Lon H. Marsh

Parotid gland sparing in patients undergoing bilateral head and neck irradiation: Techniques and early results.

PURPOSE To minimize xerostomia in patients receiving bilateral head and neck irradiation (RT) by using conformal RT planning to spare a significant volume of one parotid gland from radiation. METHODS AND MATERIALS The study involved 15 patients with head and neck tumors in whom bilateral neck radiation was indicated. The major salivary glands and the targets (tumor, surgical bed, metastases to lymph nodes, and the locations of lymph nodes at risk for metastases) were outlined on axial computed tomography images. Beams-eye view (BEV) displays were used to construct conformal beams that delivered the prescribed doses to the targets while sparing from direct radiation most of one parotid gland. The gland that was planned to be spared resided in the neck side that was judged in each patient to be at a lesser risk of metastatic disease. Major salivary gland flow rates and the responses to a subjective xerostomia questionnaire were assessed before, during, and after radiation. RESULTS Radiation planning for patients with central oropharyngeal tumors required the generation of multiple axial nonopposed beams. The resulting isodoses encompassed the targets, including the retropharyngeal nodes and the jugular nodes up to the base of skull bilaterally, while limiting the dose to the oral cavity, spinal cord, and one parotid gland. For patients with lateralized tumors, the ipsilateral neck side was treated up to the base of the skull; in the contralateral neck side, the treatment included the subdigastric nodes but excluded the jugular nodes at the base of the skull and most of the parotid gland. This was accomplished by a moderate gantry angle that was chosen using the BEV displays. Three months following the completion of radiation, the spared parotid glands retained on average 50% of their unstimulated and stimulated flows. In contrast, no saliva flow was measured from the unspared glands in any of the patients. Subjective xerostomia was absent, mild, or not different from that reported before radiation in 10 of 15 patients (67%). CONCLUSION Partial parotid gland sparing is feasible by using three-dimensional planning in patients undergoing bilateral head and neck radiation. Approximately 50% of the saliva flow from the spared glands may be retained, and most patients thus treated have no or mild xerostomia in the early period after the completion of radiation. Whether tumor control and late complications are comparable to standard radiation will be assessed as more experience is gained.

Comprehensive irradiation of head and neck cancer using conformal multisegmental fields: Assessment of target coverage and noninvolved tissue sparing

PURPOSE Conformal treatment using static multisegmental intensity modulation was developed for patients requiring comprehensive irradiation for head and neck cancer. The major aim is sparing major salivary gland function while adequately treating the targets. To assess the adequacy of the conformal plans regarding target coverage and dose homogeneity, they were compared with standard irradiation plans. METHODS AND MATERIALS Fifteen patients with stage III/IV head and neck cancer requiring comprehensive, bilateral neck irradiation participated in this study. CT-based treatment plans included five to six nonopposed fields, each having two to four in-field segments. Fields and segments were devised using beams eye views of the planning target volumes (PTVs), noninvolved organs, and isodose surfaces, to achieve homogeneous dose distribution that encompassed the targets and spared major salivary gland tissue. For comparison, standard three-field radiation plans were devised retrospectively for each patient, with the same CT-derived targets used for the clinical (conformal) plans. Saliva flow rates from each major salivary gland were measured before and periodically after treatment. RESULTS On average, the minimal dose to the primary PTVs in the conformal plans [95.2% of the prescribed dose, standard deviation (SD) 4%] was higher than in the standard plans (91%, SD 7%; p = 0.02), and target volumes receiving <95% or <90% of the prescribed dose were smaller in the conformal plans (p = 0.004 and 0.02, respectively). Similar advantages of the conformal plans compared to standard plans were found in ipsilateral jugular nodes PTV coverage. The reason for underdosing in the standard treatment plans was primarily failure of electron beams to fully encompass targets. No significant differences were found in contralateral jugular or posterior neck nodes coverage. The minimal dose to the retropharyngeal nodes was higher in the standard plans. However, all conformal plans achieved the planning goal of delivering 50 Gy to these nodes. In the conformal plans, the magnitude and volumes of high doses in noninvolved tissue were significantly reduced. The main reasons for hot spots in the standard plans (whose dose calculations included missing tissue compensators) were photon/electron match line inhomogeneities, which were avoided in the conformal plans. The mean doses to all the major salivary glands, notably the contralateral parotid (receiving on average 32% of the prescribed dose, SD 7%) were significantly lower in the conformal plans compared with standard radiation plans. The mean dose to the noninvolved oral cavity tended to be lower in the conformal plans (p = 0.07). One to 3 months after radiation, on average 60% (SD 49%) of the preradiation saliva flow rate was retained in the contralateral parotid glands and 10% (SD 16%) was retained in the submandibular/sublingual glands. CONCLUSIONS Planning and delivery of comprehensive irradiation for head and neck cancer using static, multisegmental intensity modulation are feasible. Target coverage has not been compromised and dose distributions in noninvolved tissue are favorable compared with standard radiation. Substantial major salivary gland function can be retained.

