Volume Of Salivary Glands Research Articles

Baseline PSMA PET/CT as a predictive biomarker for toxicity and patient-reported outcomes in mCRPC patients undergoing 177Lu-PSMA radioligand therapy.

e17058 Background: The phase III VISION trial demonstrated that 177Lu-PSMA-617 (PSMA-RLT) prolonged overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). Common side effects of PSMA-RLT include xerostomia, bone pain, and myelosuppression. The objective of this study is to evaluate the role of baseline PSMA PET/CT (bPET) in predicting hematologic toxicity and patient-reported outcomes in mCRPC patients undergoing PSMA-RLT. Methods: Patients treated with 177Lu-PSMA-617 in the Expanded Access Program at UCLA with available bPET, toxicity data, and patient-reported outcomes (BPI, FACT-P, and Xerostomia Questionnaire) were included in this retrospective analysis. TRAQinform IQ technology (AIQ Solutions-Madison, WI) was used to conduct region of interest (ROI)-based analyses at bPET. SUVmean, SUVmax, volume (cm3), and total lesion PSMA (TLP; SUVmean x volume) of the whole-body tumor burden, healthy bone, and the salivary glands were extracted. We evaluated the following associations: 1) Whole-body tumor parameters on bPET with time to worsening of FACT-P scores (defined as a decrease of >10 points from baseline) and time to first occurrence of Grade 3 or 4 hematologic toxicity (Multivariate Cox regression model); 2) Healthy bone parameters on bPET with time to worsening of BPI Pain Severity and Pain Interference scores (defined as a 30% increase or at least 2 points from baseline) and time to first occurrence of Grade 3 or 4 hematologic toxicity (Multivariate Cox regression model); 3) Salivary gland parameters on bPET with Xerostomia Questionnaire scores (Mixed-effect linear regression model). Results: 61 mCRPC patients were included. When evaluating associations between healthy bone SUVmean, SUVmax, and TLP with time to first occurrence of Grade 3 or 4 hematologic toxicity, baseline hemoglobin was associated with a longer time to first occurrence (HR = 0.61, p = 0.005; HR = 0.59, p = 0.002; HR = 0.62, p = 0.005 respectively). When evaluating associations between bPET and time to worsening of FACT-P scores, whole-body tumor SUVmean, SUVmax, and TLP were associated with a longer time to worsening (HR = 0.74, p = 0.033; HR = 0.82, p = 0.01; HR = 0.91, p = 0.028 respectively). When evaluating associations between salivary gland SUVmean, volume, SUVmax, and TLP with Xerostomia Questionnaire scores, the number of cycles was associated with higher scores (mean estimate: 0.63, p = 0.003; mean estimate: 0.64, p = 0.003; mean estimate: 0.64, p = 0.003; mean estimate: 0.63, p = 0.003 respectively). Conclusions: In this retrospective analysis of 61 mCRPC patients treated with PSMA-RLT, bPET parameters were generally not predictive of hematologic toxicity or patient-reported outcomes. Of note, whole-body tumor SUV was associated with a longer time to worsening of FACT-P scores. Validation in a larger, prospective cohort is warranted.

Dosimetry of lutetium-177-PSMA-I&T radioligand therapy in recurrent/metastatic adenoid cystic carcinoma.

