Increase in mast cells and hyaluronic acid correlates to radiation-induced damage and loss of serous acinar cells in salivary glands: the parotid and submandibular glands differ in radiation sensitivity.

The detailed mechanisms which can explain the inherent radiosensitivity of salivary glands remain to be elucidated. Although DNA is the most plausible critical target for the lethal effects of irradiation, interactions with other constituents, such as cell membrane and neuropeptides, have been suggested to cause important physiological changes. Moreover, mast cells seem to be closely linked to radiation-induced pneumonitis. Therefore, in the present study the effects of fractionated irradiation on salivary glands have been assessed with special regard to the appearance of mast cells and its correlation with damage to gland parenchyma. Sprague-Dawley strain rats were unilaterally irradiated to the head and neck with the salivary glands within the radiation field. The irradiation was delivered once daily for 5 days to a total dose of 20, 35 and 45 Gy. The contralateral parotid and submandibular glands served as intra-animal controls and parallel analysis of glands was performed 2, 4, 10 or 180 days following the last radiation treatment. Morphological analysis revealed no obvious changes up to 10 days after the irradiation. At 180 days a radiation dose-dependent loss of gland parenchyma was seen, especially with regard to serious acinar cells in parotid gland and acinar cells and serous CGT (convoluted granular tubule) cells in the submandibular gland. These changes displayed a close correlation with a concomitant dose-dependent enhanced density of mast cells and staining for hyaluronic acid. This cell population seems to conform with the features of the connective tissue mast cell type. The parotid seems to be more sensitive to irradiation than the submandibular gland. Thus, the present results further strengthen the role of and the potential interaction of mast cells with radiation-induced tissue injury and alterations in normal tissue integrity.     

Volume effects and region-dependent radiosensitivity of the parotid gland

PURPOSE: To detect volume effects and possible regional differences in radiosensitivity of the rat parotid gland. METHODS AND MATERIALS: Parotid glands of male albino Wistar rats were locally X-irradiated, with collimators with conformal radiation portals used to supply 100% volume and 50% cranial/caudal partial volumes. High-resolution magnetic resonance imaging was used to provide the outlines of the parotid glands. Single doses of up to 40 Gy were applied, and the effects on saliva secretion, measured with the aid of miniaturized Lashley cups, were followed up to 365 days after the irradiation. RESULTS: Under conditions of equal mean absorbed doses and small variations in dose distribution, a pertinent volume effect was observed for late but not for early radiation damage. The late effects were different for the cranial part as compared with the caudal part of the parotid gland. The reduction in flow rate was much more severe after irradiation in the cranial part. After a single dose of 30 Gy, the reductions in flow rates were approximately 65% and 25% for the cranial and caudal parts, respectively. At that dose, no saliva flow was observed after irradiation of 100% of the gland. CONCLUSION: From the rat model studies presented, it is concluded that late radiation damage after partial irradiation of parotid glands shows region-dependent volume effects. This finding is expected to be relevant to the radiosensitivity of human salivary glands, and it implies that the predictive power of the mean dose concept in radiotherapeutic practice is limited. The finding of region-dependent late radiation damage also challenges the basic assumptions of most current normal tissue complication probability models for parotid gland function.     

Target cell and mode of radiation injury in rhesus salivary glands

Morphological alterations of parotid and submandibular salivary glands of rhesus monkeys were studied 1-72 h and 16-40 weeks postirradiation (PI) with single photon doses of 2.5-15.0 Gy, or 10.2 Gy given in 6 fractions. Acute degeneration and necrosis of serous cells in both parotid and submandibular glands were clearly expressed by 24 h PI and occurred in a dose-related fashion. In submandibular glands, doses of 12.5 or 15.0 Gy damaged mucous cells, but to a considerably lesser extent than the serous cells in the same glands. No significant sparing was evident with dose fractionation. These observations demonstrate the unique sensitivity of serous cells which appear to undergo interphase cell death after irradiation. The results also show that late atrophy was the direct result of acute loss of serous acini and reflects a lack of regeneration of acinar cells receiving acute injury.     

