Parotid Gland Volume Research Articles

Radiation‐induced volume changes in parotid and submandibular glands in patients with head and neck cancer receiving postoperative radiotherapy: A longitudinal study

To investigate changes in parotid and submandibular gland volumes of patients with head and neck cancer treated with postoperative intensity-modulated radiotherapy (IMRT) or conventional radiotherapy (CRT), and to relate the volume changes to different mean radiation therapy (RT) doses to the parotid and submandibular glands. Between May 2007 and May 2008, 82 head and neck cancer patients (oral cavity cancer, 71; oropharynx cancer, 11) were treated with surgery and postoperative RT (IMRT, 40; CRT, 42) at our institution. Every patient underwent four computed tomography (CT) scans: one before RT, one after 3 weeks or at the 15th fraction of RT, one upon completing RT, and one at 2 months after RT; 39 of 82 patients had an additional CT scan at 6 months after RT. A dose-volume histogram was used to evaluate the mean volumes of patients' parotid and submandibular glands and mean RT doses to the glands on every CT scan. Altogether, 241 salivary glands (parotid, 162; submandibular, 79) were analyzed. The volume changes of the glands were evaluated against three levels of mean gland doses: <30 Gy, 30 to 50 Gy, and >50 Gy. The mean RT doses to spared parotid glands, spared submandibular glands, and irradiated submandibular glands in patients treated with IMRT were 22.21 Gy, 18.26 Gy, and 52.19 Gy, respectively. The mean doses to parotid and submandibular glands in patients treated with CRT were 50.22 Gy and 62.09 Gy, respectively. The average volume loss rates in parotid glands after 3 weeks of RT, at the end of RT, and 2 months after RT versus before RT were 20.01%, 26.93%, and 27.21%, respectively. The average volume loss rates in submandibular glands after 3 weeks of RT, at the end of RT, and 2 months after RT versus before RT was 11.49%, 16.76%, and 16.29%, respectively. Parotid and submandibular glands did not continue to shrink after completing RT. We observed more volume loss during RT in the parotid glands than in the submandibular glands. The average rates of volume loss during the first 3 weeks of RT (20.01% and 11.49%, respectively) were larger than in the last 3 weeks of RT (8.57% and 6.0%, respectively). No significant differences were observed in the mean volumes of both parotid and submandibular glands between the end of RT, 2 months post-RT, and 6 months post-RT (P > .05). Volume loss at higher doses (>30 Gy) to the glands was significantly larger than at low doses (<30 Gy; P < .001). The parotid and submandibular glands shrunk during RT, but the parotid glands shrunk more than the submandibular glands. These gland volume reductions correlated significantly with the mean dose to the irradiated glands; the spared glands showed few changes.

SU‐FF‐T‐96: Clinical Study of the Necessity of Replanning IMRT Treatment for Patients with Nasopharyngeal Carcinoma

Purpose: To investigate the necessity of replan for patients diagnosed with nasopharyngeal carcinoma (NPC) during IMRT treatment. Method and Materials: Twenty‐eight NPC patients treated with IMRT were selected in this study. The patients were prescribed of 70 to 76 Gy for Gross Tumor Volume (GTV) in 33 fraction treatment. Before the 25th fraction of the treatment, a new simulation CT were acquired for all the patients. GTV, Clinical Target Volume (CTV) and the surrounding critical normal structures in the new CT were manually delineated by the same oncologist for the original plan contouring. The original prescription dose for GTVnx, GTVnd, CTV1, CTV2 was 70∼76Gy, 66∼70Gy, 60∼66Gy, and 56∼60Gy respectively. The target dose distributions in the new CT were obtained after recalculating based on the original plan in CORVUS 6.3 treatment planning system. The doses of the spinal cord and parotid glands in two plans were quantified and compared, as well as for normal critical structures. Results: Significant decrease of the transverse diameter of the nasopharyngeal and the left and right parotid glands volume were observed before the 25th fraction, comparing to the original planning CT (p&lt;0.0001). The mean decreases were 6.60±4.28mm, 4.49±4.77cm3 and 3.44±3.62cm3 respectively. The maximum dose of the spinal cord, mean dose of the left and right parotid were increased significantly at the 25th fraction (p&lt;0.01). The mean of the increased dose were 5.18±8.41Gy, 4.15±9.21Gy and 5.29±9.278Gy respectively. Based on dose constraint criterion in the RTOG0225 protocol, the dose of the normal critical structures for 50%(14/28) of the regenerated plans were out of limit comparing to 3%(1/28) of the original plans (p&lt;0.0001). Conclusion: Based on our observation, it is necessary to replan for patients with NPC to cover the targets and spare normal critical structures.

