Dose-Effect Relationships for the Submandibular Salivary Glands and Implications for Their Sparing by Intensity Modulated Radiotherapy

Abstract

Purpose-Submandibular salivary glands (SMGs) dysfunction contributes to xerostomia after radiotherapy (RT) of head and neck (HN) cancer. We assessed SMG dose-response relationships and their implications for sparing these glands by intensity modulated radiotherapy (IMRT).Patients and Methods-148 HN cancer patients underwent unstimulated and stimulated SMG salivary flow rate measurements selectively from Wharton's duct orifices, before RT and periodically through 24 months after RT. Correlations of flow rates and mean SMG doses were modeled throughout all time points. IMRT re-planning in eight patients whose contralateral level I was not a target incorporated the results in a new cost function aiming to spare contralateral SMGs.Results-Stimulated SMG flow rates decreased exponentially by (1.2%) Gy as mean doses increased up to 39 Gy threshold, and then plateaued near zero. At mean doses ≤39 Gy, but not higher, flow rates recovered over time at 2.2%/month. Similarly, the unstimulated salivary flow rates decreased exponentially by (3%) Gy as mean dose increased and recovered over time if mean dose was <39 Gy. IMRT re-planning reduced mean contralateral SMG dose by average 12 Gy, achieving ≤39 Gy in 5/8 patients, without target under-dosing, increasing the mean doses to the parotid glands and swallowing structures by average 2-3 Gy.Conclusions-SMG salivary flow rates depended on mean dose with recovery over time up to a threshold of 39 Gy. Substantial SMG dose reduction to below this threshold and without target under-dosing is feasible in some patients, at the expense of modestly higher doses to some other organs.

Early clinical experience with volumetric modulated arc therapy in head and neck cancer patients

“…On the toxicity side, besides the attention given to spinal cord and brain stem (with toxicity thresholds of 45-50 Gy for the first and at 50 Gy for the second in most of the investigations), it is consolidated knowledge that, for parotids, mean doses inferior to [25][26][27][28][29][30] Gy correlate well with substantial recovery of function within two years (Li et al (4), Deasy et al (5)). Higher thresholds were observed for sub-mandibular glands in the range of 39 Gy by Murdoc et al (6), while a dose to oral cavity of about 30Gy for late mucositis was reported by Narayan et al (7). Recently, the wide application of IMRT allowed also investigations on strategies to reduce other common toxicity patterns.…”

Submandibular gland sparing in intensity-modulated radiotherapy for N0-stage nasopharyngeal carcinoma

“…A mean dose (D mean ) of 39 Gy is the highest threshold dose reported to date. 6 The salivary flow was significantly reduced when the mean dose to the SMG was .39 Gy. Therefore, in this study, we set the restricted mean dose to the SMG at 39 Gy.…”

“…Taking the result of Murdoch-Kinch et al 6 as a reference, a limitation of D mean #39 Gy was added to SMGs in plans B, C and D, but the dose to PTVnx and PTV1 took priority over the limitation to SMGs. In addition, at least 95% of PTV-IIa in plan C and 90% of PTV-IIa in plan D had to have a 60 Gy covering.…”

“…Preservation of SMG function was reported for head and neck cancer treated with IMRT. [5][6][7] However, data from our institution showed that the average unplanned dose received by SMGs was 58 Gy in IMRT of N0-stage NPC, although level I neck nodes were omitted for selected irradiations.…”

“…[5][6][7] However, is it possible to spare the bilateral SMGs in N0-stage NPC patients but what will be the subsequent trade-off of dose distribution to planning target volume 1 (PTV1) around the SMG area? This study was designed to address this question, and the results will be a valuable reference in planning the IMRT of NPC.…”