Carol Anne Murdoch-Kinch

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

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). METHODS AND MATERIALS A total of 148 HN cancer patients underwent unstimulated and stimulated SMG salivary flow rate measurements selectively from Whartons 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 replanning in 8 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 < or =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 replanning reduced mean contralateral SMG dose by average 12 Gy, achieving < or =39 Gy in 5 of 8 patients, without target underdosing, 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 underdosing is feasible in some patients, at the expense of modestly higher doses to some other organs.

Reducing Xerostomia After Chemo-IMRT for Head-and-Neck Cancer: Beyond Sparing the Parotid Glands

PURPOSE To assess whether, in addition to sparing the parotid glands (PGs), xerostomia after chemotherapy plus intensity-modulated radiotherapy (chemo-IMRT) for head-and-neck cancer is affected by reducing the dose to the other salivary glands. PATIENTS AND METHODS In a prospective study, 78 patients with Stage III-IV oropharynx/nasopharynx cancer underwent chemo-IMRT, with the aim of sparing the parts of the bilateral PGs, oral cavity (OC) containing the minor salivary glands, and contralateral submandibular gland (SMG) outside the target (when contralateral level I was not a target). Before therapy and periodically for 24 months, validated patient-reported xerostomia questionnaire (XQ) scores and observer-graded xerostomia scores were recorded. Also, the stimulated and unstimulated saliva was measured selectively from each of the PGs and SMGs. The mean OC doses served as surrogates of minor salivary gland dysfunction. Regression models assessed the XQ and observer-graded xerostomia predictors. RESULTS Statistically significant predictors of the XQ score on univariate analysis included the OC, PG, and SMG mean doses and the baseline XQ score, time since RT, and both stimulated and unstimulated PG saliva flow rates. Similar factors were statistically significant predictors of observer-graded xerostomia. The OC, PG, and SMG mean doses were moderately intercorrelated (r = 0.47-0.55). On multivariate analyses, after adjusting for the PG and SMG doses, the OC mean dose (p < .0001), interval from RT (p < .0001), and stimulated PG saliva (p < .0025) were significant predictors of the XQ scores and the OC mean dose and time for observer-graded xerostomia. Although scatter plots showed no thresholds, an OC mean dose of <40 Gy and contralateral SMG mean dose of <50 Gy were each associated with low patient-reported and observer-rated xerostomia at almost all post-therapy points. CONCLUSION The PG, SMG, and OC mean doses were significant predictors of both patient-reported and observer-rated xerostomia after chemo-IMRT, with OC doses remaining significant after adjusting for the PG and SMG doses. These results support efforts to spare all the salivary glands by IMRT, beyond the PGs alone.

Recovery of salivary epidermal growth factor in parotid saliva following parotid sparing radiation therapy: a proof-of-principle study

BACKGROUND Although radiation therapy (RT) causes permanent xerostomia, parotid-sparing radiation therapy (PSRT) ensures recovery of saliva quantity over time. Salivary epidermal growth factor (EGF) is produced primarily by parotid glands. OBJECTIVES The aim of this study was to determine whether salivary EGF can be detected in parotid saliva after PSRT and whether protein secretion is time dependent. STUDY DESIGN Salivary EGF concentration (pg/mL) was determined by enzyme-linked immunosorbent assay in stimulated parotid saliva before RT and at 3, 6, and 12 months after RT from 22 patients with head and neck cancer treated with PSRT. RESULTS Saliva samples were from 17 men and 5 women (age ranges 23-70 years and 46-71 years, respectively). At 6 months after RT, EGF concentration was 407 pg/mL lower than at baseline (P = .045). Twelve months after PSRT, parotid glands produce substantial amounts of EGF and other proteins, eventually approximating pre-RT levels, with recovery of salivary function. CONCLUSIONS This proof-of-principle study shows that even proteins in picogram quantities, such as EGF, can be detected in saliva after PSRT.