鼻咽癌面颈联合野放疗对唾液腺功能影响的临床分析

目的 :利用放射性核素99mTcO4-动态显像唾液腺定量测定鼻咽癌面颈联合野放疗前、中、后唾液腺功能的变化并探讨与放疗剂量之间的关系。方法 :2 0 0 3年 2月 1日～ 2 0 0 3年 10月 3 1日 ,分别对 2 0例鼻咽癌面颈联合野放疗患者于放疗前、放疗至 10、3 6～ 40、70Gy时进行99mTcO4-动态显像定量测定其唾液腺(腮腺、颌下腺 )摄锝率 (UR)、泌锝率 (ER)变化 ,同时观察其口干程度进行临床分级。结果 :2 0例鼻咽癌面颈联合野放疗剂量为 10和3 6～ 40Gy时 ,其泌锝率明显低于放疗前 ,P <0 0 5 ,在放疗 70Gy时降到最低 ,P <0 0 1。与临床观察到的口干严重程度一致 ,而其摄锝率在 3 6～ 40Gy照射以前变化不明显 ,无统计学意义。结论 :鼻咽癌面颈联合野照射患者放疗前无明显唾液腺功能障碍 ,随着放疗剂量的增加 ,唾液腺功能明显下降 ,其ER较UR下降明显 ,在确保患者放疗疗效的同时 ,应尽可能提高放疗技术 ,减少唾液腺照射剂量和放疗体积 ,保护唾液腺功能 ,以提高患者的生活质量。     

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.     

Diffusion-weighted magnetic resonance imaging to evaluate major salivary gland function before and after radiotherapy

PURPOSE: To evaluate diffusion-weighted (DW)-MRI as a noninvasive tool to investigate major salivary gland function before and after radiotherapy (RT) for head and neck cancer (HNC). METHODS AND MATERIALS: DW-MRI was performed in 8 HNC patients before and after parotid-sparing RT (mean dose to the contralateral parotid gland <26 Gy). A DW sequence was performed once at rest and then repeated continuously during salivary stimulation. Apparent diffusion coefficient (ADC) maps for both parotid and submandibular glands were calculated. Findings were compared with salivary gland scintigraphy. RESULTS: Before RT, the mean ADC value at rest was significantly lower in the parotid than in the submandibular glands. During the first 5 min of stimulation, the ADC value of the salivary glands showed a decrease, followed by a steady increase until a peak ADC, significantly higher than the baseline value, was reached after a median of 17 min. The baseline ADC value at rest was significantly higher after RT than before RT in the nonspared salivary glands but not in the spared parotid glands. In the contralateral parotid glands, the same response was seen as before RT. This pattern was completely lost in the nonspared glands. These results corresponded with remaining or loss of salivary function, respectively, as confirmed by salivary gland scintigraphy. CONCLUSIONS: Diffusion-weighted-MRI allows noninvasive evaluation of functional changes in the major salivary glands after RT and is a promising tool for investigating radiation-induced xerostomia.     

11C-methionine PET, a novel method for measuring regional salivary gland function after radiotherapy of head and neck cancer.

BACKGROUND AND PURPOSE: Loss of salivary gland function is a distressing side-effect of radiotherapy (RT) for head and neck cancer. The aim of this study was to develop a positron emission tomography (PET) method for measuring regional salivary gland function in the major salivary glands irradiated during RT. PATIENTS AND METHODS: Eight head and neck cancer patients were included; two were examined before RT and six after parotid sparing RT. Patients were examined by dynamic 11C-methionine PET of the major salivary glands and parotid gland salivary flow measurements. PET data were analysed using a kinetic model of salivary gland 11C-methionine metabolism, in which salivary gland function was quantified by the net metabolic clearance of 11C-methionine, K. Functional voxel-wise images of K were calculated and matched with the CT-dose-plan for comparing regional salivary gland function with the regional radiation dose. RESULTS: Parotid gland K correlated positively with parotid gland salivary flow, indicating that K can be used as an index of salivary gland function. K of parotid and submandibular glands was reduced dependent on the median radiation dose. In one patient, receiving a heterogeneous radiation dose to the parotid glands, regional salivary gland function was inversely correlated to the regional radiation dose. CONCLUSIONS: Salivary gland function can be measured by dynamic 11C-methionine PET. The net metabolic clearance of 11C-methionine of salivary glands was reduced dependent on the radiation dose. Dynamic 11C-methionine PET offers a method for studying the individual response of the major salivary glands to irradiation.     

