Impact of geometric uncertainties on dose distribution during intensity modulated radiotherapy of head-and-neck cancer: the need for a planning target volume and a planning organ-at-risk volume

We assessed the effect of geometric uncertainties on target coverage and on dose to the organs at risk (OARS) during intensity-modulated radiotherapy (IMRT) for head-and-neck cancer, and we estimated the required margins for the planning target volume (PTV) and the planning organ-at-risk volume (PRV). For eight head-and-neck cancer patients, we generated IMRT plans with localization uncertainty margins of 0 mm, 2.5 mm, and 5.0 mm. The beam intensities were then applied on repeat computed tomography (CT) scans obtained weekly during treatment, and dose distributions were recalculated.The dose-volume histogram analysis for the repeat ct scans showed that target coverage was adequate (V(100) >/= 95%) for only 12.5% of the gross tumour volumes, 54.3% of the upper-neck clinical target volumes (CTVS), and 27.4% of the lower-neck CTVS when no margins were added for PTV. The use of 2.5-mm and 5.0-mm margins significantly improved target coverage, but the mean dose to the contralateral parotid increased from 25.9 Gy to 29.2 Gy. Maximum dose to the spinal cord was above limit in 57.7%, 34.6%, and 15.4% of cases when 0-mm, 2.5-mm, and 5.0-mm margins (respectively) were used for prv.Significant deviations from the prescribed dose can occur during IMRT treatment delivery for head-and-neck cancer. The use of 2.5-mm to 5.0-mm margins for PTV and PRV greatly reduces the risk of underdosing targets and of overdosing the spinal cord.     

Three-dimensional conformal radiotherapy for locally advanced (Stage II and worse) head-and-neck cancer: dosimetric and clinical evaluation

PURPOSE: To evaluate the dosimetric parameters of three-dimensional conformal radiotherapy (3D-CRT) in locally advanced head-and-neck tumors (Stage II and above) and the effects on xerostomia. METHODS AND MATERIALS: A total of 49 patients with histologically proven squamous cell cancer of the head and neck were consecutively treated with 3D-CRT using a one-point setup technique; 17 had larynx cancer, 12 oropharynx, 12 oral cavity, and 6 nasopharynx cancer; 2 had other sites of cancer. Of the 49 patients, 41 received postoperative RT and 8 definitive treatment. Also, 13 were treated with cisplatin-based chemotherapy before and during RT; in 6 cases, 5-fluorouracil was added. The follow-up time was 484-567 days (median, 530 days). RESULTS: One-point setup can deliver 96% of the prescribed dose to the isocenter, to the whole planning target volume, including all node levels of the neck and without overdosages. The mean dose to the primary planning target volume was 49.54 +/- 4.82 Gy (51.53 +/- 5.47 Gy for larynx cases). The average dose to the contralateral parotid gland was approximately 38 Gy (30 Gy for larynx cases). The maximal dose to the spinal cord was 46 Gy. A Grade 0 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer xerostomia score corresponded to a mean dose of 30 Gy to one parotid gland. A lower xerostomia score with a lower mean parotid dose and longer follow-up seemed to give rise to a sort of functional recovery phenomenon. CONCLUSION: Three dimensional-CRT in head-and-neck cancers permits good coverage of the planning target volume with about 10-11 segments and one isocenter. With a mean dose of approximately 30 Gy to the contralateral parotid, we observed no or mild xerostomia.     

Dosimetric evaluation of an ipsilateral intensity modulated radiotherapy beam arrangement for parotid malignancies

Background

We conducted a dosimetric comparison of an ipsilateral beam arrangement for intensity modulated radiotherapy (IMRT) with off-axis beams.

Patients and methods

Six patients who received post-operative radiotherapy (RT) for parotid malignancies were used in this dosimetric study. Four treatment plans were created for each CT data set (24 plans): 1) ipsilateral 4-field off-axis IMRT (4fld-OA), 2) conventional wedge pair (WP), 3) 7 field co-planar IMRT (7fld), and 4) ipsilateral co-planar 4-field quartet IMRT (4fld-CP). Dose, volume statistics for the planning target volumes (PTVs) and planning risk volumes (PRVs) were compared for the four treatment techniques.

