a simultaneously integrated boost method. The five-beam arrangement methods were: ESB, coplanar BAO (BAOc), noncoplanar BAO (BAOnc), two-arc VMAT (VMAT2), and three-arc VMAT (VMAT3). The H&N cancers included cancers of nasopharynx, oral cavity, larynx, maxillary sinus, and parotid. Although the partial arc VMAT could be used in cases where the PTVs were situated at one side of the head such as the parotid, this arrangement was not included because it was intended to include only the beam arrangements that were applicable to all the types of head and neck cancers in the study. The plans were evaluated using a "figure-of-merit" known as uncomplicated target conformity index (UTCI). In addition, PTV conformation number and homogeneity index, normal tissue integral dose, and organ at risk (OAR) doses were also used. The mean values of these parameters were compared among the five plans. RESULTS: All treatment plans met the preset dose requirements for the target volumes and OARs. For nasopharyngeal cancer, VMAT3 and BAOnc demonstrated significantly higher UTCI. For cancer of oral cavity, most beam arrangement showed similar UTCI except ESB, which was relatively lower. For cancer of larynx, there was no significant difference in UTCI among the five-beam arrangement methods. For cancers of maxillary sinus and parotid gland, the two BAO methods showed marginally higher UTCI among all the five methods. CONCLUSION: Individual methods showed dosimetric advantages on certain aspects, and the UTCI of the BAO treatment plans are marginally greater in the case of maxillary sinus and parotid gland. However, if treatment time was included into consideration, VMAT plans would be recommended for cancers of the nasopharynx, oral cavity, and larynx.

Sonographic appearance of thyroid glands in patients treated with intensity-modulated radiotherapy or conventional radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: This study aimed to investigate the sonographic appearances of the thyroid glands in nasopharyngeal carcinoma (NPC) patients whose cervical lymph nodes were treated with conventional radiotherapy (RT) or intensity-modulated radiotherapy (IMRT). The post-RT sonographic appearances of the thyroid glands in NPC patients were also correlated with the thyroid function. METHODS: One hundred and three NPC patients who had completed RT of cervical lymph nodes using the anterior cervical field, 30 NPC patients who had completed RT of cervical lymph nodes using IMRT, and 61 healthy subjects were included in the study. Thyroid glands were sonographically assessed for their size, echogenicity, vascularity, and internal architecture. Thyroid function tests were also performed on each subject. RESULTS: In comparison with the patients with abnormal thyroid function, the thyroid glands of the patients with normal thyroid function tended to be homogeneous and to have greater volume and echogenicity index (p < 0.05). Compared with those of the healthy subjects, the thyroid glands of patients previously treated with IMRT and those treated with the anterior cervical field showed significantly lower thyroid volume, lower incidence and number of nodules, and higher vascularity index (p < 0.05). CONCLUSIONS: The patient's history of previous RT should be taken into consideration in the sonographic examination of the thyroid gland post-RT. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43:210-223, 2015.

A comprehensive dosimetric evaluation of using RapidArc volumetric-modulated arc therapy for the treatment of early-stage nasopharyngeal carcinoma.

The purpose of this study was to investigate the potential benefits of using triple-arc volumetric-intensity modulated arc radiotherapy (RapidArc (RA)) for the treatment of early-stage nasopharyngeal carcinoma (NPC). A comprehensive evaluation was performed including plan quality, integral doses, and peripheral doses. Twenty cases of stage I or II NPC were selected for this study. Nine-field sliding window IMRT, double-arc, and triple-arc RA treatment plans were compared with respect to target coverage, dose conformity, critical organ sparing, and integral doses. Measurement of peripheral doses was performed using thermoluminescent dosimeters in an anthropomorphic phantom. While similar conformity and target coverage were achieved by the three types of plans, triple-arc RA produced better sparing of parotid glands and spinal cord than double-arc RA or IMRT. Double-arc RA plans produced slightly inferior parotid sparing and dose homogeneity than the other two delivery methods. The monitor units (MU) required for triple-arc were about 50% less than those of IMRT plans, while there was no significant difference in the required MUs between triple-arc and double-arc RA plans. The peripheral dose in triple-arc RA was found to be 50% less compared to IMRT near abdominal and pelvic region. Triple-arc RA improves both the plan quality and treatment efficiency compared with IMRT for the treatment of early stage NPC. It has become the preferred choice of treatment delivery method for early stage NPC at our center.