Modeling of Salivary Production Recovery After Radiotherapy Using Mixed Models: Determination of Optimal Dose Constraint for IMRT Planning and Construction of Convenient Tools to Predict Salivary Function

The mathematical relationship between the dose to the parotid glands and salivary gland production needs to be elucidated. This study, which included data from patients included in a French prospective study assessing the benefit of intensity-modulated radiotherapy (RT), sought to elaborate a convenient and original model of salivary recovery. Between January 2001 and December 2004, 44 patients were included (35 with oropharyngeal and 9 with nasopharyngeal cancer). Of the 44 patients, 24 were treated with intensity-modulated RT, 17 with three-dimensional conformal RT, and 2 with two-dimensional RT. Stimulated salivary production was collected for </=24 months after RT. The data of salivary production, time of follow-up, and dose to parotid gland were modeled using a mixed model. Several models were developed to assess the best-fitting variable for the dose level to the parotid gland. Models developed with the dose to the contralateral parotid fit the data slightly better than those with the dose to both parotids, suggesting that contralateral and ipsilateral parotid glands are not functionally equivalent even with the same dose level to the glands. The best predictive dose-value variable for salivary flow recovery was the volume of the contralateral parotid gland receiving >40 Gy. The results of this study show that the recommendation of a dose constraint for intensity-modulated RT planning should be established at the volume of the contralateral parotid gland receiving >40 Gy rather than the mean dose. For complete salivary production recovery after 24 months, the volume of the contralateral parotid gland receiving >40 Gy should be <33%. Our results permitted us to establish two convenient tools to predict the saliva production recovery function according to the dose received by the contralateral parotid gland.

Salivary gland biometry in female patients with eating disorders

High-resolution greyscale ultrasound is a generally accepted diagnostic tool for salivary gland enlargement, although no standard biometrical data for the sizes of unaffected parotid and submandibular glands exist. A lot of case reports describe non-inflammatory swelling of salivary glands as symptoms of eating disorders like anorexia nervosa or bulimia nervosa. They might be the only visible sign for the disease. With our prospective study we tried to quantify and compare biometrically the salivary gland in eating disordered patients, obese and normal-weight, healthy controls. A total of 70 females between 16 and 40 years of age were included of which 25 were healthy controls. All subjects underwent three-dimensional high resolution B-scan sonography of the parotid and submandibular gland. Gland volumes were calculated and a multiple regression analysis was done to investigate the influence of an eating disorder on salivary gland size. A significant difference in the size of the parotid glands was seen between our three study groups of adipose and eating disordered patients and healthy, normal-weight controls. The parotid gland volumes were seen in the subgroup bulimia nervosa (BN), (parotid volume = 63,708 mm(3)) where the mean value was more than twice as high as in the control group (31,059 mm(3)). By using body mass index and group characteristic the parotid gland volume as the dependent variable could be estimated with an r (2) of 0.327 in multiple regression analysis. Only the parotid glands were significantly enlarged, while the submandibular glands show no signs of enlargement. Eating disorders influence size of parotid glands, still the factors and the pathogenesis leading to this enlargement seem to be different in adiposity on the one and different types of eating disorders on the other hand. Standard gland volumes could be established, comparable to former initial reports. Submandibular gland remains unaffected by these alterations. We could show that high-resolution ultrasound assessment of parotid gland volume adds a complementary quantitative parameter of organ affection in eating disorders (anorexia/bulimia nervosa).

Actual Dose Variation of Parotid Glands and Spinal Cord for Nasopharyngeal Cancer Patients During Radiotherapy

For intensity-modulated radiotherapy of nasopharyngeal cancer, accurate dose delivery is crucial to the success of treatment. This study aimed to evaluate the significance of daily image-guided patient setup corrections and to quantify the parotid gland volume and dose variations for nasopharyngeal cancer patients using helical tomotherapy megavoltage computed tomography (CT). Five nasopharyngeal cancer patients who underwent helical tomotherapy were selected retrospectively. Each patient had received 70 Gy in 35 fractions. Daily megavoltage CT scans were registered with the planning CT images to correct the patient setup errors. Contours of the spinal cord and parotid glands were drawn on the megavoltage CT images at fixed treatment intervals. The actual doses delivered to the critical structures were calculated using the helical tomotherapy Planned Adaptive application. The maximal dose to the spinal cord showed a significant increase and greater variation without daily setup corrections. The significant decrease in the parotid gland volume led to a greater median dose in the later phase of treatment. The average parotid gland volume had decreased from 20.5 to 13.2 cm3 by the end of treatment. On average, the median dose to the parotid glands was 83 cGy and 145 cGy for the first and the last treatment fractions, respectively. Daily image-guided setup corrections can eliminate significant dose variations to critical structures. Constant monitoring of patient anatomic changes and selective replanning should be used during radiotherapy to avoid critical structure complications.