Results

Wedge pair plans inadequately covered the deep aspect of the PTV. The 7-field IMRT plans delivered the largest low dose volumes to normal tissues. Mean dose to the contralateral parotid was highest for 7 field IMRT. Mean dose to the contralateral submandibular gland was highest for 7 field IMRT and WP. 7 field IMRT plans had the highest dose to the oral cavity. The mean doses to the brainstem, spinal cord, ipsilateral temporal lobe, cerrebellum and ipsilateral cochlea were similar among the four techniques.

Conclusions

For postoperative treatment of the parotid bed, 4-field ipsilateral IMRT techniques provided excellent coverage while maximally sparing the contralateral parotid gland and submandibular gland.     

The role of intensity-modulated radiotherapy in the treatment of parotid tumors

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) treatment plans with three-dimensional conformal radiotherapy (3D-CRT) plans to investigate the suitability of IMRT for the treatment of tumors of the parotid gland. METHODS AND MATERIALS: One 3D-CRT treatment plan and 10 IMRT treatment plans with differing beam arrangements were produced for each of nine patient data sets. The plans were compared using regret analysis, dose conformity, dose to organs at risk, and uncomplicated tumor control probability (UTCP). RESULTS: The target dose was comparable in the 3D-CRT and IMRT plans, although improvements were seen when seven and nine IMRT fields were used. IMRT reduced the mean dose to the contralateral parotid gland and the maximum doses to the brain and the spinal cord, but increased the ipsilateral lens dose in some cases. Each IMRT arrangement produced a higher UTCP than the 3D-CRT plans; the largest absolute difference was 9.6%. CONCLUSIONS: IMRT is a suitable means for treating cancer of the parotid, and a five-field class solution is proposed. It produced substantial sparing of organs at risk and higher UTCPs than 3D-CRT and should enable dose escalation.     

Effect of patient setup errors on simultaneously integrated boost head and neck IMRT treatment plans

PURPOSE: The purpose of this study is to determine dose delivery errors that could result from random and systematic setup errors for head-and-neck patients treated using the simultaneous integrated boost (SIB)-intensity-modulated radiation therapy (IMRT) technique. METHODS AND MATERIALS: Twenty-four patients who participated in an intramural Phase I/II parotid-sparing IMRT dose-escalation protocol using the SIB treatment technique had their dose distributions reevaluated to assess the impact of random and systematic setup errors. The dosimetric effect of random setup error was simulated by convolving the two-dimensional fluence distribution of each beam with the random setup error probability density distribution. Random setup errors of sigma = 1, 3, and 5 mm were simulated. Systematic setup errors were simulated by randomly shifting the patient isocenter along each of the three Cartesian axes, with each shift selected from a normal distribution. Systematic setup error distributions with Sigma = 1.5 and 3.0 mm along each axis were simulated. Combined systematic and random setup errors were simulated for sigma = Sigma = 1.5 and 3.0 mm along each axis. For each dose calculation, the gross tumor volume (GTV) received by 98% of the volume (D(98)), clinical target volume (CTV) D(90), nodes D(90), cord D(2), and parotid D(50) and parotid mean dose were evaluated with respect to the plan used for treatment for the structure dose and for an effective planning target volume (PTV) with a 3-mm margin. RESULTS: Simultaneous integrated boost-IMRT head-and-neck treatment plans were found to be less sensitive to random setup errors than to systematic setup errors. For random-only errors, errors exceeded 3% only when the random setup error sigma exceeded 3 mm. Simulated systematic setup errors with Sigma = 1.5 mm resulted in approximately 10% of plan having more than a 3% dose error, whereas a Sigma = 3.0 mm resulted in half of the plans having more than a 3% dose error and 28% with a 5% dose error. Combined random and systematic dose errors with sigma = Sigma = 3.0 mm resulted in more than 50% of plans having at least a 3% dose error and 38% of the plans having at least a 5% dose error. Evaluation with respect to a 3-mm expanded PTV reduced the observed dose deviations greater than 5% for the sigma = Sigma = 3.0 mm simulations to 5.4% of the plans simulated. CONCLUSIONS: Head-and-neck SIB-IMRT dosimetric accuracy would benefit from methods to reduce patient systematic setup errors. When GTV, CTV, or nodal volumes are used for dose evaluation, plans simulated including the effects of random and systematic errors deviate substantially from the nominal plan. The use of PTVs for dose evaluation in the nominal plan improves agreement with evaluated GTV, CTV, and nodal dose values under simulated setup errors. PTV concepts should be used for SIB-IMRT head-and-neck squamous cell carcinoma patients, although the size of the margins may be less than those used with three-dimensional conformal radiation therapy.     

