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.     

Importance of the initial volume of parotid glands in xerostomia for patients with head and neck cancers treated with IMRT

OBJECTIVE: Our aim was to evaluate predictors of xerostomia in patients with head and neck cancers treated with intensity-modulated radiation therapy (IMRT). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

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

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

Intensity-modulated radiotherapy significantly reduces xerostomia compared with conventional radiotherapy

PURPOSE: Xerostomia is a severe complication after radiotherapy for oropharyngeal cancer, as the salivary glands are in close proximity with the primary tumor. Intensity-modulated radiotherapy (IMRT) offers theoretical advantages for normal tissue sparing. A Phase II study was conducted to determine the value of IMRT for salivary output preservation compared with conventional radiotherapy (CRT). METHODS AND MATERIALS: A total of 56 patients with oropharyngeal cancer were prospectively evaluated. Of these, 30 patients were treated with IMRT and 26 with CRT. Stimulated parotid salivary flow was measured before, 6 weeks, and 6 months after treatment. A complication was defined as a stimulated parotid flow rate <25% of the preradiotherapy flow rate. RESULTS: The mean dose to the parotid glands was 48.1 Gy (SD 14 Gy) for CRT and 33.7 Gy (SD 10 Gy) for IMRT (p < 0.005). The mean parotid flow ratio 6 weeks and 6 months after treatment was respectively 41% and 64% for IMRT and respectively 11% and 18% for CRT. As a result, 6 weeks after treatment, the number of parotid flow complications was significantly lower after IMRT (55%) than after CRT (87%) (p = 0.002). The number of complications 6 months after treatment was 56% for IMRT and 81% for CRT (p = 0.04). CONCLUSIONS: IMRT significantly reduces the number of parotid flow complications for patients with oropharyngeal cancer.     

Intensity modulated radiotherapy for head and neck cancer: evidence for preserved salivary gland function.

BACKGROUND AND PURPOSE: To investigate the salivary gland function following intensity modulated radiotherapy (IMRT) for head and neck cancer. PATIENTS AND METHODS: Seventeen patients with oropharyngeal (n=11) or nasopharyngeal (n=6) carcinoma located adjacent to the major salivary glands were treated with IMRT with an emphasis to spare the salivary glands from high-dose irradiation and to reduce the risk of postirradiation xerostomy. Three patients had stage 2, 4 stage III, and 10 stage IVA cancer. The total basal and stimulated saliva flow rates were measured before the treatment, and 6 and 12 months after radiotherapy. RESULTS: The median basal saliva flow rate measured before radiation treatment was 0.13 mL/min, and at 6 and 12 months after the completion of IMRT 0.04 mL/min and 0.07 mL/min, respectively. The corresponding median stimulated saliva flow rates were 0.49 mL/min, 0.33 mL/min, and 0.45 mL, respectively. The D50 for an impaired stimulated parotid gland saliva flow rate was 25.5 Gy. Only two (12%) patients developed grade 3 and none grade 4 xerostomia during a median follow-up of 24 months (range, 12-40 months). No patients had locoregional cancer recurrence following IMRT. CONCLUSIONS: The results suggest that much of the salivary gland function can be maintained with IMRT without jeopardizing the local control rate in the treatment of locally advanced oropharynx or nasopharynx carcinoma.     

Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy

PURPOSE: To evaluate salivary gland function after inversely planned stereotactic intensity-modulated radiotherapy (IMRT) for tumors of the head-and-neck region using quantitative pertechnetate scintigraphy. METHODS AND MATERIALS: Since January 2000, 18 patients undergoing IMRT for cancer of the head and neck underwent pre- and posttherapeutic scintigraphy to examine salivary gland function. The mean dose to the primary planning target volume was 61.5 Gy (range 50.4-73.2), and the median follow-up was 23 months. In all cases, the parotid glands were directly adjacent to the planning target volume. The treatment planning goal was for at least one parotid gland to receive a mean dose of <26 Gy. Two quantitative parameters (change in maximal uptake and change in the relative excretion rate before and after IMRT) characterizing the change in salivary gland function after radiotherapy were determined. These parameters were compared with respect to the dose thresholds of 26 and 30 Gy for the mean dose. In addition, dose-response curves were calculated. RESULTS: Using IMRT, it was possible in 16 patients to reduce the dose for at least one parotid gland to < or =26 Gy. In 7 patients, protection of both parotid glands was possible. No recurrent disease adjacent to the protected parotid glands was observed. Using the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer scoring system, only 3 patients had Grade 2 xerostomia. No greater toxicity was seen for the salivary glands. The change in the relative excretion rate was significantly greater, if the parotid glands received a mean dose of > or =26 Gy or > or =30 Gy. For the change in maximal uptake, a statistically significant difference was seen only for the parotid glands and a dose threshold of 30 Gy. For the end point of a reduction in the parotid excretion rate of >50% and 75%, the dose-response curves yielded a dose at 50% complication probability of 34.8 +/- 3.6 and 40.8 +/- 5.3 Gy, respectively. CONCLUSION: Using IMRT, it is possible to protect the parotid glands and reduce the incidence and severity of xerostomia in patients. Doses <26-30 Gy significantly preserve salivary gland function. The results support the hypothesis that application of IMRT does not lead to increased local failure rates.     

