Combination of submandibular salivary gland transfer and intensity-modulated radiotherapy to reduce dryness of mouth (xerostomia) in patients with head and neck cancer.

BACKGROUND: Xerostomia is a debilitating side effect of radiotherapy for head and neck cancer. Combining surgical submandibular-gland transfer (SMGT) with intensity-modulated radiotherapy (IMRT) may provide greater protection of salivary function. METHODS: This was a single-institution, prospective phase II feasibility trial. Patients with head and neck cancer or unknown primary with neck node metastases received primary surgery with SMGT and postoperative radiotherapy with tomotherapy (60 Gy in 30 fractions). Toxicity and quality of life (QOL) were assessed before surgery, before RT, and after RT. RESULTS: Forty patients received SMGT and IMRT. Only 1 patient experienced grade 3 salivary gland toxicity. At 12 months post-RT, the rate of absent or only mild xerostomia was 89%, and salivary flow rates were approximately 75% of pre-RT levels. CONCLUSIONS: The combination of IMRT with SMGT is feasible and with improved dose constraints may maximally spare the parotid and submandibular glands, leading to decreased xerostomia and improved patient QOL.

Prognostic factors for complete obliteration of arteriovenous malformations treated with LINAC-based stereotactic radiosurgery.

OBJECTIVES: Few series analyzing prognostic fac tors predicting for obliteration of arteriovenous malformations (AVMs) following linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) have been reported. We analyzed prognostic variables, outcomes, and toxicities in 88 patients undergoing LINAC-based SRS for AVMs. METHODS: Following IRB approval, patient records were retrospectively analyzed to identify independent predictors of complete response (obliteration) (CR) and time-to-CR. The majority of AVMs were treated using multiple isocenters and non-coplanar arcs. The median AVM volume was 2.67 cm3 (0.05 - 33.51). Median marginal and maximal doses were 17 (12-24) and 26.1 Gy (15-40), with a median prescription isodose surface of 65%. RESULTS: Spetzler-Martin (SM) grade was determined for 86 patients and was: I-3 pts (3%); II-23 pts (27%); III-45 pts (52%); IV-13 pts (15%); V-2 pts (2%).Of 80 patients with follow-up imaging, 44 (55%) had documented complete responses (CR). Kaplan-Meier estimate probability for CR at 4 years was 62% (95% CI: 0.50, 0.74). Median time to CR was 3 years (95% CI: 2.08, 3.17). Multivariate analysis demonstrated the Spetzler-Martin grade (OR=0.14 for grade III vs. grade I-II; p=0.004 and OR 0.07 for grade IV-V vs. grade I-II; p=0.002) and dichotomized marginal dose > 17 Gy (OR=4.19; p=0.01) to be significantly associated with CR. DISCUSSION: This report demonstrates that for LINAC-based SRS of AVM, marginal dose and Spetzler-Martin grade are strong predictors of complete AVM obliteration.

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.

Phenomenologic model describing flow reduction for parotid gland irradiation with intensity-modulated radiotherapy: evidence of significant recovery effect.