Dosimetric consequences of the application of a rectum hull-planning volume for treatment planning of intensity modulated radiotherapy of prostate cancer

The present study evaluated a hull-volume definition strategy for the planning organ at risk volume (PRV) for the rectum in the planning of radiotherapy of prostate cancer. The bounding volumes of rectum contours of 1 to 5 CT scans were compared on the basis of the rectum coverage probabilities for 5 patients. In addition, IMRT treatment plans were optimized using the rectum hull PRV5 of 5 CTs and each of the conventional rectum contours PRV1. The plans were compared on the basis of the organ doses caused by the individual organ motion. PRV5 allowed to cover the rectum with a probability of nearly 90% (PRV1 67%). Rectal wall dose showed a great variability for PRV1, while planned and treatment dose agreed well for PRV5 due to the improved geometric information which resulted in a better rectal sparing. In conclusion, the rectum hull-volume PRV5 is a well suited PRV for planning of IMRT dose distributions allowing dose escalation as well as rectal sparing.     

Is uniform target dose possible in IMRT plans in the head and neck?

: Various published reports involving intensity-modulated radiotherapy (IMRT) plans developed using automated optimization (inverse planning) have demonstrated highly conformal plans. These reported conformal IMRT plans involve significant target dose inhomogeneity, including both overdosage and underdosage within the target volume. In this study, we demonstrate the development of optimized beamlet IMRT plans that satisfy rigorous dose homogeneity requirements for all target volumes (e.g., ±5%), while also sparing the parotids and other normal structures.

: The treatment plans of 15 patients with oropharyngeal cancer who were previously treated with forward-planned multisegmental IMRT were planned again using an automated optimization system developed in-house. The optimization system allows for variable sized beamlets computed using a three-dimensional convolution/superposition dose calculation and flexible cost functions derived from combinations of clinically relevant factors (costlets) that can include dose, dose-volume, and biologic model-based costlets. The current study compared optimized IMRT plans designed to treat the various planning target volumes to doses of 66, 60, and 54 Gy with varying target dose homogeneity while using a flexible optimization cost function to minimize the dose to the parotids, spinal cord, oral cavity, brainstem, submandibular nodes, and other structures.

: In all cases, target dose uniformity was achieved through steeply varying dose-based costs. Differences in clinical plan evaluation metrics were evaluated for individual cases (eight different target homogeneity costlets), and for the entire cohort of plans. Highly conformal plans were achieved, with significant sparing of both the contralateral and ipsilateral parotid glands. As the homogeneity of the target dose distributions was allowed to decrease, increased sparing of the parotids (and other normal tissues) may be achieved. However, it was shown that relatively few patients would benefit from the use of increased target inhomogeneity, because the range of improvement in the parotid dose is relatively limited. Hot spots in the target volumes are shown to be unnecessary and do not assist in normal tissue sparing.

: Sparing of both parotids in patients receiving bilateral neck radiation can be achieved without compromising strict target dose homogeneity criteria. The geometry of the normal tissue and target anatomy are shown to be the major factor necessary to predict the parotid sparing that will be possible for any particular case.     

Segmental IMRT for oropharyngeal cancer in a clinical setting.