Salivary Gland Sparing and Improved Target Irradiation by Conformal and Intensity Modulated Irradiation of Head and Neck Cancer

The goals of this study were to facilitate sparing of the major salivary glands while adequately treating tumor targets in patients requiring comprehensive bilateral neck irradiation (RT), and to assess the potential for improved xerostomia. Since 1994 techniques of target irradiation and locoregional tumor control with conformal and intensity modulated radiation therapy (IMRT) have been developed. In patients treated with these modalities, the salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands’ dose volume histograms (DVHs). In addition, subjective xerostomia questionnaires have been developed and validated. The pattern of locoregional recurrence has been examined from computed tomography (CT) scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans, and regenerating the dose distributions at the recurrence sites. Treatment plans for target coverage and dose homogeneity using static, multisegmental IMRT were found to be significantly better than standard RT plans. In addition, significant parotid gland sparing was achieved in the conformal plans. The relationships among dose, irradiated volume, and the residual saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean radiation dose of 26 Gy was found to be the threshold for preserved stimulated saliva flow. Xerostomia questionnaire scores suggested that xerostomia was significantly reduced in patients irradiated with bilateral neck, parotid-sparing RT, compared to patients with similar tumors treated with standard RT. Examination of locoregional tumor recurrence patterns revealed that the large majority of recurrences occurred inside targets, in areas that had been judged to be at high risk and that had received RT doses according to the perceived risk. Tangible gains in salivary gland sparing and target coverage are being achieved, and an improvement in some measures of quality of life is suggested by our findings. Additional reduction of xerostomia may be achieved by further sparing of the salivary glands and the non-involved oral cavity. A mean parotid gland dose of ≤ 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to areas judged to be at highest risk may improve tumor control.

CONSIDERATION OF DOSE LIMITS FOR ORGANS AT RISK OF THORACIC RADIOTHERAPY: ATLAS FOR LUNG, PROXIMAL BRONCHIAL TREE, ESOPHAGUS, SPINAL CORD, RIBS, AND BRACHIAL PLEXUS

PURPOSE To review the dose limits and standardize the three-dimenional (3D) radiographic definition for the organs at risk (OARs) for thoracic radiotherapy (RT), including the lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. METHODS AND MATERIALS The present study was performed by representatives from the Radiation Therapy Oncology Group, European Organization for Research and Treatment of Cancer, and Soutwestern Oncology Group lung cancer committees. The dosimetric constraints of major multicenter trials of 3D-conformal RT and stereotactic body RT were reviewed and the challenges of 3D delineation of these OARs described. Using knowledge of the human anatomy and 3D radiographic correlation, draft atlases were generated by a radiation oncologist, medical physicist, dosimetrist, and radiologist from the United States and reviewed by a radiation oncologist and medical physicist from Europe. The atlases were then critically reviewed, discussed, and edited by another 10 radiation oncologists. RESULTS Three-dimensional descriptions of the lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus are presented. Two computed tomography atlases were developed: one for the middle and lower thoracic OARs (except for the heart) and one focusing on the brachial plexus for a patient positioned supine with their arms up for thoracic RT. The dosimetric limits of the key OARs are discussed. CONCLUSIONS We believe these atlases will allow us to define OARs with less variation and generate dosimetric data in a more consistent manner. This could help us study the effect of radiation on these OARs and guide high-quality clinical trials and individualized practice in 3D-conformal RT and stereotactic body RT.