Critical Structure Dose Variation in Daily Treatment of Nasopharyngeal Cancer Patients Based on Helical Tomotherapy Megavoltage CT Images

External beam radiotherapy of nasopharyngeal cancer is complicated by the presence of critical structures near the target volume. With modern image-guided patient setup techniques, dose variation caused by patient positioning uncertainty can be greatly reduced. However, nasopharyngeal cancer patients often incur significant loss of facial mass during treatments primarily due to radiation, whose effect on dose variations to critical structures is not well investigated. This study aims to evaluate this effect using daily helical tomotherapy megavoltage CT (MVCT) images, and to evaluate the magnitude of decrease in parotid gland volume during the course of treatment.

SU-FF-J-108: Dose Variation of Critical Structures in Daily Treatment of Nasopharyngeal Cancer Patients Using Helical Tomotherapy Megavoltage CT System

Purpose: To study daily spinal cord and parotid gland dose variation for nasopharyngeal cancer patients undergoing helical tomotherapy treatments, as a result of patient weight loss during the course of treatments.Method and Materials: Five nasopharygeal cancer patients who received helical tomotherapy treatments were selected. At the end of the treatments, patients lost an average weight of 6.3 kg, or 8.4% relative to the weight at the beginning of the treatments. Daily megavoltage CT (MVCT) scans were performed prior to each treatment fraction, and MVCT images were registered with planning CTimages for patient setup corrections. Contours for spinal cord and parotid glands were drawn on MVCT images throughout the treatment course. Based on daily MVCT images, actual dose delivered to the critical structures were calculated using the Planned Adaptive application in the helical tomotherapy treatment planning system. The maximum dose to the spinal cord and the median doses to the parotid glands were analyzed. Results: The maximum dose to the spinal cord, after setup corrections, did not show significant variation as a result of patient weight loss. However, the median doses to the parotid glands showed significant increase due to facial tissue shrinkage during treatments. The average median dose to the parotid glands for the five patients were 83 cGy for the first treatment fraction, and it was 143 cGy per fraction for the last fraction. The average parotid gland volume decreased from 20.5 cc to 13.2 cc during treatments.Conclusion: Daily patient setup corrections based on MVCT image registrations prevented significant dose variation to the spinal cord due to setup uncertainty. During the course of radiotherapy, as a result of body weight loss, the parotid glands typically receive significantly higher dose compared to the dose dictated in the treatment plan.

Gland size estimation and body mass index improve salivary flow rate assessment

Although some representative studies, each with over 100 subjects, have reported no significant differences in salivary flow rates between males and females, the majority of such studies have reported that flow rates are significantly higher in males. I am not aware of any studies which have reported higher salivary flow rates in females than in males. It would seem reasonable to expect that large salivary glands would be able to produce higher flow rates than small glands. This could not be tested until a method of estimating salivary gland size was developed. The first such method was described by Ericson and Hedin who showed, in 23 cadavers, a high correlation (r = 0.95) between the parotid gland volume and the area on a lateral sialogram. For the submandibular glands, the correlation was lower (0.68). Ericson then reported, for 92 subjects, a high correlation (r = 0.93) between the logarithm of parotid salivary flow rate in response to gustatory stimulation with 10% citric acid and the logarithm of gland area on a lateral sialogram. In a similar study on submandibular glands but using 6% citric acid in 28 subjects, the correlation coefficient was 0.52. The only study not carried out by Ericson’s group in which a sialographic technique was employed confirmed, in 30 subjects, Ericson’s finding of a positive correlation between the maximum parotid salivary flow rate and the size of the gland. A major disadvantage of the sialographic technique for estimating gland volume is that it gives only a two-dimensional view of the gland. In addition, it is expensive to carry out, it exposes the subject to radiation, and it cannot be employed on all the major salivary glands.

Radioprotective effect of amifostine on parotid gland functioning is region dependent

To investigation the protective ability of amifostine during partial irradiation of the rat parotid gland. Single-dose X-ray irradiation was performed by use of collimators with conformal radiation portals for either the 100% volume (15 Gy) or the 50% cranial/caudal partial parotid gland volumes (30 Gy). Amifostine was administered intraperitoneally at a dose of 250 mg per kg body weight, 25 minutes before irradiation. Saliva flow rates, gland weights, and the tissues of the individual lobes were investigated up to 1 year after treatment. A clear protective effect of amifostine was found against loss of saliva flow, the altered appearance of gross morphology, loss of gland weight, and histopathologic changes for the 100% volume gland irradiations and for the 50% volume cranial irradiations but not for the 50% volume caudal irradiations. The protective ability of amifostine is strongly dependent on the irradiated glandular region and observed for later damage only. The major effect of the drug seems to be the prevention of volume effects caused by secondary damage that occurs in shielded parts of the gland. The results of the present study show that understanding of the anatomy and physiology of organs that are to be spared is necessary to ensure optimal preservation of function.