Beam intensity modulation using tissue compensators or dynamic multileaf collimation in three-dimensional conformal radiotherapy of primary cancers of the oropharynx and larynx, including the elective neck

Introduction: The treatment of midline tumors in the head and neck by conventional radiotherapy almost invariably results in xerostomia. This study analyzes whether a simple three-dimensional conformal radiotherapy (3D-CRT) technique with beam intensity modulation (BIM) (using a 10-MV beam of the MM50 Racetrack Microtron) can spare parotid and submandibular glands without compromising the dose distribution in the planning target volume (PTV).

Methods: For 15 T2 tumors of the tonsillar fossa with extension into the soft palate (To) and 15 T3 tumors of the supraglottic larynx (SgL), conventional treatment plans, consisting of lateral parallel opposed beams, were used for irradiation of both the primary tumor (70 Gy) and the elective neck regions (46 Gy). Separately, for each tumor a 3-D conformal treatment plan was developed using the 3-D computer planning system, CadPlan, and Optimize, a noncommercial program to compute optimal beam profiles. Beam angles were selected with the intention of optimal sparing of the salivary glands. The intensity of the beams was then modulated to achieve a homogeneous dose distribution in the target for the given 3D-CRT techniques. The dose distributions, dose–volume histograms (DVHs) of target and salivary glands, tumor control probabilities (TCPs), salivary gland volumes absorbing a biologically equivalent dose of greater than 40 or 50 Gy, and normal tissue complication probabilities (NTCPs) of each treatment plan were computed. The parameters of the 3D-CRT plans were compared with those of the conventional plans.

Results: In comparison with the conventional technique, the dose homogeneity in the target volume was improved by the conformal technique for both tumor sites. In addition, for the SgL conformal technique, the average volumes of the parotid glands absorbing a BED of greater than 40 Gy (V40) decreased by 23%, and of the submandibular glands by 7% (V40) and 6% (V50). Consequently, the average NTCPs for the parotid and submandibular glands were reduced by 7% and 6%, respectively. For the To conformal techniques, the V40 of the parotid glands was decreased on average by 31%, resulting in an average reduction of the NTCP by 49%. Both the average V50 and the NTCP of the submandibular glands were decreased by 7%.

Conclusion: For primary tumors of the oropharynx, the parotid glands could be spared to a considerable degree with the 3D-CRT technique. However, particularly the ipsilateral submandibular gland could not be spared. For primary tumors of the larynx, the 3D-CRT technique allows sparing of all salivary glands to a considerable and probably clinically relevant degree. Moreover, the conformal techniques resulted in an increased dose homogeneity in the PTV of both tumor sites.     