Dose-volume complication analysis for visual pathway structures of patients with advanced paranasal sinus tumors

PURPOSE The purpose of the present work was to relate dose and volume information to complication data for visual pathway structures in patients with advanced paranasal sinus tumors. METHODS AND MATERIALS Three-dimensional (3D) dose distributions for chiasm, optic nerve, and retina were calculated and analyzed for 20 patients with advanced paranasal sinus malignant tumors. 3D treatment planning with beams eye view capability was used to design beam and block arrangements, striving to spare the contralateral orbit (to lessen the chance of unilateral blindness) and frequently the ipsilateral orbit (to help prevent bilateral blindness). Point doses, dose-volume histogram analysis, and normal tissue complication probability (NTCP) calculations were performed. Published tolerance doses that indicate significant risk of complications were used as guidelines for analysis of the 3D dose distributions. RESULTS Point doses, percent volume exceeding a specified published tolerance dose, and NTCP calculations are given in detail for patients with complications versus patients without complications. Two optic nerves receiving maximum doses below the published tolerance dose sustained damage (mild vision loss). Three patients (of 13) without optic nerve sparing and/or chiasm sparing had moderate or severe vision loss. Complication data, including individual patient analysis to estimate overall risk for loss of vision, are given. CONCLUSION 3D treatment planning techniques were used successfully to provide bilateral sparing of the globe for most patients. It was more difficult to spare the optic nerves, especially on the ipsilateral side, when prescription dose exceeded the normal tissue tolerance doses. NTCP calculations may be useful in assessing complication risk better than point dose tolerance criteria for the chiasm, optic nerve, and retina. It is important to assess the overall risk of blindness for the patient in addition to the risk for individual visual pathway structures.

Optimization and clinical use of multisegment intensity-modulated radiation therapy for high-dose conformal therapy

Intensity-modulated radiation therapy (IMRT) may be performed with many different treatment delivery techniques. This article summarizes the clinical use and optimization of multisegment IMRT plans that have been used to treat more than 350 patients with IMRT over the last 4.5 years. More than 475 separate clinical IMRT plans are reviewed, including treatments of brain, head and neck, thorax, breast and chest wall, abdomen, pelvis, prostate, and other sites. Clinical planning, plan optimization, and treatment delivery are summarized, including efforts to minimize the number of additional intensity-modulated segments needed for particular planning protocols. Interactive and automated optimization of segmental and full IMRT approaches are illustrated, and automation of the segmental IMRT planning process is discussed.

Potential benefits of eliminating planning target volume expansions for patient breathing in the treatment of liver tumors

PURPOSE To investigate potential benefits derived from reduction or elimination of planning target volume (PTV) margins associated with patient breathing through examination of hepatic tumors treated with conformal therapy. METHODS AND MATERIALS We reviewed the treatment plans of 50 patients who had previously received conformal partial organ liver irradiation for treatment of hepatic malignancies. PTVs for these plans included expansions (1-2 cm) for patient breathing. Data consisted of the three-dimensional dose distributions computed for the conformal plans generated for these volumes, and also for plans using identical beam arrangements but smaller block margins to treat planning target volumes that did not include the expansions for breathing. We calculated effective volumes (V(eff)) and normal tissue complication probabilities (NTCP) using dose-volume histograms for normal liver and analyzed changes in: V(eff), NTCP at the prescription dose, doses associated with selected NTCP levels, and tumor control probabilities (TCP) at these new dose levels. RESULTS Elimination of the patient breathing components of the PTVs for these conformal treatments of liver tumors: (a) decreased the average V(eff) by 5%; (b) decreased the average predicted NTCP at the prescription (isocenter) dose used to treat the patients by 4.5%; (c) increased the average target volume (isocenter) dose associated with low (1-10%) predicted normal liver NTCP by 6-8 Gy, which corresponded to (d) a predicted average 6-7% increase in TCP for aggressive liver tumors. Plans with PTV expansions for breathing that occurred mostly within the liver showed greatest potential benefit. CONCLUSIONS Elimination of the margin added to hepatic target volumes for patient ventilation could lead to clinically meaningful increases in dose without increasing the predicted frequency of complications.

