Scintigraphy in prediction of the salivary gland function after gland-sparing intensity modulated radiation therapy for head and neck cancer

BACKGROUND AND PURPOSE: To evaluate salivary gland scintigraphy in prediction of salivary flow following radiation therapy. PATIENTS AND METHODS: Twenty patients diagnosed with head and neck cancer were treated with intensity modulated radiation therapy with an intention to spare the salivary gland function. The total quantitative saliva secretion was measured prior to and 6 and 12 months after therapy, and the function of the major salivary glands was monitored using Tc-99m-pertechnetate scintigraphy. Two models were designed for prediction of the post-treatment salivary flow: an average model, based on the average proportions of saliva produced by each of the four major glands in healthy subjects, and an individual model, based on saliva produced by each gland as measured by scintigraphy prior to therapy. These models were compared with volume-based (Lyman) normal tissue complication probability models using two published sets of model parameters. RESULTS: The D(50) for the parotid and the submandibular gland function assessed at 6 and 12 months after radiotherapy was approximately 39Gy. The scintigraphy-based individual model predicted well the measured post-treatment saliva flow rates. The correlation coefficient between the predicted stimulated and the measured saliva flow rate was 0.77 (p<0.0001) at 6 months and 0.55 (p=0.034) at 12 months after completion of radiotherapy. The relative changes in unstimulated and stimulated salivary flow rates showed similar dependency on the cumulative radiation dose. CONCLUSIONS: Salivary gland function assessed by scintigraphy prior to radiotherapy is useful in prediction of the residual salivary flow after radiotherapy.     

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.     

The changes in irradiated salivary gland function of patients with head and neck tumors treated with radiotherapy

BACKGROUND: To investigate and analyze changes in irradiated salivary gland function of patients with head and neck tumors treated with radiotherapy. METHODS: Thirty-seven patients with head and neck tumors, who received 40-70 Gy of irradiation to all major salivary glands, were analyzed. The weights of saliva secreted for 10 minutes at rest, and for 5 minutes with vitamin C stimulation, were measured. The salivary gland function was defined by the weight of saliva. RESULTS: With vitamin C stimulation, the weight of saliva in patients whose doses were < or =50 Gy, was significantly higher than that of patients whose doses were > or = 58 Gy (2.48 +/- 0.33 g vs. 0.73 +/- 0.18 g, P = 0.0003). When doses administered to salivary glands were < or =50 Gy, the stimulated saliva secretion recovered over time, after irradiation. However, when the doses of irradiation were > or = 58 Gy, there was no recovery in saliva secretion even after a few years. Multiple regression analysis showed that age and chemotherapy may not affect salivary gland function even years after radiotherapy. CONCLUSION: When salivary glands were irradiated with doses < or =50 Gy, gradual recovery of salivary gland function was observed over time, whereas there was no significant recovery when the irradiation dose was >58 Gy.     

Optimized radiotherapy for head and neck cancer.

Optimization of radiation therapy for head and neck tumors requires the combination of several facets of radiation biology and physics. The aim is to achieve optimum tumor control while reducing normal tissue damage. Techniques have been developed to determine tumor radiosensitivity and growth characteristics. Their use as predictive assays of treatment response is gaining importance. As the range of therapeutic options (particularly altered fractionation regimens) increases, it is hoped that the ability to individually tailor patients' treatment will result in improved rates of tumor control and an improved therapeutic ratio. Optimization of treatment delivery based on three-dimensional treatment planning offers the opportunity for dose escalation studies and limitation of normal tissue morbidity. The combination of chemotherapy and radiotherapy continues to be investigated, although major advances using this strategy are unlikely.     

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.     

Intensity modulated radiotherapy for elderly bladder cancer patients

Background

Radiation therapy plays a central role in the management of many childhood malignancies and Helical Tomotherapy (HT) provides potential to decrease toxicity by limiting the radiation dose to normal structures. The aim of this article was to report preliminary results of our clinical experience with HT in pediatric malignancies.

Methods

In this study 66 consecutive patients younger than 14 years old, treated with HT at our center between January 2006 and April 2010, have been included. We performed statistical analyses to assess the relationship between acute toxicity, graded according to the RTOG criteria, and several clinical and treatment characteristics such as a dose and irradiation volume.