BACKGROUND AND PURPOSE: To develop a segmental intensity-modulated radiotherapy (IMRT) technique for the treatment of oropharyngeal cancer. PATIENTS AND METHODS: Eight patients previously treated for oropharyngeal cancer were replanned with segmental IMRT. The dose distribution was optimized using beam geometries consisting of 3, 5, 7 and 9 equiangular beams. The optimization procedure resulted in a theoretical fluence for each beam. In order to vary the number of segments, the optimized fluence was divided into four different equidistant levels. The final dose distribution was calculated using clinically deliverable segments obtained from optimized fluence. RESULTS: For our segmental IMRT technique the dose homogeneity within the target volumes improved when the total number of segments increased and reached a saturation level at approximately 150 segments. Seven beams were sufficient to achieve the saturation level for dose homogeneity. The mean dose to the parotid glands depended on the beam geometry and tumor location and did not depend on the number of segments. On average the mean dose to the contralateral parotid gland was 35.7 Gy (27.1-39.9 Gy) for all seven beam plans. CONCLUSIONS: Seven beams are sufficient to achieve an acceptable dose homogeneity within the target volumes and significant parotid sparing. These results will be used to introduce IMRT in routine clinical practice.     

Parotid Gland Dose in Intensity-Modulated Radiotherapy for Head and Neck Cancer: Is What You Plan What You Get?

PURPOSE: To quantify the differences between planned and delivered parotid gland and target doses, and to assess the benefits of daily bone alignment for head and neck cancer patients treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Eleven head and neck cancer patients received two CT scans per week with an in-room CT scanner over the course of their radiotherapy. The clinical IMRT plans, designed with 3-mm to 4-mm planning margins, were recalculated on the repeat CT images. The plans were aligned using the actual treatment isocenter marked with radiopaque markers (BB) and bone alignment to the cervical vertebrae to simulate image-guided setup. In-house deformable image registration software was used to map daily dose distributions to the original treatment plan and to calculate a cumulative delivered dose distribution for each patient. RESULTS: Using conventional BB alignment led to increases in the parotid gland mean dose above the planned dose by 5 to 7 Gy in 45% of the patients (median, 3.0 Gy ipsilateral, p = 0.026; median, 1.0 Gy contralateral, p = 0.016). Use of bone alignment led to reductions relative to BB alignment in 91% of patients (median, 2 Gy; range, 0.3-8.3 Gy; 15 of 22 parotids improved). However, the parotid dose from bone alignment was still greater than planned (median, 1.0 Gy, p = 0.007). Neither approach affected tumor dose coverage. CONCLUSIONS: With conventional BB alignment, the parotid gland mean dose was significantly increased above the planned mean dose. Using daily bone alignment reduced the parotid dose compared with BB alignment in almost all patients. A 3- to 4-mm planning margin was adequate for tumor dose coverage.     

Intensity-modulated radiotherapy in nasopharyngeal carcinoma: dosimetric advantage over conventional plans and feasibility of dose escalation

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) with two-dimensional RT (2D-RT) and three-dimensional conformal radiotherapy (3D-CRT) treatment plans in different stages of nasopharyngeal carcinoma and to explore the feasibility of dose escalation in locally advanced disease. MATERIALS AND METHODS: Three patients with different stages (T1N0M0, T2bN2M0 with retrostyloid extension, and T4N2M0) were selected, and 2D-RT, 3D-CRT, and IMRT treatment plans (66 Gy) were made for each of them and compared with respect to target coverage, normal tissue sparing, and tumor control probability/normal tissue complication probability values. In the Stage T2b and T4 patients, the IMRT 66-Gy plan was combined with a 3D-CRT 14-Gy boost plan using a 3-mm micromultileaf collimator, and the dose-volume histograms of the summed plans were compared with their corresponding 66-Gy 2D-RT plans. RESULTS: In the dosimetric comparison of 2D-RT, 3D-CRT, and IMRT treatment plans, the T1N0M0 patient had better sparing of the parotid glands and temporomandibular joints with IMRT (dose to 50% parotid volume, 57 Gy, 50 Gy, and 31 Gy, respectively). In the T2bN2M0 patient, the dose to 95% volume of the planning target volume improved from 57.5 Gy in 2D-RT to 64.8 Gy in 3D-CRT and 68 Gy in IMRT. In the T4N2M0 patient, improvement in both target coverage and brainstem/temporal lobe sparing was seen with IMRT planning. In the dose-escalation study for locally advanced disease, IMRT 66 Gy plus 14 Gy 3D-CRT boost achieved an improvement in the therapeutic ratio by delivering a higher dose to the target while keeping the normal organs below the maximal tolerance dose. CONCLUSIONS: IMRT is useful in treating all stages of nonmetastatic nasopharyngeal carcinoma because of its dosimetric advantages. In early-stage disease, it provides better parotid gland sparing. In locally advanced disease, IMRT offers better tumor coverage and normal organ sparing and allows room for dose escalation.     