A fluence convolution method to account for respiratory motion in three-dimensional dose calculations of the liver: A Monte Carlo study

We describe the implementation of a fluence convolution method to account for the influence of superior-inferior (SI) respiratory induced motion on a Monte Carlo-based dose calculation of a tumor located in the liver. This method involves convolving the static fluence map with a function describing the SI motion of the liver-the motion function has been previously derived from measurements of diaphragm movement observed under fluoroscopy. Significant differences are noted between fluence-convolved and static dose distributions in an example clinical treatment plan; hot and cold spots (on the order of 25%) are observed in the fluence-convolved plan at the superior and inferior borders of the liver, respectively. This study illustrates that the fluence convolution method can be incorporated into Monte Carlo dose calculation algorithms to account for some of the effects of patient breathing during radiotherapy treatment planning, thus leading to more accurate dose calculations.

Customized Gynecologic Interstitial Implants: CT-Based Planning, Dose Evaluation, and Optimization Aided by Laparotomy

PURPOSE Interstitial perineal implants may be utilized to deliver a high local radiation dose in the treatment of advanced gynecologic malignancies. Lack of knowledge of the precise anatomic relationships between the implant and the target and critical organs may limit efficacy and increase complication risks. Computed tomography (CT)-based planning, dose evaluation, and optimization of customized interstitial implants, aided by laparotomy, have been developed to overcome these limitations. METHODS AND MATERIALS Twenty patients with locally advanced gynecologic malignancies treated between May 1990 to October 1996 with external irradiation and one or two implants. Interstitial implants were performed when intracavitary brachytherapy was judged to be inadequate or when the response to external radiation and an intracavitary implant was not satisfactory. Customized interstitial implants were planned using preimplantation CT to determine catheter angles and paths that best implanted the target while avoiding pelvic bones and organs. Laparotomy aimed at lysing bowel adhesions, placement of omental carpet, and refining needle placement. Postimplantation CT was used for loading optimization and dose evaluation. RESULTS Catheter angles 15-25 degrees were found to adequately implant anteriorly laying targets while avoiding pubic bones and bladder. Adhesiolysis of bowel loops from the vaginal apex was required in patients with prior hysterectomy. Small modifications in catheter placements were made during laparotomy in all implants. Postimplantation CTs showed deviations of the catheter positions compared with the planning CTs and were essential in determining target and organ doses and loading optimization. At a median follow-up of 42 months (range: 9-80 months), local control rate is 55% and disease-free survival 40%. Late complications occurred in 2 of 11 of patients without local recurrence. CONCLUSIONS CT-based planning, loading optimization, and dose evaluation of customized implants improve radiation dose delivery. Laparotomy enhances implant accuracy and safety. Local tumor control rate is still unsatisfactory. It reflects the shortcomings of technical advances alone in poor prognosis tumors like those selected for this series.

Preservation of parotid function after external beam irradiation in head and neck cancer patients: A feasibility study using 3-dimensional treatment planning

PURPOSE Radiation-induced xerostomia is a frequent complication and major cause of morbidity in head and neck cancer patients. The severity of xerostomia is related to radiation dose and the amount of parotid tissue included in the irradiated volume. To reduce this side-effect and preserve salivary function, we have evaluated the use of 3-dimensional (3-D) treatment planning to spare the contralateral parotid gland in twelve patients undergoing radiation therapy for head and neck cancers. METHODS AND MATERIALS In each case, beams eye view displays were used to design beam and blocking arrangements that excluded the contralateral parotid. Ten patients were treated with 2 nonopposing oblique fields in the axial and non-axial plane while two patients required a non-axial, non-coplanar 3-field arrangement. These 3-D treatment plans were also compared with conventional 2-dimensional (2-D) plans. The 2-dimensional plans were designed independently of the 3-D treatment planning information using the orthogonal radiographs and hard copies of the computed tomography scans. RESULTS An average of 1.8% (range, 0-7%) of the target volume was underdosed with the 95% isodose level for the 3-D plans compared with 18.8% (range, 2.0-36.6%) for the 2-D plans. This was due to improved identification of the target volumes and better design of blocked fields with beams eye view treatment planning. Furthermore, the mean dose to the opposite parotid was 3.9 Gy for the 3-D plans vs 28.9 Gy for the conventional plans. With a minimum follow-up of 4 months, only 2 of 12 patients have complained of a dry mouth. CONCLUSION These encouraging results suggest that this approach is feasible in many cases. 3-D treatment planning may allow the use of parotid sparing techniques in patients who otherwise would not have been considered candidates using conventional radiotherapy techniques.