Sparing of the submandibular glands by intensity modulated radiotherapy in the treatment of head and neck cancer.

BACKGROUND AND PURPOSE: The submandibular glands produce most of the unstimulated saliva output and are the key in prevention of radiation-related xerostomia. We investigated whether sparing of the submandibular function is feasible with intensity modulated radiotherapy (IMRT). PATIENTS AND METHODS: Thirty-six patients diagnosed with head and neck cancer were treated with IMRT and had at least one parotid gland excluded from the planning target volume. In a subset, of these patients (n=18) where the risk of cancer recurrence in the contralateral submandibular region was judged low, the contralateral submandibular gland was spared from full-dose irradiation. The total unstimulated and stimulated salivary flow rates and adverse effects were monitored. RESULTS: Twelve months following IMRT mean unstimulated saliva flow was 60% of the baseline value among patients who had one submandibular gland spared and 25% among those who did not (P=0.006). Patients whose contralateral submandibular was spared reported less grade two or three xerostomia (4 vs. 11; P=0.018), and used less saliva substitutes. No cancer recurrences were detected at the vicinity of the spared glands during a median follow-up time of 31 months. CONCLUSIONS: Submandibular gland sparing with IMRT is safe in selected patients treated for head and neck cancer. It is effective in prevention of radiation-associated xerostomia.     

Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer.

PURPOSE: To determine the relationships between the three-dimensional dose distributions in parotid glands and their saliva production, and to find the doses and irradiated volumes that permit preservation of the salivary flow following irradiation (RT). METHODS AND MATERIALS: Eighty-eight patients with head and neck cancer irradiated with parotid-sparing conformal and multisegmental intensity modulation techniques between March 1994 and August 1997 participated in the study. The mean dose and the partial volumes receiving specified doses were determined for each gland from dose-volume histograms (DVHs). Nonstimulated and stimulated saliva flow rates were selectively measured from each parotid gland before RT and at 1, 3, 6, and 12 months after the completion of RT. The data were fit using a generalized linear model and the normal tissue complication probability (NTCP) model of Lyman-Kutcher. In the latter model, a "severe complication" was defined as salivary flow rate reduced to < or =25% pre-RT flow at 12 months. RESULTS: Saliva flow rates data were available for 152 parotid glands. Glands receiving a mean dose below or equal to a threshold (24 Gy for the unstimulated and 26 Gy for the stimulated saliva) showed substantial preservation of the flow rates following RT and continued to improve over time (to median 76% and 114% of pre-RT for the unstimulated and stimulated flow rates, respectively, at 12 months). In contrast, most glands receiving a mean dose higher than the threshold produced little saliva with no recovery over time. The output was not found to decrease as mean dose increased, as long as the threshold dose was not reached. Similarly, partial volume thresholds were found: 67%, 45%, and 24% gland volumes receiving more than 15 Gy, 30 Gy, and 45 Gy, respectively. The partial volume thresholds correlated highly with the mean dose and did not add significantly to a model predicting the saliva flow rate from the mean dose and the time since RT. The NTCP model parameters were found to be TD50 (the tolerance dose for 50% complications rate for whole organ irradiated uniformly) = 28.4 Gy, n (volume dependence parameter) = 1, and m (the slope of the dose/response relationship) = 0.18. Clinical factors including age, gender, pre-RT surgery, chemotherapy, and certain medical conditions were not found to be significantly associated with the salivary flow rates. Medications (diuretics, antidepressants, and narcotics) were found to adversely affect the unstimulated but not the stimulated flow rates. CONCLUSIONS: Dose/volume/function relationships in the parotid glands are characterized by dose and volume thresholds, steep dose/response relationships when the thresholds are reached, and a maximal volume dependence parameter in the NTCP model. A parotid gland mean dose of < or =26 Gy should be a planning goal if substantial sparing of the gland function is desired.     