Dosimetric predictors of xerostomia for head-and-neck cancer patients treated with the smart (simultaneous modulated accelerated radiation therapy) boost technique

PURPOSE: To evaluate the predictors of xerostomia in the treatment of head-and-neck cancers treated with intensity-modulated radiation therapy (IMRT), using the simultaneous modulated accelerated radiation therapy (SMART) boost technique. Dosimetric parameters of the parotid glands are correlated to subjective salivary gland function. MATERIALS AND METHODS: Between January 1996 and June 2000, 30 patients with at least 6 months follow-up were evaluated for subjective xerostomia after being treated definitively for head-and-neck cancer with the SMART boost technique. Threshold limits for the ipsilateral and contralateral parotid glands were 35 Gy and 25 Gy, respectively. Dosimetric parameters to the parotid glands were evaluated. The median follow-up time was 38.5 months (mean 39.9 months). The results of the dosimetric parameters and questionnaire were statistically correlated. RESULTS: Xerostomia was assessed with a 10-question subjective salivary gland function questionnaire. The salivary gland function questionnaire (questions 1, 2, 3, 4, 6, and 9) correlated significantly with the dosimetric parameters (mean and maximum doses and volume and percent above tolerance) of the parotid glands. These questions related to overall comfort, eating, and abnormal taste. Questions related to thirst, difficulty with speech or sleep, and the need to carry water daily did not correlate statistically with the dosimetric parameters of the parotid glands. CONCLUSIONS: Questions regarding overall comfort, eating, and abnormal taste correlated significantly with the dosimetric parameters of the parotid glands. Questions related to thirst, difficulty with speech or sleep, and the need to carry water daily did not correlate statistically with the dosimetric parameters of the parotid glands. Dosimetric sparing of the parotid glands improved subjective xerostomia. IMRT in the treatment of head-and-neck cancer can be exploited to preserve the parotid glands and decrease xerostomia. This is feasible even with an accelerated treatment regimen like the SMART boost. More patients need to be evaluated using IMRT to identify relevant dosimetric parameters.     

Optimisation of radiotherapy for carcinoma of the parotid gland: a comparison of conventional, three-dimensional conformal, and intensity-modulated techniques.

BACKGROUND AND PURPOSE: To compare external beam radiotherapy techniques for parotid gland tumours using conventional radiotherapy (RT), three-dimensional conformal radiotherapy (3DCRT), and intensity-modulated radiotherapy (IMRT). To optimise the IMRT techniques, and to produce an IMRT class solution. MATERIALS AND METHODS: The planning target volume (PTV), contra-lateral parotid gland, oral cavity, brain-stem, brain and cochlea were outlined on CT planning scans of six patients with parotid gland tumours. Optimised conventional RT and 3DCRT plans were created and compared with inverse-planned IMRT dose distributions using dose-volume histograms. The aim was to reduce the radiation dose to organs at risk and improve the PTV dose distribution. A beam-direction optimisation algorithm was used to improve the dose distribution of the IMRT plans, and a class solution for parotid gland IMRT was investigated. RESULTS: 3DCRT plans produced an equivalent PTV irradiation and reduced the dose to the cochlea, oral cavity, brain, and other normal tissues compared with conventional RT. IMRT further reduced the radiation dose to the cochlea and oral cavity compared with 3DCRT. For nine- and seven-field IMRT techniques, there was an increase in low-dose radiation to non-target tissue and the contra-lateral parotid gland. IMRT plans produced using three to five optimised intensity-modulated beam directions maintained the advantages of the more complex IMRT plans, and reduced the contra-lateral parotid gland dose to acceptable levels. Three- and four-field non-coplanar beam arrangements increased the volume of brain irradiated, and increased PTV dose inhomogeneity. A four-field class solution consisting of paired ipsilateral coplanar anterior and posterior oblique beams (15, 45, 145 and 170 degrees from the anterior plane) was developed which maintained the benefits without the complexity of individual patient optimisation. CONCLUSIONS: For patients with parotid gland tumours, reduction in the radiation dose to critical normal tissues was demonstrated with 3DCRT compared with conventional RT. IMRT produced a further reduction in the dose to the cochlea and oral cavity. With nine and seven fields, the dose to the contra-lateral parotid gland was increased, but this was avoided by optimisation of the beam directions. The benefits of IMRT were maintained with three or four fields when the beam angles were optimised, but were also achieved using a four-field class solution. Clinical trials are required to confirm the clinical benefits of these improved dose distributions.     