Importance of the Initial Volume of Parotid Glands in Xerostomia for Patients with Head and Neck Cancers Treated with IMRT

Our aim was to evaluate predictors of xerostomia in patients with head and neck cancers treated with intensity-modulated radiation therapy (IMRT). Thirty-three patients with pharyngeal cancer were evaluated for xerostomia after having been treated with IMRT. All patients were treated with whole-neck irradiation of 46-50 Gy by IMRT, followed by boost IMRT to the high-risk clinical target volume to a total dose of 56-70 Gy in 28-35 fractions (median, 68 Gy). For boost IMRT, a second computed tomography (CT-2) scan was done in the third to fourth week of IMRT. Xerostomia was scored 3-4 months after the start of IMRT. The mean doses to the contralateral and ipsilateral parotid glands were 24.0 +/- 6.2 and 30.3 +/- 6.6 Gy, respectively. Among the 33 patients, xerostomia of grades 0, 1, 2 and 3 was noted in one, 18, 12 and two patients, respectively. Although the mean dose to the parotid glands was not correlated with the grade of xerostomia, the initial volume of the parotid glands was correlated with the grade of xerostomia (P = 0.04). Of 17 patients with small parotid glands (< or =38.8 ml) on initial CT (CT-1), 11 (65%) showed grade 2 or grade 3 xerostomia, whereas only three (19%) of 16 patients with larger parotid glands showed grade 2 xerostomia (P < 0.05). The mean volume of the parotid glands on CT-1 was 43.1 +/- 15.2 ml, but decreased significantly to 32.0 +/- 11.4 ml (74%) on CT-2 (P < 0.0001). Initial volumes of the parotid glands are significantly correlated with the grade of xerostomia in patients treated with IMRT. The volume of the parotid glands decreased significantly during the course of IMRT.

Simultaneous integrated boost intensity-modulated radiotherapy for locally advanced head-and-neck squamous cell carcinomas: II—clinical results

Purpose To perform a Phase I radiation dose-escalation trial to determine the maximal tolerable dose (MTD) deliverable to the gross tumor volume (GTV) using an accelerated fractionation with simultaneous integrated boost intensity-modulated radiotherapy regimen with parotid gland sparing as the sole therapy in the treatment of locally advanced head-and-neck squamous cell carcinoma. The primary objective was the definition of the MTD using established criteria of quantifying acute dose-limiting toxicity (DLT). Secondary objectives included analysis of failure patterns, tumor control rates, and toxicity. Methods and materials Between July 1999 and June 2002, eligible patients with bulky Stage II to Stage IVB head-and-neck squamous cell carcinoma, excluding laryngeal primaries, were enrolled. Intensity-modulated radiotherapy was delivered with 6-MV photons using a “sliding-window” technique. Enrollment of 6 patients for each dose level was planned; if DLTs were seen in >2 of 6 patients, the previous dose was to be expanded by an additional 6 patients to confirm that dose level as the MTD. All schedules administered a total of 30 fractions, but with escalating doses per fraction (2.27, 2.36, and 2.46 Gy) to achieve a total dose to the GTV of 68.1, 70.8, and 73.8 Gy, respectively. The remaining target tissues were constrained to receive the same dose in all patients regardless of the GTV dose level. The clinical target volume, defined as tissue within 1 cm around the GTV (at high risk of subclinical disease), received 60 Gy in 30 fractions of 2.0 Gy. The electively irradiated target volume, defined as the clinically uninvolved lymph node-bearing tissues, received 54 Gy in 30 fractions of 1.8 Gy. The parotid glands were spared to the degree possible without compromising target coverage. Acute toxicity was scored weekly using National Cancer Institute Common Toxicity Criteria. DLT was defined as any Grade 4 acute toxicity or any acute toxicity requiring either a dose reduction or a treatment break of >5 treatment days. Results Of 18 men and 2 women (average age, 57 years; range, 37–80 years), 17 presented with oropharyngeal primary tumors, and 1 each with squamous cell carcinoma of the oral cavity, nasopharynx, and hypopharynx. None of the 6 patients at dose level 1, and 2 of the 6 patients initially enrolled at dose level 2, developed DLT. Both patients treated at dose level 3 required a 3-day treatment break and dose reduction after rapid development of Grade 3 toxicity (by Day 15). Six additional confirmatory patients subsequently enrolled at dose level 2 completed treatment without DLT. At least 50% of the total parotid gland volume received <30 Gy in 14 patients (average, 54% of volume), with an average mean dose of 32 Gy. In contrast, ≥50% of the distal parotid gland volume received <25 Gy in 15 patients (average, 63% of volume), with an average mean dose of 24 Gy. With a median follow-up of 20 months from the date of enrollment and 28 months for surviving patients, the actuarial 2-year local control (primary site), regional control (nodal sites), and distant control rate was 76.3%, 66.7%, and 71.8%, respectively. Conclusion Dose level 2, 70.8 Gy in 30 fractions of 2.36 Gy, was defined as the MTD deliverable to the GTV using this accelerated fractionation with simultaneous integrated boost intensity-modulated radiotherapy regimen with parotid gland sparing as the sole treatment for locally advanced head-and-neck squamous cell carcinoma. Adequate parotid sparing was achievable in most cases. Early toxicity, tumor control, and survival rates compared favorably with the outcomes after other accelerated regimens.