On the mechanism of salivary gland radiosensitivity

PURPOSE: To contribute to the understanding of the enigmatic radiosensitivity of the salivary glands by analysis of appropriate literature, especially with respect to mechanisms of action of early radiation damage, and to supply information on the possibilities of amelioration of radiation damage to the salivary glands after radiotherapy of head-and-neck cancer. METHODS AND MATERIALS: Selected published data on the mechanism of salivary gland radiosensitivity and radioprotection were studied and analyzed. RESULTS: From a classical point of view, the salivary glands should not respond as rapidly to radiation as they appear to do. Next to the suggestion of massive apoptosis, the leakage of granules and subsequent lysis of acinar cells was suggested to be responsible for the acute radiation-induced function loss of the salivary glands. The main problem with these hypotheses is that recently performed assays show no cell loss during the first days after irradiation, while saliva flow is dramatically diminished. The water secretion is selectively hampered during the first days after single-dose irradiation. Literature is discussed that shows that the compromised cells suffer selective radiation damage to the plasma membrane, disturbing signal transduction primarily affecting watery secretion. Although the cellular composition of the submandibular gland and the parotid gland are different, the damage response is very alike. The acute radiation-induced function loss in both salivary glands can be ameliorated by prophylactic treatment with specific receptor agonists. CONCLUSIONS: The most probable mechanism of action, explaining the enigmatic high radiosensitivity for early effects, is selective radiation damage to the plasma membrane of the secretory cells, disturbing muscarinic receptor stimulated watery secretion. Later damage is mainly due to classical mitotic cell death of progenitor cells, leading to a hampered replacement capacity of the gland for secretory cells, but is also caused by damage to the extracellular environment, preventing proper cell functioning.     

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.     

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.     

鼻咽癌适形调强放疗中涎腺功能的全面保护

  目的  探讨鼻咽癌适形调强放疗(intensity modulate radiation therapy, IMRT)患者各涎腺功能的保护方法。  方法  选取2010年3月至2012年11月101例连续于中山大学肿瘤医院接受IMRT鼻咽癌患者, 勾画危及器官, 包括腮腺、颌下腺、口腔, 于3、6、12、18、24个月复查时采用面对面访谈式问卷调查评分口干程度情况, 并结合剂量体积直方图(dose-volume histograms, DVH)进行分析。  结果  腮腺平均剂量(MD)为37.4 Gy (患侧), 33.8 Gy (健侧); 颌下腺MD为51.6 Gy (患侧), 45.7 Gy (健侧); 口腔MD为38.2 Gy。77.2%(78/101)患者放疗结束后6个月口干症状明显改善, 1年后中度(G3)以上口干患者 < 5.0%(5/101)。  结论  随着时间的推移, 放疗后口干燥症明显改善; 限定至少一侧腮腺V30~35≤50.0%, 至少一侧颌下腺V40~45≤66.7%~50.0%, 口腔MD < 40 Gy可有效保护唾液腺功能。      

Dose-response relationships within the parotid gland after radiotherapy for head and neck cancer.

BACKGROUND AND PURPOSE: To determine the salivary function, after parotid-sparing radiotherapy (RT), of different regions within the parotid gland and to evaluate dose-function relationships within the parotid glands and between patients. PATIENTS AND METHODS: Sixteen head and neck cancer patients, irradiated between September 1999 and November 2000 using a conformal parotid-sparing technique, were included in this study. Before RT and 7 months after RT (range 6-10 months), a salivary gland scintigraphy was performed in all patients combined with a single photon emission computed tomography (SPECT). The salivary excretion fraction (SEF) was measured, after stimulation, in 8-12 transverse 5mm SPECT slices of each parotid. Loss of salivary excretion fraction (dSEF %) of these slices was calculated as the proportion of SEF after RT as compared to SEF before RT. Since the planning CT-scan and the SPECT-scintigraphy were performed in the same treatment position, the dose to a transverse slice within the parotid gland could be matched to the loss of salivary excretion fraction of that respective slice. A non-linear model was fitted to the dose-loss of function data and the dose resulting in 50% loss of salivary excretion fraction (D50) was calculated. RESULTS: Before RT, all but one patient presented with normal salivary excretion fractions (SEF) of both parotid glands. Within the same parotid gland, the SEF's of the different slices were almost equal. Seven months after RT, the reduction in SEF was statistically significant (P-value<0.0001). A significant difference in loss of salivary excretion fraction (dSEF) was also observed between both parotid glands (P<0.0001) as a result of the parotid-sparing technique. When plotting the dSEF of a slice versus the dose given to that slice, doses as low as 10-15 Gy could result in a serious loss of function (dSEF>50%). After fitting a non-linear model to these plots, the mean dose resulting in 50% loss of salivary excretion fraction (D50) 7 months after RT was 22.5 Gy. A large inter-patient variability was found in D50. CONCLUSIONS: Salivary SPECT is a useful tool for the evaluation of the salivary function of different slices within the parotid gland. Before irradiation, the different slices within one parotid gland act as functional sub-units contributing equally to the function of the entire gland. Seven months after an average dose of 22.5 Gy (D50) the functional sub-unit has lost 50% of its excretion fraction. The high inter-patient variability in D50 and the observation that low doses (10-15 Gy) can induce serious loss of function should prompt us in the clinic to reduce the dose to the parotids even lower than the threshold of 22.5 Gy.     