6093 Background: There is a high unmet need for effective systemic therapies for recurrent and/or metastatic (R/M) adenoid cystic carcinoma (AdCC), as no standard-of-care exists. AdCC frequently expresses prostate-specific membrane antigen (PSMA), providing rationale for PSMA-targeted therapies, which have demonstrated significant efficacy in prostate cancer. In our phase 2 pilot trial (EudraCT 2019-003857-27), we assessed the safety, efficacy and feasibility of lutetium-177 (177Lu)-PSMA-I&T in R/M AdCC patients. Despite well-tolerated, the efficacy was limited. To gain further insight into causes of the limited efficacy, we measured absorbed 177Lu-PSMA-I&T radiation doses in tumors and organs at risk. Methods: Dosimetry was feasible and was performed in all 10 enrolled AdCC patients. They received 177Lu-PSMA-I&T with a median activity of 7.40 (range 6.78-7.49) GBq and a median of 4 (range 1-4) cycles. For bone marrow dosimetry, blood samples were collected during cycle 1. Single-photon emission CT/CT (SPECT/CT) was performed at 1, 24, 48, 72 and 168 hours after 177Lu-PSMA-I&T injection at cycle 1. Tumors >1 cm were categorized based on gallium-68 (68Ga)-PSMA PET mean standardized uptake value (SUVmean): above, at (±10%), and below liver SUVmean. Per site, up to 3 index lesions per category were selected. Volumes of interest with ~1 cm margin were drawn on SPECT/CT. Background correction was applied. Salivary gland and bone lesion volume were determined by iterative thresholding on 68Ga-PSMA PET. Other tumor volumes were determined on CT. Hermes dosimetry software and Olinda 2.2 software were used to estimate doses according to the Medical Internal Radiation Dose scheme. Results were reported as the absorbed dose at cycle 1 (Gy). Results: In total, 66 tumor lesions were analyzed. Tumor sites included lung (n=35), pleura (n=16), liver (n=5), bone (n=4), lymph node (n=3), local recurrence (n=2) and thoracic wall (n=1). The median 68Ga-PSMA PET tumor/liver SUVmean ratio was 0.94 (range 0.33-2.62). The median tumor-absorbed dose was 0.47 (range, 0.01-4.66) Gy. Highest median doses by tumor site were 1.84 (range, 0.76-2.92) Gy in local recurrences and 1.35 (range, 0.33-2.62) Gy in bone lesions. Lowest median doses by tumor site were 0.18 (range, 0.14-0.27) Gy in lymph node lesions and 0.21 (range, 0.12-0.79) Gy in liver lesions. In organs at risk, the absorbed dose was highest in the kidneys, followed by the salivary glands, with mean values of 6.29 (standard deviation [SD], 2.32) Gy and 5.07 (SD, 2.47) Gy, respectively. The mean bone marrow absorbed dose was 0.53 (SD, 0.14) Gy. Conclusions: Tumor-absorbed radiation doses in our AdCC patient cohort receiving 177Lu-PSMA-I&T were significantly lower than in prostate cancer (~10-40 Gy per cycle), likely due to lower and heterogeneous PSMA expression. This could explain the limited efficacy. Organ-absorbed doses aligned with studies in prostate cancer. Clinical trial information: NCT04291300 .

Morphological, Functional and Texture Analysis Magnetic Resonance Imaging Features in the Assessment of Radiotherapy-Induced Xerostomia in Oropharyngeal Cancer

The aim of this single-center, observational, retrospective study was to investigate magnetic resonance imaging (MRI) biomarkers for the assessment of radiotherapy (RT)-induced xerostomia. Twenty-seven patients who underwent radiation therapy for oropharyngeal cancer were divided into three groups according to the severity of their xerostomia—mild, moderate, and severe—clinically confirmed with the Common Terminology Criteria for Adverse Events (CTCAE). No severe xerostomia was found. Conventional and functional MRI (perfusion- and diffusion- weighted imaging) performed both pre- and post-RT were studied for signal intensity, mean apparent diffusion coefficient (ADC) values, k-trans, and area under the perfusion curves. Contrast-enhanced T1 images and ADC maps were imported into 3D slicer software, and salivary gland volumes were segmented. A total of 107 texture features were derived. T-Student and Wilcoxon signed-rank tests were performed on functional MRI parameters and texture analysis features to identify the differences between pre- and post-RT populations. A p-value < 0.01 was defined as acceptable. Receiver operating characteristic (ROC) curves were plotted for significant parameters to discriminate the severity of xerostomia in the pre-RT population. Conventional and functional MRI did not yield statistically significant results; on the contrary, five texture features showed significant variation between pre- and post-RT on the ADC maps, of which only informational measure of correlation 1 (IMC 1) was able to discriminate the severity of RT-induced xerostomia in the pre-RT population (area under the curve (AUC) > 0.7). Values lower than the cut-off of −1.473 × 10−11 were associated with moderate xerostomia, enabling the differentiation of mild xerostomia from moderate xerostomia with a 73% sensitivity, 75% specificity, and 75% diagnostic accuracy. Therefore, the texture feature IMC 1 on the ADC maps allowed the distinction between different degrees of severity of RT-induced xerostomia in the pre-RT population. Accordingly, texture analysis on ADC maps should be considered a useful tool to evaluate salivary gland radiosensitivity and help identify patients at risk of developing more serious xerostomia before radiation therapy is administered.