Results

The median age of patients was 5 years. The most common tumor sites were: central nervous system (57%), abdomen (17%) and thorax (6%). The most prevalent histological types were: medulloblastoma (16 patients), neuroblastoma (9 patients) and rhabdomyosarcoma (7 patients). A total of 52 patients were treated for primary disease and 14 patients were treated for recurrent tumors. The majority of the patients (72%) were previously treated with chemotherapy. The median prescribed dose was 51 Gy (range 10-70 Gy). In 81% of cases grade 1 or 2 acute toxicity was observed. There were 11 cases (16,6%) of grade 3 hematological toxicity, two cases of grade 3 skin toxicity and one case of grade 3 emesis. Nine patients (13,6%) had grade 4 hematological toxicity. There were no cases of grade 4 non-hematological toxicities. On the univariate analysis, total dose and craniospinal irradiation (24 cases) were significantly associated with severe toxicity (grade 3 or more), whereas age and chemotherapy were not. On the multivariate analysis, craniospinal irradiation was the only significant independent risk factor for grade 3-4 toxicity.

Conclusion

HT in pediatric population is feasible and safe treatment modality. It is characterized by an acceptable level of acute toxicity that we have seen in this highly selected pediatric patient cohort with clinical features of poor prognosis and/or aggressive therapy needed. Despite of a dosimetrical advantage of HT technique, an exhaustive analysis of long-term follow-up data is needed to assess late toxicity, especially in this potentially sensitive to radiation population.     

Intraoperative radiotherapy for pre-irradiated head and neck cancer.

BACKGROUND AND PURPOSE: Radiotherapy of recurrent head and neck tumours is limited in dose due to pre-treatment up to normal tissue tolerance doses. Surgery alone is limited by the problems related to pre-surgery, post-radiation fibrosis, and infiltration of tumours into nerves and vessels too closely to be completely removed. Our aim was to evaluate the possible role of intraoperative radiotherapy (IORT) in such tumours treated with palliative intent. METHODS: In the last 10 years, we performed 113 intraoperative irradiations in a total of 84 pre-irradiated patients with head and neck cancer. The patient data were evaluated with regard to palliative effect, complications of treatment, recurrence and survival after IORT. RESULTS: Palliation of symptoms, as assessed by clinical evaluation, was achieved in 88% of symptomatic patients, often just by removal of large exophytic or exulcerating tumours, with IORT preventing their immediate recurrence after surgery. The complication rate did not exceed that expected after surgery alone. The median survival after IORT was 6.8 months, with a median time to local tumour recurrence or progression of 3.7 months. CONCLUSION: Intraoperative irradiation can be used as a palliative treatment option in pre-treated head and neck tumours with satisfactory results. With large and infiltrating tumours, however, recurrences or tumour progression occur close to the IORT portals, thus rendering this method unsuitable for achieving long-term control in such extended tumours.     

Modern radiotherapy for head and neck cancer

Radiation therapy (RT) plays a key role in curative-intent treatments for head and neck cancers. Its use is indicated as a sole therapy in early stage tumors or in combination with surgery or concurrent chemotherapy in advanced stages. Recent technologic advances have resulted in both improved oncologic results and expansion of the indications for RT in clinical practice. Despite this, RT administered to the head and neck region is still burdened by a high rate of acute and late side effects. Moreover, about 50% of patients with high-risk disease experience loco-regional recurrence within 3 years of follow-up. Therefore, in recent decades, efforts have been dedicated to optimize the cost/benefit ratio of RT in this subset of patients. The aim of the present review was to highlight modern concepts of RT for head and neck cancers considering both the technological advances that have been achieved and recent knowledge that has informed the biological interaction between radiation and both tumor and healthy tissues.     

头颈部唾液腺腺样囊性癌术后调强放疗预后分析

目的:探讨头颈部唾液腺腺样囊性癌(ACC)的综合治疗模式及预后因素。方法:收集2016—2018年间上海交通大学医学院附属第九人民医院放疗科收治的头颈部唾液腺ACC完成术后放疗患者资料进行回顾性分析。 Kaplan- Meier法生存分析, log- rank检验单因素预...     