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.     

Equivalence of hyperfractionated and continuous brachytherapy in a rat tumor model and remarkable effectiveness when preceded by external irradiation

Purpose: In clinical brachytherapy, there is a tendency to replace continuous low-dose-rate (LDR) irradiation by either single-dose or fractionated high-dose-rate (HDR) irradiation. In this study, the equivalence of LDR treatments and fractionated HDR (2 fractions/day) or pulsed-dose-rate (PDR, 4 fractions/day) schedules in terms of tumor cure was investigated in an experimental tumor model.

Methods and Materials: Tumors (rat rhabdomyosarcoma R1M) were grown s.c. in the flank of rats and implanted with 4 catheters guided by a template. All interstitial radiation treatment (IRT) schedules were given in the same geometry. HDR was given using an ¹⁹²Ir single-stepping source. To investigate small fraction sizes, part of the fractionated HDR and PDR schedules were applied after an external irradiation (ERT) top-up dose. The endpoint was the probability of tumor control at 150 days after treatment. Cell survival was estimated by excision assay.

Results: Although there was no fractionation effect for fractionated HDR given in 1 or 2 fractions per day, TCD₅₀-values were substantially lower than that for LDR. A PDR schedule with an interfraction interval of 3 h (4 fractions/day), however, was equivalent to LDR. The combination of ERT and IRT resulted in a remarkably increased tumor control probability in all top-up regimens, but no difference was found beteeen 2 or 4 fractions/day. Catheter implantation alone decreased the TCD₅₀ for single-dose ERT already by 17.4 Gy. Cell viability assessed at 24 h after treatment demonstrated an increased effectiveness of interstitial treatment, but, after 10 Gy ERT followed by 10 Gy IRT (24-h interval), it was not less than that calculated for the combined effect of these treatments given separately.

Conclusion: In full fractionation schedules employing large fractions and long intervals, the sparing effect of sublethal damage repair may be significantly counteracted by reoxygenation. During 3-h intervals, however, repair may be largely completed with only partial reoxygenation causing PDR schedules to be less effective than fractionated HDR, and equivalent to LDR. Brachytherapy with clinically sized fractions after a large external top-up dose showed a remarkable increase in tumor control rate with no effect of fractionation (up to 4 fractions/day), which could not be fully explained by differences in dose distribution or in the cell viabilily assessed after treatment. This suggests a longer lasting effect on cell survival or radiosensitivity associated with catheter implantation shortly after the top-up dose.     

Optimum dose range for the amelioration of long term radiation-induced hyposalivation using prophylactic pilocarpine treatment.

BACKGROUND: To determine dose and time dependency of pilocarpine pre-treatment protection from late damage after unilateral irradiation of the rat parotid gland. METHODS AND MATERIALS: The right parotid gland of saline (1mg/ml) or pilocarpine (4 mg/kg) pre-treated rats was irradiated with 10, 15 and 20 Gy. Saliva was collected from the irradiated and shielded parotid before, 30, 60, 120 and 240 days after irradiation. The number of acinar cells/gland was determined 30, 120 and 240 days after irradiation by histological examination. RESULTS: Pilocarpine pre-treated rats, protection of parotid gland function was seen in the early-intermediate phase (0-120 days) after 15 Gy and in the late phase (>120 days) after 10 and 15 Gy. Although no protection was observed after 20 Gy, a stimulatory effect of pilocarpine on the non-irradiated gland resulted in a significant increase in total saliva secretion. The increase in function after pilocarpine treatment was paralleled by a significant increase in the number of acinar cells in both the irradiated and shielded glands. CONCLUSIONS: Pre-irradiation treatment with pilocarpine induces compensatory response, at lower doses, in the irradiated and at higher doses in the non-irradiated gland reducing late damage, due to stimulation of unirradiated or surviving cells to divide.     