Importance of mean dose and initial volume of parotid glands in xerostomia of patients with head and neck cancers receiving imrt

To evaluate the predictors of xerostomia in the treatment of head and neck cancers treated with intensity-modulated radiation therapy (IMRT). Dosimetric parameters of the parotid glands are correlated to the grade of xerostomia. Between December 2000 and December 2003, 25 patients were evaluated for xerostomia after being treated definitively for head and neck cancers with IMRT. Of the 25 patients, 13 were nasopharyngeal cancer (NPC), six oropharyngeal cancers, and six hypopharyngeal cancers. Except for one non-Hodgkin lymphoma of nasopharynx, the remaining 24 tumors were squamous cell carcinomas. All of the patients were treated with whole neck irradiation to 46–50 Gy/23–25 fractions by IMRT, followed by boost IMRT to the GTV and high-risk CTV to a total dose of 66–70 Gy/33–35 fractions (median 68 Gy). For the boost IMRT, second CT-simulation was done for all patients when the patients received a total dose of 30–40 Gy. Most patients were treated by concurrent chemo-radiation therapy. Concurrent cisplatin (60–80mg/m2 x 2–3 times) was given for 10 patients with NPC, and weekly docetaxel of 15/m2 was given for 10 patients with oro-hypopharyngeal cancers. Xerostomia was scored according to the subjective assessment of RTOG/EORTC late salivary gland toxicity when acute mucositis subsided 3–4 months after the start of IMRT. Slight dryness without affecting quality of life correlated to grade-1 toxicity, and moderate dryness requiring a water bottle correlated to grade-2 toxicity. Severe dryness referred to patients with a profound change in quality of life resulting from xerostomia was grade 3. It was possible to reduce the mean dose to the contra-lateral parotid gland to 25.0 Gy ± 6.4 Gy by IMRT. The mean dose to the ipsi-lateral parotid gland was 31.0 Gy ± 6.9 Gy. Among the 25 patients, 15 patients showed grade-1 xerostomia 3–4 months after IMRT, and eight and two patients showed grade-2 and grade-3 toxicities, respectively. Correlation between the grade of xerostomia and various dosimetric parameters were analyzed by the Spearman rank correlation. The mean dose to the contra-lateral parotid gland was significantly correlated to the grade of xerostomia (p = 0.036). Interestingly, parotid glands regressed significantly during the course of IMRT. The mean volume of parotid glands in the initial CT simulation was 44.9 ± 16.3 cc, and it was significantly reduced to 32.5 cc ± 12.1 cc (73%) in the second CT simulation obtained at 3–4th week of IMRT (p < 0.0001). Of the nine patients with small parotid glands of less than 35 cc in the initial CT, four grade-2 and two grade-3 xerostomia (67%) were noted, while only four grade-2 xerostomia (25%) were noted out of the remaining 16 patients with larger parotid glands (p < 0.05). In the treatment of head and neck cancers, IMRT could reduce the dose to the parotid glands resulted in sparing salivary function. The mean dose to the contra-lateral parotid gland and initial volume of the parotid glands are predictors of xerostomia. In addition, volume of parotid glands reduced significantly during the course of IMRT. This means that the dosimetric parameters including mean parotid doses obtained by an initial CT simulation are not accurate enough

Importance of mean dose and initial volume of parotid glands in xerostomia of patients with head and neck cancers receiving imrt

Importance of mean dose and initial volume of parotid glands in xerostomia of patients with head and neck cancers receiving imrt

Preservation of oral health–related quality of life and salivary flow rates after inverse-planned intensity- modulated radiotherapy (IMRT) for head-and-neck cancer