Intensity‐modulated radiotherapy: Examples of its utility in head and neck cancer

Intensity‐modulated radiotherapy (IMRT) has been available at Peter MaCallum Cancer Centre (PMCC) since November 2000. The present report illustrates two cases of our early experience with IMRT. Case 1 is a 66‐year‐old man with a T₁N₂M₀ nasopharyngeal carcinoma treated with chemo‐radiotherapy using parotid‐sparing IMRT. Fourteen months following treatment he remains in complete remission, with salivary function assessed using a xerostomia‐specific quality of life questionnaire, having returned to near pretreatment levels by 12 months. Case 2 is a 70‐year‐old man with a T₄N₀M₀ base of tongue squamous cell carcinoma treated with chemo‐radiotherapy after refusing radical surgery. He had received subtotal nodal irradiation to 36 Gy in 1994 for Hodgkins disease stage IIA. A radical dose was still achievable despite previous irradiation without exceeding unacceptable spinal cord dose with IMRT. He remains in complete remission 14 months from his initial presentation without evidence of neurological toxicity. Intensity‐modulated radiotherapy allows sparing of critical normal structures in the head and neck without compromising dose to the tumour. It is, therefore, desirable for several clinical applications and essential in some, if unacceptable compromises are not to be made.     

Effects of radiotherapy on parotid salivary sialochemistry in head and neck cancer patients

Aim

To determine the effects of high dose irradiation on parotid salivary sodium and pH concentration at subsequent duration of 1.5, 3 and 6 months following radiotherapy.

Materials and methods

Eighty parotid glands of head and neck cancer patients were irradiated with mean dose of 66 Gy. The stimulated parotid flow (PF) was collected by a cannulation of Stenson’s duct followed by analysis of sodium (PF sodium) by Easylyte Sodium/Potassium auto analyzer and pH by litmus narrow band pH paper.

Results

A steep elevation of PF sodium was found in post-RT period after 1.5 months of starting RT followed by gradual increase up to 6 months and pH changed towards acidity.

Conclusions

A high dose of 66 Gy causes irreversible damage to parotid salivary duct system.     

Changes in serum and salivary amylase during radiotherapy for head and neck cancer: a comparison of conventionally fractionated radiotherapy with CHART.

The changes in serum amylase that occur when radiotherapy is given in the treatment of head and neck cancer has been studied in 41 patients, 29 treated by CHART and 12 by conventionally fractionated radiotherapy. The peak rise in serum amylase following the start of treatment is seen earlier and is greater in the patients receiving continuous hyperfractionated accelerated radiotherapy (CHART). The serum amylase returns to normal earlier in the CHART patients so that the area under the curve is the same for both groups. The difference probably reflects the more rapid delivery of treatment to the patients receiving CHART. A close correlation between the peak rise in serum amylase and the amount of parotid tissue in the treatment volume is demonstrated. For six patients the total amount of amylase secreted by the parotid gland during CHART was measured and found to decline rapidly within a few days of the start of radiotherapy. The rise in serum amylase that results from the irradiation of salivary tissue provides a unique biochemical measure of an early radiation effect in a normal tissue. This probably reflects the interphase cell death of serous salivary cells. Although these immediate changes are of considerable interest they may not relate to the late effects of radiation on salivary gland function.     

Intensity modulated photon and proton therapy for the treatment of head and neck tumors.

PURPOSE: A comparative treatment planning study has been performed between intensity modulated photon and proton therapy to investigate the ability of both modalities to spare organs at risk in the head and neck region while keeping target dose homogeneous. Additional advantage of reducing the spot size for IMPT was also investigated. The treatment planning comparison was extended by varying the number of fields to study its effect on the performance of each modality. Risks of secondary cancer induction were also calculated for all modalities. MATERIALS AND METHODS: Five planning CTs were selected for the study. Four different constraints were set to the organs at risk in order to measure the resulting dose homogeneity in the target volume. Five and nine field plans were made for IMXT and 3, 5 and 9 field plans were made for IMPT, for both spot sizes. Dose homogeneity as a function of the mean parotid dose was visualized using a 'pseudo' Pareto-optimal front approach. Risks of secondary cancer were estimated using the organ equivalent dose model. RESULTS: Critical organs were best spared using 3-field IMPT and, at least for IMPT, little advantage was seen with increasing field numbers. Reducing the spot size does give an advantage. In contrast, there was a significant advantage in going from 5 to 9 fields for IMXT. Secondary cancer risk was lowest for the IMPT plans with reduced spot size, for which normal tissue received the lowest integral dose. Interestingly, although integral dose remained the same, increasing the number of IMPT fields increased the secondary cancer risk, due to the increased volume of tissue irradiated to low dose. CONCLUSIONS: IMPT has a better ability to spare organs at risk than IMXT for the same dose homogeneity. It also significantly reduced the estimated risk of secondary cancer induction and the use of small numbers of fields further increased this advantage. Given that target homogeneity and normal tissue sparing were equally good with the 3 field IMPT, there appears to be a clear rationale to deliver small numbers of fields for IMPT.     