Quality of life after parotid-sparing IMRT for head-and-neck cancer: a prospective longitudinal study

PURPOSE: Parotid-sparing intensity-modulated radiotherapy (IMRT) for head-and-neck cancer reduces xerostomia compared with standard RT. To assess potential improvements in broader aspects of quality of life (QOL), we initiated a study of patient-reported QOL and its predictors after IMRT. MATERIALS AND METHODS: This was a prospective longitudinal study of head-and-neck cancer patients receiving multisegmental static IMRT. Patients were given a validated xerostomia questionnaire (XQ), and a validated head-and-neck cancer-related QOL questionnaire consisting of four multi-item domains: Eating, Communication, Pain, and Emotion. The Eating domain contains one question (total of six) asking directly about xerostomia. In both questionnaires, higher scores denote worse symptoms or QOL. The questionnaires and measurements of salivary output from the major glands were completed before RT started (pre-RT) and at 3, 6, and 12 months after RT. The association between the QOL scores and patient-, tumor-, and therapy-related factors was assessed using the random effects model. RESULTS: Thirty-six patients participating in the study completed the questionnaires through 12 months. The XQ scores worsened significantly at 3 months compared with the pre-RT scores, but later they improved gradually through 12 months (p = 0.003), in parallel with an increase in the salivary output from the spared salivary glands. The QOL summary scores were stable between the baseline (pre-RT) and 3 months after RT scores. Patients receiving postoperative RT (whose pre-RT questionnaires were taken a few weeks after surgery) tended to have improved scores after RT, reflecting the subsidence of acute postoperative sequelae, compared with a tendency toward worsened scores in patients receiving definitive RT. After 3 months, statistically significant improvement was noted in the summary QOL scores for all patients, through 12 months after RT (p = 0.01). The salivary flow rates, tumor doses, mean oral cavity dose, age, gender, sites or stages of tumor, surgery, and use of chemotherapy were not associated with the QOL scores at any point. The mean dose to the parotid glands correlated with the QOL scores at 3 months (p = 0.05) but not at other post-RT periods. The XQ and QOL summary scores did not correlate before RT but were significantly correlated at each post-RT point (p < 0.01), with a linear correlation coefficient (r) of 0.59, 0.72, and 0.67 at 3, 6, and 12 months, respectively. At these points, the XQ scores also correlated significantly with the scores of each of the individual QOL domains (p < or = 0.01), including the domains Pain and Emotion, which did not contain any xerostomia-related question. CONCLUSION: After parotid-sparing IMRT, a statistically significant correlation was noted between patient-reported xerostomia and each of the domains of QOL: Eating, Communication, Pain, and Emotion. Both xerostomia and QOL scores improved significantly over time during the first year after therapy. These results suggest that the efforts to improve xerostomia using IMRT may yield improvements in broad aspects of QOL.     

Intensity-modulated radiation therapy for head and neck cancers with bilateral irradiation of the neck : preliminary results]