Comparison of treatment plans using intensity-modulated radiotherapy and three-dimensional conformal radiotherapy for paranasal sinus carcinoma

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) treatment planning with three-dimensional conformal radiotherapy (3D-CRT) planning for paranasal sinus carcinoma. MATERIALS AND METHODS: Treatment plans using traditional 3-field technique, 3D-CRT planning, and inverse planning IMRT were developed for a case of paranasal sinus cancer requiring adjuvant radiotherapy. Plans were compared with respect to dose conformality, dose-volume histograms, doses to critical normal tissues, and ease of treatment delivery. RESULTS: The inverse-planned IMRT technique was more conformal around the tumor target volume than conventional techniques. The dose-volume histograms demonstrated significantly better critical normal-tissue sparing with the IMRT plans, while able to deliver a minimum dose of 60 Gy to the clinical tumor volume and 70 Gy to the gross tumor volume. Acute toxicities in our analysis were minimal. CONCLUSIONS: IMRT planning provided improved tumor target coverage when compared to 3D-CRT treatment planning. There was significant sparing of optic structures and other normal tissues, including the brainstem. Inverse planning IMRT provided the best treatment for all paranasal sinus carcinomas, but required stringent immobilization criteria. Further studies are needed to establish the true clinical advantage of this modality.     

鼻咽癌调强放疗后近期腮腺功能影响因素分析

[目的]总结鼻咽癌调强放疗后腮腺功能影响因素。[方法]收集2008年7月至2009年8月初治的20例鼻咽癌调强放疗靶区及腮腺剂量学参数,随访其放疗后3个月口干情况,分析腮腺受照剂量与口干分级之间的关系。[结果]20例接受调强放疗鼻咽癌腮腺平均剂量41.25Gy,患侧腮腺V20：96.77%,V30：80.56%,V40：52.43%,健侧腮腺V20：971.47%,V30：69.95%,V40：40.85%。放疗后3个月轻度、中度、重度口干发生率分别为15%、55%、30%,口干分级与腮腺平均剂量、患侧及健侧腮腺V20、V30、V40呈正相关。[结论]鼻咽癌调强放疗后腮腺功能与腮腺受照体积、剂量显著相关。     

腮腺分区勾画对伴有双侧颈部Ⅱ区淋巴结转移鼻咽癌调强放射治疗计划优化的影响

[目的]探讨腮腺分区勾画对伴有双颈部Ⅱ区淋巴结转移鼻咽癌调强放射治疗计划优化的影响。[方法]选择接受调强放疗的双颈部Ⅱ区淋巴结转移的鼻咽癌患者20例,利用Corvus6．3调强治疗计划系统设计3种治疗计划：既未进行腮腺分区勾画的常规计划（Pian01：将腮腺沿下颌后静脉前外缘作与腮腺后界的平行线,将腮腺分成前外与后内两部分,分别予剂量限制,重新计划优化,得到将腮腺分区勾画的计划（Planl）;将腮腺分区勾画的CT序列定义为模体,由常规计划（Plan0）进行正向运算得到计划2（Plan2）。比较Planl与Plan2在靶区和正常组织的剂量分布。『结果]两套计划均符合RTOG0615靶区及正常组织剂量限制要求。采用该腮腺分区勾画方法能够降低整个腺体的平均辐射剂量、V15以及〈20Gy体积,这主要归功于降低了腮腺前外侧区约20％的平均辐射剂量、30％～40％的V。[结论]在伴有双颈部Ⅱ区淋巴结转移鼻咽癌IMRT中,腮腺分区勾画在理论上和剂量学上具有可行性,尤其降低了干细胞集中部位（腮腺前外侧区）的辐射剂量．具有一定推广应用价值,对腮腺分泌功能的影响有待前瞻性随机试验证实。     