Treatment outcomes of nasopharyngeal carcinoma in modern era after intensity modulated radiotherapy (IMRT) in Hong Kong: A report of 3328 patients (HKNPCSG 1301 study).

PURPOSE: To evaluate treatment outcomes, failure patterns and late toxicities in patients with nasopharyngeal carcinoma (NPC) treated by intensity modulated radiotherapy (IMRT) in 6 public hospitals in Hong Kong over a 10-year period from 2001 to 2010. MATERIAL AND METHODS: Eligible patients were identified through the Hong Kong Cancer Registry data base. Clinical information was retrieved and verified by oncologists working in the individual centers. Treatment details, survival outcomes and late toxicities were analyzed. RESULTS: A total of 3328 patients were recruited. The median follow-up time was 80.2 months. The 8-year actuarial overall survival (OS), local failure-free survival (LFFS), regional failure-free survival (RFFS), distant failure free survival (DFFS), progression-free survival (PFS) for the whole group was 68.5%, 85.8%, 91.5%, 81.5% and 62.6% respectively. Male gender, older age, advanced T and N stage were adverse prognostic factors for OS, DFFS and PFS, whereas use of chemotherapy in form of concurrent chemo-irradiation (CRT), neoadjuvant + CRT, or CRT + adjuvant chemotherapy were favorable prognostic factors for OS and PFS. The local control was adversely affected by advanced T stage. N stage remained as the single adverse prognostic factor for regional control. Distant metastasis was the commonest site of failure. CONCLUSION: IMRT is an effective treatment for NPC with excellent overall loco-regional control. Distant metastasis is the major site of failure. Concurrent chemotherapy with cisplatin has an established role in NPC patients treated by IMRT.

Analysis of Plasma Epstein-Barr Virus DNA in Nasopharyngeal Cancer After Chemoradiation to Identify High-Risk Patients for Adjuvant Chemotherapy: A Randomized Controlled Trial.

Purpose The contribution of adjuvant chemotherapy after chemoradiation therapy (CRT) in nasopharyngeal cancer (NPC) remains controversial. Plasma Epstein-Barr virus (EBV) DNA is a potential biomarker of subclinical residual disease in NPC. In this prospective, multicenter, randomized controlled trial, we used plasma EBV DNA to identify patients with NPC at a higher risk of relapse for adjuvant chemotherapy. Patients and Methods Eligible patients with histologically confirmed NPC of Union for International Cancer Control stage IIB to IVB, adequate organ function, and no locoregional disease or distant metastasis were screened by plasma EBV DNA at 6 to 8 weeks after radiotherapy (RT). Patients with undetectable plasma EBV DNA underwent standard surveillance. Patients with detectable plasma EBV DNA were randomly assigned to either adjuvant chemotherapy with cisplatin and gemcitabine for six cycles (arm 1) or observation (arm 2). Patients were stratified for primary treatment (RT v CRT) and stage (II/III v IV). The primary end point was relapse-free survival (RFS). Results Seven hundred eighty-nine patients underwent EBV DNA screening. Plasma EBV DNA was undetectable in 573 (72.6%) and detectable in 216 (27.4%); 104 (13.2%) with detectable EBV DNA were randomly assigned to arms 1 (n = 52) and 2 (n = 52). After a median follow-up of 6.6 years, no significant difference was found in 5-year RFS rate between arms 1 and 2 (49.3% v 54.7%; P = .75; hazard ratio for relapse or death, 1.09; 95% CI, 0.63 to 1.89). The level of post-RT plasma EBV DNA correlated significantly with the hazards of locoregional failure, distant metastasis, and death. Conclusion In patients with NPC with detectable post-RT plasma EBV DNA, adjuvant chemotherapy with cisplatin and gemcitabine did not improve RFS. Post-RT plasma EBV DNA level should be incorporated as the selection factor in future clinical trials of adjuvant therapy in NPC.