PurposeTo assess whether comprehensive bilateral neck intensity-modulated radiotherapy (IMRT) for head-and-neck cancer results in preserving of oral health–related quality of life and sparing of salivary flow in the first year after therapy. Methods and materialsTwenty-three patients with head-and-neck cancer (primary sites: nasopharynx [5], oral cavity [12], oropharynx [3], and all others [3]) were accrued to a Phase I–II trial. Inverse planning was carried out with the following treatment goals: at least 1 spared parotid gland (defined as the volume of parotid gland outside the planning target volume [PTV]) to receive a median dose of less than 20 Gy; spinal cord, maximum 45 Gy; PTV1 to receive a median dose of 50 Gy; PTV2 to receive a median dose of 60 Gy (postoperative setting, n = 15) or 66–70 Gy (definitive radiotherapy setting, n = 8). Treatment was delivered with 6 and 15 MV photons using a “step-and-shoot” technique on a Varian 2300 EX linac with 120-leaf Millenium MLC. Unstimulated and stimulated whole-mouth salivary flow rates were measured, and patients completed the University of Washington instrument (UWQOL) and a separate xerostomia questionnaire (XQOL) in follow-up. ResultsEarly functional outcome end point data are available at the 1-, 3-, and 12-month follow-up time points for 22, 22, and 18 patients, respectively. The combined mean parotid dose was 30.0 Gy (95% confidence interval: 26.9–33.1). The differences from baseline in mean overall UWQOL scores at 1, 3, and 12 months postradiotherapy were −0.24, 0.32, and 4.28, not significantly different from zero (p = 0.89, p = 0.87, p = 0.13). None of the UWQOL individual domain scores related to oral health (pain, eating-chewing, eating-swallowing, and speech) at 1, 3, or 12 months were significantly different from baseline. Both unstimulated and stimulated whole-mouth flow was variably preserved. Unstimulated salivary flow at 1 and 12 months was inversely correlated with combined mean parotid dose (p = 0.014, p = 0.0007), whereas stimulated salivary flow rates at 3 and 12 months were also correlated with combined mean parotid dose (p = 0.025, p = 0.0016). Combined maximum parotid dose was correlated with unstimulated flow rate at 12 months (p = 0.02, r = −0.56) and stimulated flow rate at 1 and 12 months (p = 0.036, r = −0.45; p = 0.0042, r = −0.66). The proportion of patients reporting total XQOL scores of 0 or 1 (no or mild xerostomia) did not diminish significantly from baseline at 1, 3, or 12 months (p = 0.72, p = 0.51, p = 1.0). Unstimulated and stimulated flow at 1 month was inversely correlated with total XQOL score at 12 months (p = 0.025, p = 0.029). ConclusionsOral health–related quality of life (HRQOL) was highly preserved in the initial 12 months after IMRT, as assessed with separate, validated instruments for xerostomia-specific quality of life and oral HRQOL. In general, patients with better-preserved unstimulated salivary flow rates tended to report lower xerostomia scores. Whole-mouth salivary flow rates post IMRT were inversely correlated with combined mean parotid doses. Longer follow-up is required to assess to what extent HRQOL is favorably maintained.

Qantitative dose-volume response analysis of changes in parotid gland function after radiotheraphy in the head-and-neck region

Purpose: To study the radiation tolerance of the parotid glands as a function of dose and volume irradiated.Methods and Materials: One hundred eight patients treated with primary or postoperative radiotherapy for various malignancies in the head-and-neck region were prospectively evaluated. Stimulated parotid flow rate was measured before radiotherapy and 6 weeks, 6 months, and 1 year after radiotherapy. Parotid gland dose-volume histograms were derived from CT-based treatment planning. The normal tissue complication probability model proposed by Lyman was fit to the data. A complication was defined as stimulated parotid flow rate <25% of the preradiotherapy flow rate.Results: The mean stimulated preradiotherapy flow rate of 174 parotid glands was 0.34 mL/min. The mean flow rate reduced to 0.12 mL/min 6 weeks postradiotherapy, but recovered to a mean flow rate of 0.20 mL/min at 1 year after radiotherapy. Reduction in postradiotherapy flow rate correlated significantly with mean parotid dose. No threshold dose was found. Increasing the irradiated volume of parotid glands from 0%–40% to 90–100% in patients with a mean parotid dose of 35–45 Gy resulted in a decrease in flow ratio from, respectively, approximately 100% to less than 10% 6 weeks after radiation. The flow ratio of the 90%–100% group partially recovered to 15% at 6 months and to 30% at 1 year after radiotherapy. The normal tissue complication probability model parameter TD50 (the dose to the whole organ leading to a complication probability of 50%) was found to be 31, 35, and 39 Gy at 6 weeks, 6 months, and 1 year postradiotherapy, respectively. The volume dependency parameter n was around 1, which means that the mean parotid dose correlates best with the observed complications. There was no steep dose-response curve (m = 0.45 at 1 year postradiotherapy).Conclusions: This study on dose/volume/parotid gland function relationships revealed a linear correlation between postradiotherapy flow ratio and parotid gland dose and a strong volume dependency. No threshold dose was found. Recovery of parotid gland function was shown at 6 months and 1 year after radiotherapy. In radiation planning, attempts should be made to achieve a mean parotid gland dose at least below 39 Gy (leading to a complication probability of 50%).