Parotid and submandibular/sublingual salivary flow during high dose radiotherapy.

It was studied whether differences in acute radiosensitivity exist between parotid and submandibular/sublingual glands. The results revealed that salivary flow rates decreased dramatically during the first 2 weeks of radiotherapy. Neither recovery nor significant differences were observed between the production of saliva from the parotid and submandibular/sublingual glands during the 13 weeks observation period.     

Plasma Amylase Activity as a Biochemical Indicator of Radiation Injury to Salivary Glands

Irradiation of the salivary glands produces a rapid increase of salivary amylase in serum, released by the highly radiation sensitive serous cells of the glands. Serial assays of salivary amylase in serum were performed in patients treated by radiation to the upper neck region. The changes observed were compared with the amount of salivary gland mass irradiated and with the dose fractionation modality used. The irradiated volume included either the entire salivary gland mass or less than 50 per cent of the gland. Two fractionation modalities were used: a conventional fractionation of 2 Gy per day, 5 times a week, or a multiple daily fractionation of 2 Gy, 3 times a day in two series of 4 days with a 4-day interval. Both parameters (salivary gland mass irradiated and fractionation modality used) significantly influenced the shape of the amylase curve in the serum. Serum amylase may therefore be considered a reliable biologic indicator of early injury to the salivary glands.     

磁共振涎管成像评价早期鼻咽癌放疗前后涎腺影像变化与口干关系初探

目的 探索磁共振涎管成像(MRS)评价鼻咽癌放疗前后涎腺影像变化的可行性,及其与患者主观评价的相关性.方法 放疗前、后患者分别行MRS,应用MRS评分系统对患者放疗前、后酸刺激前后涎腺导管进行评分,并结合美国放疗肿瘤组织急性放射损伤标准和欧洲癌症研究与治疗组织QLQ-C30v3.0和QLQ-H&N35量表进行分析.结果 共10例患者进入研究.所有患者双侧腮腺平均受照剂量为(37.99 ±3.70) Gy,双侧颌下腺平均受照剂量为(55.65±2.99) Gy.MRS图像显示酸刺激使涎腺导管评分升高,放疗后导管评分下降,对酸刺激反应较放疗前差.放疗后酸刺激前后腮腺导管评分差值与QLQ-C30量表的总生活质量领域得分呈正相关性(rs=0.636,P=0.048),与QLQ-H&N35量表中的口干条目得分呈负相关性(rs=-0.694,P=0.026).结论 MRS可无创检测涎腺放疗前后影像变化,用来评价鼻咽癌患者放疗后早期口干严重程度有一定的临床参考价值.     

颌下腺移位术预防放疗后口干燥症的动物实验模型

目的：通过建立兔颌下腺移位的动物实验模型,探讨兔颌下腺移位术的可行性。方法：实验组：7只新西兰兔均将左侧颌下腺移位至颏下区。术后接受不同剂量（2～14Gy）的电离辐射,移位侧的颌下腺在照射野之外。对照组：7只新西兰兔将左侧颌下腺移位至颏下区,术后不接受电离辐射。20周时将移位侧及未移位侧的颌下腺游离之后全部取出,观察其病理变化。结果：实验组未移位侧颌下腺组织病理变化：在照射后20周时,照射剂量6、8Gy的颌下腺组织中腺泡细胞间隙增宽、腺泡明显萎缩、腺泡数目明显减少,间质纤维组织增生、增厚;照射剂量10、12、14Gy的颌下腺组织腺泡的间隙明显增宽。实验组和对照组移位侧颌下腺组织病理变化与正常颌下腺的组织学形态无差异。结论：颌下腺移位术通过将颌下腺移位至颏下区,避免了直接照射,成功地保护了移位的颌下腺。