PURPOSE: To report preliminary results of a prospective study of intensity-modulated radiotherapy (IMRT) for head and neck squamous cell carcinoma (HNC) with bilateral irradiation of the neck. PATIENTS AND METHODS: At the Alexis Vautrin Cancer Center, 23 patients have been treated with IMRT for HNC since January 2002-August 2003. The first 10 patients with a minimum follow-up of 3 months were analyzed. All tumors were oropharyngeal. There were four females and six males, with a mean age of 50 years (range 39-66). Stages were I-II in eight and III-IV in two. CTV1 was microscopic disease and N0 neck (prescribed dose : 50 Gy) and CTV2 was macroscopic disease and the volume at risk (prescribed dose: 66-70 Gy). PTV were CTV + 5 mm. Patient's immobilization consisted of a five-point head neck shoulder thermoplastic mask. Set-up verifications were done by semi-automatically matching portal images and digitized reconstructed radiographs. IMRT used dynamic multileaf collimation. Five patients (group A) received 50 Gy IMRT (two post-operative and three with a brachytherapy boost with a mean dose: 27.5 Gy), and five patients (group B) received 66-70 Gy IMRT (four post-operative). Acute and late normal tissue effects were graded according to the RTOG-EORTC radiation morbidity scoring criteria. RESULTS: With a median follow-up of 7.4 months (range 3-18.5), no patient died or had loco-regional relapse. The displacements were <4 mm in 98% cases. CTV1 and 2 received 95% of the prescribed dose in 100% of the volume. On average the mean dose to the contralateral parotid was 25.5 Gy for group A vs. 31 Gy for group B (P = 0.09). Mean doses <26 Gy were obtained in three of five patients in group A vs. zero of five patients in group B (P = 0.04). Acute skin toxicities were grade 1 in five patients, grade 2 in four and grade 3 in one. Acute mucositis cases were grade 1 in three patients, grade 2 in five and localized grade 3 in two. At 3 months, 50% of the patients had a grade 0-1 late xerostomia. CONCLUSION: The 26 Gy dose limit constraint to the contralateral parotid was easier to satisfy when IMRT was prescribed at a maximum dose of 50 Gy. Acute toxicity is low. The displacements in the mask indicate that it is possible to define the PTV as CTV + 4 mm. This reduction should decrease the mean dose to the parotids. At 3 months, a 50% rate of grade 0-1 late xerostomia encourages the hope of a very low rate at 2 years.     

Dose and volume impact on radiation-induced xerostomia

Radiation-induced xerostomia consists in the chronic dryness of the mouth caused by parotid gland irradiation. Parotid glands produce approximately 60% of saliva while the rest is secreted by submandibular and accessory salivary glands. Methods of measuring the salivary output are essentially represented by 99mTc-pertechnate scintigraphy or simpler albeit less accurate methods in stimulated or unstimulated saliva. There are subjective and objective criteria of classification and grading of the secretion of saliva. Radiation-induced xerostomia, namely the residual salivary gland function is evidently associated with the mean dose absorbed. The salivary output tends to decrease after the end of radiotherapy. The partial dose-volume is substantially correlated with the mean dose to the whole gland. As for ipsilateral irradiation for head and neck cancer, conformal RT or IMRT allow to spare the contralateral parotid gland without increasing the risk of contralateral nodal recurrences. The monitoring system of late toxicity used by the authors is presented.     

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.     

Dynamic intensity-modulated non-coplanar arc radiotherapy (INCA) for head and neck cancer.

BACKGROUND AND PURPOSE: To define the potential advantages of intensity-modulated radiotherapy (IMRT) applied using a non-coplanar dynamic arc technique for the treatment of head and neck cancer. MATERIALS AND METHODS: External beam radiotherapy (EBRT) was planned in ten patients with head and neck cancer using coplanar IMRT and non-coplanar arc techniques, termed intensity modulated non-coplanar arc EBRT (INCA). Planning target volumes (PTV1) of first order covered the gross tumor volume and surrounding clinical target volume treated with 68-70 Gy, whereas PTV2 covered the elective lymph nodes with 54-55 Gy using a simultaneous internal boost. Treatment plan comparison between IMRT and INCA was carried out using dose-volume histogram and "equivalent uniform dose" (EUD). RESULTS: INCA resulted in better dose coverage and homogeneity of the PTV1, PTV2, and reduced dose delivered to most of the organs at risk (OAR). For the parotid glands, a reduction of the mean dose of 2.9 (+/- 2.0) Gy was observed (p = 0.002), the mean dose to the larynx was reduced by 6.9 (+/- 2.9) Gy (p = 0.003), the oral mucosa by 2.4 (+/- 1.1) Gy (p < 0.001), and the maximal dose to the spinal cord by 3.2 (+/- 1.7) Gy (p = 0.004). The mean dose to the brain was increased by 3.0 (+/- 1.4) Gy (p = 0.002) and the mean lung dose increased by 0.2 (+/- 0.4) Gy (p = 0.87). The EUD suggested better avoidance of the OAR, except for the lung, and better coverage and dose uniformity were achieved with INCA compared to IMRT. CONCLUSION: Dose delivery accuracy with IMRT using a non-coplanar dynamic arc beam geometry potentially improves treatment of head and neck cancer.     