Preliminary results of radiation dose escalation for locally advanced nasopharyngeal carcinoma.

PURPOSE: To study the safety and efficacy of dose escalation in tumor for locally advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: From September 2000 to June 2004, 50 patients with T3-T4 NPC were treated with intensity-modulated radiotherapy (IMRT). Fourteen patients had Stage III and 36 patients had Stage IVA-IVB disease. The prescribed dose was 76 Gy to gross tumor volume (GTV), 70 Gy to planning target volume (PTV), and 72 Gy to enlarged neck nodes (GTVn). All doses were given in 35 fractions over 7 weeks. Thirty-four patients also had concurrent cisplatin and induction or adjuvant PF (cisplatin and 5-fluorouracil). RESULTS: The average mean dose achieved in GTV, GTVn, and PTV were 79.5 Gy, 75.3 Gy, and 74.6 Gy, respectively. The median follow-up was 25 months, with 4 recurrences: 2 locoregional and 2 distant failures. All patients with recurrence had IMRT alone without chemotherapy. The 2-year locoregional control rate, distant metastases-free and disease-free survivals were 95.7%, 94.2%, and 93.1%, respectively. One treatment-related death caused by adjuvant chemotherapy occurred. The 2-year overall survival was 92.1%. CONCLUSIONS: Dose escalation to 76 Gy in tumor is feasible with T3-T4 NPC and can be combined with chemotherapy. Initial results showed good local control and survival.

Concurrent and adjuvant chemotherapy for nasopharyngeal carcinoma: a factorial study.

PURPOSE: To study the efficacy of concurrent chemoradiotherapy (CRT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Patients with Ho's stage T3 or N2/N3 NPC or neck node > or = 4 cm were eligible. Patients were randomly assigned to have radiotherapy (RT) or CRT with uracil and tegafur and to have AC or no AC after RT/CRT. AC comprised alternating cisplatin, fluorouracil, vincristine, bleomycin, and methotrexate for six cycles. There were four treatment groups: A, RT; B, CRT; C, RT and AC; D, CRT and AC. For CRT versus RT, groups B and D were compared with groups A and C. For AC versus no AC, groups C and D were compared with groups A and B. RESULTS: Three-year failure-free survival (FFS) and overall survival (OS) for CRT versus RT were 69.3% versus 57.8% and 86.5% versus 76.8%, respectively (P =.14 and.06; n = 110 v 109). Distant metastases rate (DMR) was significantly reduced with CRT (14.8% v 29.4%; P =.026). Locoregional failure rates (LRFR) were similar (20% v 27.6%; P =.39). Three-year FFS and OS for AC versus no AC were 62.5% versus 65% and 80.4% versus 83.1%, respectively (P =.83 and.69; n = 111 v 108). DMR and LRFR were not reduced with AC (P =.34 and.15, respectively). Cox model showed CRT to be a favorable prognostic factor for OS (hazard ratio, 0.42; P =.009). CONCLUSION: An improvement in OS with CRT was observed but did not achieve statistical significance. The improvement seemed to be associated with a significant reduction in DMR. AC did not improve outcome.

A new approach to computing normal tissue complication probability of an intensity-modulated radiotherapy treatment with stereotactic radiotherapy boost of nasopharyngeal carcinoma: a case study.