A prospective study of salivary function sparing in patients with head-and-neck cancers receiving intensity-modulated or three-dimensional radiation therapy: initial results

OBJECTIVES: In a prospective clinical study, we tested the hypothesis that sparing the parotid glands may result in significant objective and subjective improvement of xerostomia in patients with head-and-neck cancers. The functional outcome 6 months after the completion of radiation therapy is presented. METHODS AND MATERIALS: From February 1997 to February 1999, 41 patients with head-and-neck cancers were enrolled in a prospective salivary function study. Inverse-planning intensity-modulated radiation therapy (IMRT) was used to treat 27 patients, and forward-planning three-dimensional radiation therapy in 14. To avoid potential bias in data interpretation, only patients whose submandibular glands received greater than 50 Gy were eligible. Attempts were made to spare the superficial lobe of the parotid glands to avoid underdosing tumor targets in the parapharyngeal space; however, the entire parotid volume was used to compute dose-volume histograms (DVHs) for this analysis. DVHs were computed for each gland separately. Parotid function was assessed objectively by measuring stimulated and unstimulated saliva flow before and 6 months after the completion of radiation therapy. Measurements were converted to flow rate (mL/min) and normalized relative to that before treatment. The corresponding quality-of-life (QOL) outcome was assessed by five questions regarding the patient's oral discomfort and eating/speaking problems. RESULTS: We observed a correlation between parotid mean dose and the fractional reduction of stimulated saliva output at 6 months after the completion of radiation therapy. We further examined whether the functional outcome could be modeled as a function of dose. Two models were found to describe the dose-response data well. The first model assumed that each parotid gland is comprised of multiple independent parallel functional subunits (corresponding to computed tomography voxels) and that each gland contributes equally to overall flow, and that saliva output decreases exponentially as a quadratic function of irradiation dose to each voxel. The second approach uses the equivalent uniform dose (EUD) metrics, which assumes loss of salivary function with increase in EUD for each parotid gland independently. The analysis suggested that the mean dose to each parotid gland is a reasonable indicator for the functional outcome of each gland. The corresponding exponential coefficient was 0.0428/Gy (95% confidence interval: 0.01, 0.09). The QOL questions on eating/speaking function were significantly correlated with stimulated and unstimulated saliva flow at 6 months. In a multivariate analysis, a toxicity score derived from the model based on radiation dose to the parotid gland was found to be the sole significant predictive factor for xerostomia. Neither radiation technique (IMRT vs. non-IMRT) nor chemotherapy (yes or no) independently influenced the functional outcome of the salivary glands. CONCLUSION: Sparing of the parotid glands translates into objective and subjective improvement of both xerostomia and QOL scores in patients with head-and-neck cancers receiving radiation therapy. Modeling results suggest an exponential relationship between saliva flow reduction and mean parotid dose for each gland. We found that the stimulated saliva flow at 6 months after treatment is reduced exponentially, for each gland independently, at a rate of approximately 4% per Gy of mean parotid dose.     

Target volume definition for head and neck intensity modulated radiotherapy: pre-clinical evaluation of PARSPORT trial guidelines

AimsThere is considerable controversy surrounding target volume definition for parotid-sparing intensity modulated radiotherapy (IMRT) for head and neck cancer. The aim of this study was to evaluate the dosimetric and radiobiological predictors of outcome anticipated by application of the detailed target volume definition guidelines agreed for the UK multicentre randomised controlled trial of parotid-sparing IMRT (PARSPORT).Materials and methodsFive patients eligible for the study were delineated using the trial guidelines. Following the protocol, plans were produced to treat these volumes with three-dimensional radiotherapy (control arm) and IMRT aimed to spare dose to the contralateral parotid gland (experimental arm). Dosimetric comparisons were made between plans, and normal tissue complication probability (NTCP) modelling for salivary glands was carried out.ResultsDoses delivered to the planning target volumes (PTV) were similar with each technique, although IMRT produced more homogeneous irradiation of the PTV. Mean doses to the contralateral parotid gland were 22.4 ± 1.7 Gy with the IMRT plans vs 60.0 ± 7.2 Gy with three-dimensional radiotherapy, P = 0.0003. Calculated contralateral parotid gland NTCP values for grade 2 xerostomia were 20–22% for IMRT and 98–100% for three-dimensional radiotherapy (P < 0.0001).ConclusionPre-clinical evaluation of the PARSPORT trial target volume definition guidelines provides theoretical support for a significant reduction in xerostomia rates. These data await confirmation from the clinical trial results.     