Sparing the parotid glands and surgically transferred submandibular gland with helical tomotherapy in post-operative radiation of head and neck cancer: a planning study.

BACKGROUND AND PURPOSE: To evaluate the feasibility of sparing the parotid glands and surgically transferred submandibular gland (SMG) by intensity modulated radiotherapy (IMRT) in post-operative cases of head and neck cancer (HNC). MATERIALS AND METHODS: Ten patients (larynx-2, base of tongue-4, tonsil-3, and unknown primary-1; pathologic stages III-IV) who underwent SMG transfers on the side of N0 neck along with definitive surgery were selected for this study. IMRT planning was done retrospectively using helical tomotherapy approach. Planning objective was to deliver 60 Gy to PTV1 and 54 Gy to PTV2 while maintaining the mean dose to the total parotid volume (TPV) and SMG less than 26 Gy. RESULTS: The mean dose (+/-SD) to the TPV and SMG were 25+/-0.6 Gy and 23+/-1.9 Gy, respectively. The D(95) for PTV1 and PTV2 were 59.9+/-0.1 Gy and 54.9+/-0.3 Gy, respectively, satisfying our planning goal for PTV coverage. The D(99) for PTV1 and PTV2 were 58.2+/-0.7 Gy and 49.5+/-2.2 Gy, respectively, showing that sparing the salivary glands did not result in underdosing of the PTVs. CONCLUSIONS: By combining the gland transfer and IMRT, the mean dose to TPV and transferred SMG could be reduced to less than 26 Gy in post-operative patients of HNC.     

Intensity-modulated radiotherapy: Is xerostomia still prevalent?

Conformal radiation with intensity-modulated radiotherapy (IMRT) is a technique that potentially can minimize the dose to salivary glands and thereby decrease the incidence of xerostomia. Precise target determination and delineation is most important when using salivary gland-sparing techniques of IMRT. Reduction of xerostomia can be achieved by sparing the salivary glands on the uninvolved oral cavity and keeping the mean parotid gland dose of less than 26 to 30 Gy as a planning criterion if the treatment of disease is not compromised and parotid function preservation is desired.     

Protection of salivary function by concomitant pilocarpine during radiotherapy: a double-blind, randomized, placebo-controlled study

PURPOSE: To investigate the effect of concomitant administration of pilocarpine during radiotherapy for head-and-neck squamous cell carcinoma (HNSCC) on postradiotherapy xerostomia. METHODS AND MATERIALS: A prospective, double blind, placebo-controlled randomized trial including 170 patients with HNSCC was executed to study the protective effect of pilocarpine on radiotherapy-induced parotid gland dysfunction. The primary objective endpoint was parotid flow rate complication probability (PFCP) scored 6 weeks, 6 months, and 12 months after radiotherapy. Secondary endpoints included Late Effects of Normal Tissue/Somatic Objective Management Analytic scale (LENT SOMA) and patient-rated xerostomia scores. For all parotid glands, dose-volume histograms were assessed because the dose distribution in the parotid glands is considered the most important prognostic factor with regard to radiation-induced salivary dysfunction. RESULTS: Although no significant differences in PFCP were found for the two treatments arms, a significant (p = 0.03) reduced loss of parotid flow 1 year after radiotherapy was observed in those patients who received pilocarpine and a mean parotid dose above 40 Gy. The LENT SOMA and patient-rated xerostomia scores showed similar trends toward less dryness-related complaints for the pilocarpine group. CONCLUSIONS: Concomitant administration of pilocarpine during radiotherapy did not improve the PFCP or LENT SOMA and patient-rated xerostomia scores. In a subgroup of patients with a mean dose above 40 Gy, pilocarpine administration resulted in sparing of parotid gland function. Therefore, pilocarpine could be provided to patients in whom sufficient sparing of the parotid is not achievable.     

Optimisation of conformal radiation therapy by intensity modulation: cancer of the larynx and salivary gland function.