Three-dimensional dosimetric evaluation of a conventional radiotherapy technique for treatment of nasopharyngeal carcinoma

Background and purpose: The aim of this study is to evaluate and delineate the deficiencies in conventional two-dimensional (2-D) radiotherapy planning of nasopharyngeal carcinoma (NPC) treatment and to explore the means for improvement of the existing treatment technique aiming at enhancing local tumor control and reducing treatment complications.Methods and materials: Ten patients with NPC sparing the skull base and without intracranial extension or cranial nerve(s) palsy were chosen in the present study. Two sets of CT images for Phases I and II of the radiotherapy treatment were taken with patient immobilized in the flexed-head and the extended-head positions, respectively. Based on the CT images and endoscopic findings, the gross tumor volume (GTV) was defined. The clinical target volume (CTV) circumscribing the GTV was defined according to Ho's (Halnan, K.E. (ed.) Treatment of Cancer. London: Chapman and Hall, 1982. pp. 249–268) description of the organs at risk of tumor infiltration. The planning target volume (PTV) was defined by adding a margin to the CTV which catered for geometrical inaccuracies. The field borders and shields were set at standard distances from certain bony landmarks and were drawn on the simulator radiograph. Data on the beams and shield arrangements were then transferred to the planning computer via a digitizer. By applying 3-D volumetric dose calculation using a commercial three-dimensional (3D) treatment planning computer, the dose–volume-histograms (DVHs) of GTV, CTV, PTV and critical normal organs were generated for both phases of Ho's treatment technique. The same patients were re-planned using a modified Ho's technique which used 3-D beams-eye-view (BEV) in placing the shielding blocks and the same set of DVHs were generated and compared with those obtained from Ho's technique.Results: The median volumes of GTV, CTV and PTV covered by the 95% isodose in Ho's phase I treatment were around 60%. The dose coverage was unsatisfactory in the superior and inferior and the posterolateral regions. In phase II treatment, the median volume of GTV, CTV and PTV covered by the 95% isodose were 99, 96 and 72%, respectively. Even though the dose coverage of the PTV in both phases of treatment were unsatisfactory, radiotherapy with the original Ho's technique had consistently produced good local control for NPC. However, there is potential room for enhancing the local control further because after modifying Ho's technique by using 3-D BEV customization of the treatment portals, the median volume of the target covered by the 95% isodose was defined as V95. The V95 of the PTV during the Phase II treatment was improved by 13%. The 90% of the volume of temporo-mandibular joints and parotid glands were both irradiated to 53 Gy and 43.6 Gy of the total prescribed dose of 66 Gy, respectively, in phase I and II treatments. With the addition of a hypothalamus-pituitary shield to Ho's technique, 50% of the volume of optic chiasma and temporal lobes received, respectively, 19.3 Gy and 4.5 Gy. However, small volume of the temporal lobes received a maximum dose (Dmax) of 62.8 Gy (95.2% of 66Gy). Most of the brainstem was shielded from the lateral portals but 5% of its volume received a dose ranging from 25.4 to 50.4Gy. The spinal cord (at C1/C2 level) received a Dmax of 40.8 Gy in phase I and of 4.8 Gy in phase II. After modifying Ho's technique by 3-D BEV customization of the treatment portals, the Dmax to the brainstem, the optic chiasma and the temporal lobes could be reduced by 8, 12 and 5%, respectively.Conclusions: Our study indicated that the dose-coverage of the PTV in Ho's radiotherapy technique for the early T-stage NPC was less than satisfactory in the superior and inferior and the posterolateral regions. However, in view of the excellent historical local tumor control with Ho's technique, we have to postulate that the present definition of CTV (and hence the PTV after adding margins to the CTV) lacks clinical significance and can be improved. It appears that the inclusion of the entire sphenoid sinus floor and both medial and lateral pterygoid muscles in the CTV is not necessary for maximal tumor control in the absence of clinical/radiological evidence of tumor infiltration of these organs. Ho's technique can be improved by using 3-D BEV to customize the treatment portals with multileaf collimators or blocks.

CT-based parotid gland location: implications for preservation of parotid function

Purpose: The position of the parotid gland in relation to surrounding structures was investigated.Materials and methods: Sixty-five patients with head and neck tumours were prospectively evaluated. Parotid position was determined using beam's eye views of CT images projected on simulator films. Distances between the different borders of the parotid gland and surrounding bony marks were quantitatively assessed.Results: The parotid gland volume ranged from 12.9 to 46.4 cm3. The distance between the cranial border of the parotid gland and the tuberculum anterior of the atlas ranged between 0.7 and 4.8 cm. The position of the parotid gland was unaffected by the angle of the mandible.Conclusions: The size and position of the parotid gland varies largely among patients. As the extent of radiation-induced salivary dysfunction depends on the volume of the gland tissue exposed, CT-based simulation of radiation fields is necessary.

Intensity-modulated radiation therapy in head and neck cancers: The Mallinckrodt experience.