We attempted to develop a method to compute the normal tissue complication probability (NTCP) of various critical organs from combined intensity-modulated radiotherapy (IMRT) and stereotactic radiotherapy (SRT) boost treatment of nasopharyngeal carcinoma (NPC), with the aid of a nonlinear image registration method. The SRT's planning computed tomography (CT) of a NPC patient treated with IMRT was warped to the IMRT's planning CT using a nonlinear image registration. Because CT and dose were inherently in-register, the entire dose distribution could be deformed using the same deformation field derived from the two CT sets. Using the biologically effective dose concept and the linear-quadratic model, physical doses of IMRT and SRT were converted to a 2 Gy-per-fraction equivalent dose to facilitate dose summation. The variation of organs' maximum doses of the combined treatments between traditional maximum dose sum and the proposed method was 1.5 Gy ± 1.7 Gy. After the correction of the effect of fractionation and dose heterogeneity within each organ, NTCP of each organ of interest was computed for the combined treatments. Based on the results of this case study, it is believed that dose registration could be a method for the NTCP computation of various critical organs when different fractionation schemes of radiation therapy treatment are instituted.

Survival outcome of patients with nasopharyngeal carcinoma with first local failure: a study by the Hong Kong Nasopharyngeal Carcinoma Study Group.

BACKGROUND: The purpose of this article is to report the overall survival (OS) outcome of patients with nasopharyngeal carcinoma (NPC) with local failure who received salvage treatment and to identify prognostic factors for OS. METHODS: Between January 1996 and December 2000, 2915 patients received primary radiotherapy (RT) with or without chemotherapy for nonmetastatic NPC. At a median follow-up of 3.1 years, 319 patients had developed local failure as the first failure, with or without synchronous regional/distant failure. OS was calculated from the start of primary RT. Univariate and multivariate analyses were performed to identify prognostic factors for OS in patients with isolated local failure. RESULTS: The T classification distribution of the local failure (rT classification) was as follows: 68 (21%) rT1 to T2a, 92 (29%) rT2b, 82 (26%) rT3, and 77 (24%) rT4. The rT classification was the same as the initial T classification in 82% of patients. Two hundred seventy-five patients (86%) had isolated local failure, and 232 (84%) of them did not have any distant metastasis or regional failure develop during follow-up. Salvage treatment was given to 200 patients (73%) with isolated local failure. One hundred fifty-nine patients (80%) received reirradiation (108 external beam RT [EBRT], 44 brachytherapy, and seven EBRT plus brachytherapy), 22 patients (11%) underwent nasopharyngectomy with or without postoperative RT, and 19 patients (9%) were treated with chemotherapy alone. Four patients died of RT complications, and one died of chemotherapy toxicity in the absence of active NPC. The 3-year actuarial OS for patients with isolated local failure was 74%. On multivariate analysis, advanced initial T classification (hazard ratio [HR], 1.44; p = .0006) and the use of salvage treatment (HR, 0.54; p = .0038) were independent prognostic factors. For the subgroups of patients who had the same recurrent and initial T classification, salvage treatment was associated with improved OS only in the subgroup with T1 to T2 local failure (n = 127; p = 0.0446), but not in the subgroups with T3 (n = 48) or T4 (n = 54) disease. CONCLUSIONS: Most patients with first local failure have localized disease. Salvage treatment is feasible in most of the patients with clinically isolated local failure. Patients who had early initial T classification have a more favorable prognosis. Subgroup analysis suggests that salvage treatment only prolongs survival in patients with T1 to T2 recurrent disease.

Treatment outcome for synchronous locoregional failures of nasopharyngeal carcinoma.