Maintained salivary function after brachytherapy in patients with head and neck carcinomas--evaluation using quantitative salivary gland scintigraphy

The purpose of this study was to determine whether or not salivary gland dysfunction occurs within the first three months after brachytherapy in patients with head and neck carcinoma. Of the 20 patients with head and neck squamous cell carcinoma included in this study, 11 were treated with brachytherapy and the remaining 9 patients received external irradiation. All the patients underwent a salivary gland scintigraphy before and after radiotherapy. The scintigraphic parameters of each major salivary gland were then compared before and after the radiotherapy. In the brachytherapy group, none of the scintigraphic functional parameters showed a significant change before and after the radiotherapy. In contrast, all of the parameters with the exception of the uptake ratio (UR) of the submandibular glands significantly decreased after external irradiation. This observation was to be expected owing to the different irradiation doses administered by the two techniques. The scintigraphic technique used to evaluate salivary gland function should be used in future intensity-modulated radiation therapy salivary-gland-sparing studies in order to evaluate both the acute and chronic effects of irradiation in head and neck cancer patients.     

Recurrences after conformal parotid-sparing radiotherapy for head and neck cancer.

BACKGROUND AND PURPOSE: Evaluation of loco-regional failure patterns and survival after parotid-sparing three-dimensional conformal and intensity modulated radiotherapy (IMRT) for head and neck cancer. PATIENTS AND METHODS: From June 1999 to July 2002, seventy-two patients with lateralised head and neck tumours, excluding nasopharyngeal tumours and patients with bilateral or contralateral neck disease, were irradiated with a parotid-sparing technique. Three-dimensional conformal planning was used in 68 patients, 4 patients were treated with dynamic IMRT. Bilateral neck node irradiation was performed in all patients, the junctional (or high level II) nodes, contralateral to the tumour, however, were excluded from the clinical target volume to spare the adjacent parotid from irradiation. In 20 patients with persistent or recurrent loco-regional disease, the localisation and volume of the treatment failure, as determined by computed tomography (CT), was copied on the pre-treatment CT-study used for treatment planning. Minimum, mean and maximum doses administered to the region of the failure were calculated and dose--volume histograms were computed of each failure. The failures were divided in three groups depending on the percentage of their volume receiving 95% of the prescribed dose. Recurrences were defined to be in-field (IF) if >95% of their volume received 95% of the prescribed dose and out-field (OF) if <20% of their volume received 95% of the prescribed dose. When 20-95% of the volume of the recurrence received 95% of the prescribed dose, this recurrence was defined as extending outside the field (EOF). RESULTS: With a median follow-up time of 19 months, the 2-year loco-regional control rate was 69% with primary radiotherapy and 63.5% with surgery followed by irradiation (P = 0.77). The 2-year overall survival rate for the entire patient population was 67.4%. At the time of analysis, 20 of the 72 patients had developed a loco-regional failure; 2 patients (2/20) presented with a loco-regional relapse combined with distant metastasis. Fifteen of the 20 loco-regional failures (15/20) occurred within the high dose region (IF). Five patients (5/20) developed a failure of which the bulky tumour mass was located within the high dose region but extending outside the treatment volume (EOF). No relapses were seen out-field (OF) and no patients relapsed in the spared junctional area contralateral to the tumour. CONCLUSIONS: The selection of patients treated with parotid-sparing radiotherapy, by omitting irradiation to the junctional nodes contralateral to the tumour, proved to be safe in our hands, since no recurrences developed in the spared area. As this parotid-sparing technique reduces significantly the dose to the contralateral parotid and is easy to perform, it should be considered for all selected patients.