OBJECTIVE: To develop a model describing the relationship between the parotid gland radiation dose and salivary flow reduction. Salivary function was described by the "relative flow reduction" (RFR)-a continuous variable in contrast to the traditional binary response used in normal tissue complication probability estimations. METHODS AND MATERIALS: Twenty-three patients with squamous cell carcinoma of the head and neck who were treated with intensity-modulated radiotherapy (RT) were the subject of this study. Of these patients, 19 had sufficiently long follow-up to be eligible for analysis. All were treated with curative intent, most (14 of 19) in the postoperative setting. The planning objectives were to deliver a mean dose of 50, 60, or 70 Gy, respectively, to low-risk microscopic, high-risk microscopic, and gross disease areas, while maintaining a mean dose of < or =20 Gy to the spared portion of one or both parotid glands. The mean dose to all parotid glands (right and left) was 30.2 Gy. All submandibular glands received >50 Gy when not surgically removed. Whole-mouth saliva collections, including both stimulated and unstimulated saliva flow, were obtained before treatment and at regular intervals after RT. These measurements were converted to the RFR by comparing the posttreatment and pretreatment flow rates. Any follow-up flow rates greater than baseline were scored as 0 relative reduction. We used Lyman's model to relate the equivalent uniform dose to RFR at various points for each patient. The equivalent uniform dose was calculated using the linear quadratic model, with an assumed alpha/beta ratio of 3 Gy for the parotid gland. Measurements were modeled 1-3 months after RT (early) and >6 months after RT (late), and using the best and worst measurements, regardless of when measured. RESULTS: Fitting the Lyman model to RFR data of unstimulated flow revealed a statistically significant dose-complication relationship. We observed a stepwise reduction in flow, with the threshold dose D(50) at 2 Gy per fraction (D(50)) increasing from 12.4 Gy (early) to 43.9 Gy (late). For the worst and best flow measurements, the corresponding D(50) (2 Gy/fr) was 13.0 Gy and 40.1 Gy, respectively. For most stimulated flow measurements, a weak relationship was found between the RFR and equivalent uniform dose. In those cases, the model did not yield a statistically significant description of the data. However, in the case of late measurements, the relationship was statistically significant and similar to that seen in the unstimulated cases, with a D(50) (2 Gy/fr) of 47.5 Gy. CONCLUSION: We observed a strong relationship between the generalized mean parotid gland dose and RFR. The threshold dose increased markedly between the early and late measurements, indicating a statistically significant recovery effect in this tissue. Compared with unstimulated flow, the RFR for stimulated flow was not described as well by the model, because the effect of the stimulant was not included in the model.

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

PURPOSE: To 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 MATERIALS: Twenty-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; PTV(1) to receive a median dose of 50 Gy; PTV(2) 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. RESULTS: Early 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). CONCLUSIONS: Oral 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.

Reduction in radiation dose to lung and other normal tissues using helical tomotherapy to treat lung cancer, in comparison to conventional field arrangements.

The purpose of this study was to determine whether the use of tomotherapy in the treatment of non-small-cell lung cancer (NSCLC) has the potential to reduce radiation dose to normal tissues, in particular, the lungs, esophagus, and spinal cord, as compared with standard radiotherapy. Five patients with anatomically or physiologically inoperable stage III NSCLC were studied, representing a variety of tumor sizes and locations. For each patient, two treatment plans were generated. One was developed using conventional field arrangements (CFA), and the other for tomotherapy. Using dose-volume histogram reduction techniques, including mean normalized dose (NTDmean), V20, and effective uniform dose (EUD), the normal tissue doses for CFA and tomotherapy plans for a given fixed tumor dose were compared. In addition, the maximum tumor doses possible for a given level of mean normalized lung dose were computed and compared for the CFA and tomotherapy plans. The gross tumor volumes in the five patients studied ranged from 13.5 to 87.1 cm. The tumor dose distributions, determined by EUD and minimum dose, were similar for both CFA and tomotherapy plans, as intended. In all cases, the NTDmean of both lungs was significantly reduced using tomotherapy planning (range: 10-53% reduction, mean: 31%). The volume of lung receiving more than 20 Gy was also reduced in all cases using tomotherapy (range: 17-37% reduction, mean: 22%). For a constant lung NTDmean, it is shown that it should be possible to increase tumor dose to up to 160 Gy in certain patients with tomotherapy. The dose to the spinal cord and esophagus was also reduced in all cases with tomotherapy planning, compared with plans generated using conventional field arrangements. Both tomotherapy, and to a lesser extent conventional three-dimensional conformal radiotherapy, have the potential to significantly decrease radiation dose to lung and other normal structures in the treatment of NSCLC. This has important implications for dose escalation strategies in the future.