PURPOSE: Prevention of damage to critical normal tissues is of paramount importance for the quality of life of patients irradiated for cancers in the head and neck. The purpose of this paper was to evaluate the parotid gland sparing 3D conformal radiation therapy technique (3DCRT) in a prospective study in node negative cancer of the larynx. MATERIALS AND METHODS: Twenty-six patients with node negative squamous cell cancer of the larynx were irradiated by a 3DCRT technique (class solution) to both sides of the neck (elective dose 46 Gy to levels II, III and IV) and primary tumour (70 Gy). Dose distributions of the major salivary glands were correlated with objective (stimulated whole saliva flow, WS) and subjective (questionnaire; visual analogue scale, VAS) salivary gland function. Apart from the clinically used 3DCRT technique, in order to optimise 3DCRT dose distributions, intensity modulated (IMRT) treatment plans were generated for the same patient population. Dose-volume histograms of 3DCRT and IMRT treatment plans were analysed and compared. RESULTS: For the 26 patients irradiated with the 3DCRT class solution technique: VAS scores and questionnaires reached their nadir 3 months post-radiotherapy; WS reached its nadir 6 months post-radiotherapy. WS flow rates improved significantly, but never normalised; 2 years post-treatment WS measurements were 48% of the pre-treatment values. VAS scores deteriorated during ERT from 0 pre-treatment to 6.1 immediately post-treatment. Compared to pre-treatment, questionnaires were answered affirmative by increasing numbers of patients. For all patients, IMRT treatment plans resulted in a significant reduction of the dose delivered to the parotid glands compared to the 3DCRT-treatment technique. CONCLUSIONS: The class solution for the 3DCRT salivary gland sparing technique is inadequate for fully preserving salivary gland function, given the dose distributions (DVHs) as well as the subjective- and objective salivary gland function assessments. The results can be optimised in the future, that is a further reduction of xerostomia can be achieved, by using IMRT techniques focused at sparing major and minor salivary glands.     

Dose de tolérance à l’irradiation des tissus sains : les glandes salivaires

Xerostomia is one of the most a common complication of radiotherapy for head and neck cancers, affecting quality of life. Parotid glands produce approximately 60% of saliva and submandibular glands 20% of saliva while the rest is secreted by sublingual and accessory salivary glands. Methods of measuring the salivary output are collection of unstimulated or stimulated saliva or 99mTc-pertechnate scintigraphy. Several studies demonstrated that late salivary dysfunction after radiotherapy has been correlated to the mean parotid gland dose, with recovery occurring with time. Severe xerostomia could be avoided if at one parotid gland is spared to a mean dose of less than approximately 25–30 Gy. Clinical benefit of submandibular gland sparing is more controversial. A mean dose less than 39 Gy could preserve submandibular gland function. This paper aims to review main studies evaluating tolerance dose of salivary glands.     

Effect of pilocarpine during radiation therapy: results of RTOG 97-09, a phase III randomized study in head and neck cancer patients

Radiation therapy is an important curative modality in the treatment of patients with head and neck cancer. However, radiation-induced changes in the oral cavity, such as xerostomia and mucositis, are among the most debilitating treatment sequelae experienced by patients undergoing radiation therapy, and attempts at ameliorating these side effects have been poor at best. Pilocarpine has been approved for post-radiation xerostomia, and the effect of its use during radiation therapy on salivary flow, xerostomia, mucositis, and quality of life (QOL) was assessed in a phase III study conducted by the Radiation Therapy Oncology Group (RTOG 97-09). In total, 245 evaluable patients were randomized to pilocarpine or placebo. Selected patients were required to have > or = 50% of the volume of the major salivary glands receive > or = 50Gy; to agree to provide stimulated and unstimulated samples of saliva (measured in g) before treatment, at the end of treatment, and 3 and 6 months after completion of radiation therapy; and to complete the University of Washington Head and Neck Symptom Scale. Following the completion of radiation therapy, the average unstimulated salivary flow was statistically greater in the pilocarpine group, whereas no difference was noted following parotid stimulation. There was no effect on the amelioration of mucositis. The results of the QOL scales did not reveal any significant difference between the pilocarpine and placebo groups with regard to xerostomia and mucositis. The significant difference in unstimulated salivary flow supports the concomitant use of oral pilocarpine to decrease radiation-associated xerostomia. However, the absent correlation between improved salivary flow and QOL scores is of some concern (though not a new finding) and may be related to the existence of comorbidities and the lack of effect on mucositis.