The purpose of the study was to investigate the feasibility and the optimization of tomotherapy-based intensity-modulated radiation therapy (IMRT) in patients with head and neck cancer. From February 1997 to November 1997, 17 patients with squamous cell carcinoma of the head and neck were treated with IMRT. Patients were immobilized with a noninvasive mask and treated using a serial tomotherapy device on a 6 MV linear accelerator. Treatment planning was performed on a Peacock inverse planning system and prescription optimization was used to achieve the best plan for target coverage and parotid sparing. The treatment planning system process has a dosimetric characteristic of delivering different doses to different target structures simultaneously in each daily treatment; therefore, the biological equivalent dose was implemented using the linear-quadratic model to adjust the total dose to the target volume receiving a daily dose of less than 1.9 Gy. All eight patients with gross disease (six in the nasopharynx, two in the tonsil) and one patient with recurrent nasopharyngeal carcinoma received concurrent cisplatin chemotherapy. Six postoperative patients were treated with irradiation alone. Median follow-up was 2.2 years (range 2.6-1.8 years). All patients completed the prescribed treatment without unexpected interruption. Acute side effects were comparable to those of patients treated with conventional beam arrangements during the same period. No patient required gastrostomy during irradiation. The preliminary experience showed that the noninvasive immobilization mask yielded high positioning reproducibility for our patients. To spare the parotid gland, which is in the proximity of the target, a fraction of the target volume may not receive the prescribed dose. In the best-achievable plan of our studied cohort, only 27% +/- 8% of parotid gland volumes were treated to more than 30 Gy, while an average of 3.3% +/- 0.6% of the target volume received less than 95% of the prescribed dose. This is mainly related to the steep dose gradient in the region where the target abuts the parotid gland. The inverse planning system allowed us the freedom of weighting normal tissue-sparing and target coverage to select the best-achievable plan. Local control was achieved in eight patients with gross tumor; six were treated postoperatively. Of three reirradiated patients, two had symptomatic improvement but persistent disease, and one is without evidence of disease. In summary, a system for patient immobilization, setup verification, and dose optimization for head and neck cancer with parotid sparing without significantly compromising target coverage is being implemented for a tomotherapy-based IMRT plan at the Mallinckrodt Institute of Radiology. The initial clinical experience in tumor control is promising, and no severe adverse acute side effects have been observed. Further refining of delivery technology and the inverse planning system, gaining clinical experience to address target definition and dose inhomogeneity within the targets, and understanding the partial volume effect on normal tissue tolerance are needed for IMRT to excel in the treatment of head and neck cancer. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 92-103, (2000).

Reduction of radiation-induced xerostomia in nasopharyngeal carcinoma using CT simulation with laser patient marking and three-field irradiation technique

Tumor control and reduction of postirradiation xerostomia in patients with nasopharyngeal carcinoma (NPC) using the three-field irradiation technique based on the CT-based simulation with laser patient marking was investigated. Seventy-eight patients with NPC were consecutively treated between 1983 and 1993. In 33 patients treated before 1987, target volume was determined using a conventional x-ray simulator with a reference of CT images, and the primary site was treated by the conventional parallel-opposed two-field technique (Group I). In 45 patients treated from 1987, target volume was determined using a CT simulator slice by slice, the treatment field was projected onto the patient's skin by a laser beam projector mounted on a C-arm, and the primary site was irradiated by a three-fields (anterior and bilateral) technique (Group II). In Group II, the shape of each field was determined using a beam's eye view to reduce the dose to the bilateral parotid glands. The three-field technique reduced the dose to the superficial lobe of parotid gland to about two-thirds of the dose given by the two-field technique. Radiation-induced xerostomia was evaluated by clinical symptoms and radioisotope sialography. The 5-year survival rate and disease-free survival rate were 46.6 and 31.2% in Group I, and 46.8 and 46.5% in Group II. A large variation in the volume of parotid glands were demonstrated, ranging from 9 cm3 to 61 cm3 among patients treated with CT simulation. Forty percent of the patients in Group II showed no or mild xerostomia, whereas all of the patients in Group I showed moderate to severe xerostomia (p < 0.01). The radioisotope sialography study showed that the mean secretion ratio by acid stimulation was improved from 3.8% in the Group I to 15.2% in the Group II (p < 0.01). CT simulation was useful to determine the size and shape of each field to reduce the dose to the parotid gland, of which size varies largely among individual patients. The three-field technique based on CT simulation with laser patient markings is suggested to result in superior complication-free survival in terms of salivary dysfunction than did the conventional two-field technique with x-ray simulatior for NPC.

Influence of radiation therapy on oral Candida albicans colonization: A quantitative assessment

An increase in quantity of oral Candida albicans was documented in patients receiving head and neck radiation therapy during and after therapy, as assessed by an oral-rinse culturing technique. The amount of the increase was greater in denture wearers and directly related to increasing radiation dose and increasing volume of parotid gland included in the radiation portal. A significant number of patients who did not carry C. albicans prior to radiation therapy developed positive cultures by 1 month after radiation therapy. The percentage of patients receiving head and neck radiation therapy who carried C. albicans prior to radiation therapy did not differ significantly from matched dental patient controls.