BACKGROUND: To review the outcome and evaluate the prognostic factors in the treatment of synchronous locoregional failures of nasopharyngeal carcinoma (NPC). METHODS: We reviewed the records of 43 patients with synchronous locoregional failures of NPC who received salvage treatment or chemotherapy between November 1986 and January 2001. The recurrent disease was stage II in 61%, stage III in 30%, and stage IV in 9%. The local disease was rT1-2 in 67% and rT3-4 in 33%, and the regional disease was rN1 in 91% and rN2 in 9%. Persistent disease, defined as failures within 4 months of completion of primary radiotherapy, occurred in 53.5% and recurrent disease in 46.5%. Seventeen patients received surgery for regional and/or local failures with or without combined radiotherapy (ST group), 14 patients received reirradiation to both local and regional disease (RT group), and 12 patients received palliative chemotherapy only (CT group). The median follow-up was 18 months (range, 4-153) and for the surviving patients it was 29 months (range, 6-153). RESULTS: The 3-year relapse-free survival (RFS) rate and disease-specific survival (DSS) rate after salvage treatment or chemotherapy were 17% and 38%, respectively. The 3-year RFS rates in stage II, III, and IV disease were 25%, 8%, and 0%, respectively. The corresponding 3-year DSS rates were 43%, 28%, and 38%. The 3-year RFS rates in the ST, RT, and CT group were 39%, 7%, and 0%, respectively. The corresponding 3-year DSS rates were 55%, 25%, and 25%. Patients whose local disease was treated by surgical resection had a 3-year local control rate of 71% compared with 38% by reirradiation using brachytherapy or external radiotherapy. For regional disease, the 3-year nodal control rate after radical neck dissection was 65% compared with 24% by reirradiation. Further locoregional failure represents the major failure pattern, and the proportion of patients who had further local, regional, and both locoregional failures were 16%, 9%, and 53%, respectively. Distant metastasis occurred in 30% of patients, and only 5% had isolated distant metastasis in the absence of locoregional failures. On multivariate analysis, treatment by reirradiation or chemotherapy alone and rN2 disease were independent factors that predicted poor survival, whereas treatment by reirradiation or chemotherapy alone was the only independent factor that predicted further relapse or failure. CONCLUSIONS: Proper selection of patients for aggressive salvage treatment and individualization of treatment are important in managing patients with synchronous locoregional failures of NPC. A significant proportion of patients with early stage locoregional failures can still achieve long-term disease control and survival after aggressive salvage treatment using surgery with or without combined radiotherapy. In patients with more advanced disease, treatment by reirradiation alone or palliative chemotherapy is largely ineffective and is associated with a poor outcome.

Intensity-modulated radiotherapy for early-stage nasopharyngeal carcinoma: a prospective study on disease control and preservation of salivary function.

BACKGROUND: Xerostomia is a uniform complication after radiotherapy (RT) for nasopharyngeal carcinoma (NPC). Dosimetric studies suggested that intensity-modulated RT (IMRT) can spare part of the parotid glands from high-dose radiation. Disease control and salivary function after IMRT for early-stage NPC was studied prospectively. METHODS: Thirty-three patients with T1,N0-N1,M0 NPC were treated with IMRT from 2000 to 2002. The prescribed dose was 68-70 grays (Gy) in 34 fractions to gross tumor volume, 64-68 Gy to the planning target volume, and 70 Gy to enlarged cervical lymph nodes. Nineteen patients had stimulated whole salivary (SWS) flow assessment and stimulated parotid salivary (SPS) flow assessment at baseline and at 2 months, 6 months, 12 months, 18 months, and 24 months after the completion of IMRT. RESULTS: At a median follow-up of 2 years, only 1 neck failure was observed. The 2-year and 3-year local control, distant metastases-free, and overall survival rates all were 100%. The lymph node control and progression-free survival rates were 100% at 2 years and 92.3% at 3 years, respectively. The average mean dose to the parotid gland was 38.8 Gy. The SWS and SPS flow showed continuous recovery: 60% and 47.1% of patients recovered at least 25% of their baseline SPS flow and SWS flow, respectively, at 1 year after completion of IMRT, and the proportions rose to 85.7% and 71.4%, respectively, by 2 years. The pH and buffering capacity of saliva also improved with time. CONCLUSIONS: Parotid-sparing IMRT achieved good locoregional control, and there was continuous recovery of salivary flow, pH, and buffering capacity in the first 2 years after IMRT in patients with NPC.