Advantage of protons compared to conventional X-ray or IMRT in the treatment of a pediatric patient with medulloblastoma

PURPOSE: To compare treatment plans from standard photon therapy to intensity modulated X-rays (IMRT) and protons for craniospinal axis irradiation and posterior fossa boost in a patient with medulloblastoma. METHODS: Proton planning was accomplished using an in-house 3D planning system. IMRT plans were developed using the KonRad treatment planning system with 6-MV photons. RESULTS: Substantial normal-tissue dose sparing was realized with IMRT and proton treatment of the posterior fossa and spinal column. For example, the dose to 90% of the cochlea was reduced from 101.2% of the prescribed posterior fossa boost dose from conventional X-rays to 33.4% and 2.4% from IMRT and protons, respectively. Dose to 50% of the heart volume was reduced from 72.2% for conventional X-rays to 29.5% for IMRT and 0.5% for protons. Long-term toxicity with emphasis on hearing and endocrine and cardiac function should be substantially improved secondary to nontarget tissue sparing achieved with protons. CONCLUSION: The present study clearly demonstrates the advantage of conformal radiation methods for the treatment of posterior fossa and spinal column in children with medulloblastoma, when compared to conventional X-rays. Of the two conformal treatment methods evaluated, protons were found to be superior to IMRT.     

Level II lymph nodes and radiation-induced xerostomia

PURPOSE: To investigate the influence of the cranial border of electively irradiated Level II lymph nodes on xerostomia in patients with oropharyngeal cancer using three-dimensional conformal and intensity-modulated radiotherapy (3D-CRT and IMRT). METHODS AND MATERIALS: The target volumes and organs at risk were delineated on the planning CT scans of 12 patients. Two elective target volumes were delineated. The first had the transverse process of the C1 atlas and the second had the transverse process of the C2 axis as cranial border of the Level II lymph nodes. 3D-CRT and IMRT planning were performed for both elective volumes, resulting in two plans per patient and technique, called the C1 and C2 plans, respectively. Irradiation of the ipsilateral elective volume up to C1 and the contralateral up to C2 was also performed for IMRT. The normal tissue complication probability (NTCP) for xerostomia 1 year after RT was calculated using the parotid mean dose. RESULTS: The average mean dose +/- standard deviation (SD) to the contralateral parotid gland was reduced from 33 +/- 5 Gy for the IMRT C1 plans to 26 +/- 4 Gy for the IMRT C2 plans and from 51 +/- 6 Gy to 49 +/- 7 Gy for the 3D-CRT C1 and C2 plans, respectively. The associated NTCP +/- SD for xerostomia was 38% +/- 10% for IMRT C1 plans and 24% +/- 6% for IMRT up to C2 on the contralateral side, regardless of which cranial border was irradiated on the ipsilateral side. For the 3D-CRT C1 and C2 plans, an NTCP value of 74% +/- 12% and 71% +/- 15% was obtained, respectively. The NTCP for xerostomia of the ipsilateral parotid gland was 53% +/- 17% and 45% +/- 20% for the IMRT C1 and C2 plans and 89% +/- 11% and 87% +/- 12% for the 3D-CRT C1 and C2 plans, respectively. CONCLUSION: Lowering the cranial border of the Level II lymph nodes from C1 to C2, in the case of bilateral elective neck irradiation, could be considered on the contralateral side when the risk of metastasis on that side is very low. This is especially true when IMRT is used, because the relative reduction of NTCP for xerostomia 1 year after RT could be up to 68% compared with conventional conformal RT up to C1.