Sağlıklı Popülasyonda Submandibular Bez Büyüklüğü ile Ağız Sağlığı Durumu, Cinsiyet, Yaş, Beden Kitle İndeksi Arasındaki İlişki: Kesitsel Bir Çalışma

Objective: One of the indexes that best shows the oral health status is the decayed-missing-filled teeth (DMFT) index. 65% of the saliva secreted in the body is produced by the submandibular gland. One of the best imaging methods of the submandibular gland is ultrasound. The aim of this study is to investigate whether there is a relationship between the volume of the submandibular gland, the gland in which saliva is produced the most, and the DMFT index. In addition, changes in the size and volume of the submandibular salivary gland depending on age, gender and body mass index (BMI) were investigated using ultrasonography (USG). Material and Methods: In this study, 240 submandibular glands (right and left) of 120 patients were examined by USG. Results: Submandibular gland volume in males; was found to be higher than that of females (p<0.05). There was no statistically significant relationship between salivary gland volume and BMI, DMFT index (p˃0.05). While the DMFT index increased with age, it did not change depending on gender. We found the mean volume of the right submandibular gland to be 4.21±0.839 cm3 and the volume of the left submandibular gland to average 4.23±0.825 cm3. The mean DMFT index was found to be 11.29±9.025. Conclusion: There is no relationship between submandibular gland size and DMFT index. There is no relationship between submandibular gland size and BMI index. In addition, males have a larger volume of submandibular glands than females.

INFLUENCE OF THE PATIENT’S SEX AND AGE, VOLUMES OF THE SALIVARY GLAND AND PLEOMORPHIC ADENOMA ON THE TUMOR HISTOLOGICAL VARIANTS

Aim: The purpose of the study was to identify the influence of the patient’s sex and age, the volumes of the salivary gland and pleomorphic adenoma on the histological variants of the tumor. Materials and Methods: The study included 21 women and 9 men with pleomorphic adenomas of the salivary gland. In 15 cases, a mesenchymal variant of pleomorphic adenoma was identified, in 5 cases – an epithelial variant, in 10 cases – a mixed variant. The average age of the patients was 39.7±2.9 years. Patients with pleomorphic adenomas underwent magnetic resonance imaging using a Siemens MAGNETOM Aera 1.5T device (Germany), during which three projections of the tumor and salivary gland were measured (antero-posterior, lateral, vertical) with subsequent calculation of their volumes, and then the ratios of these volumes. Classification trees were used to determine whether patients belonged to one of three variants of pleomorphic adenoma. The CART (Classification And Regression Tree) algorithm was used as a branching option. Stopping branching was carried out using the FACT (Fact-style direct stopping) method until each terminal (final) node of the tree does not contain incorrectly classified observations or when their number becomes less than a given proportion of the total group size (less than 5%). Determination of the structure and relationships between the tumor variants and such indicators as gender, age and radiological indicators (volume of the tumor, volume of the salivary gland, ratio of tumor volume to salivary gland volume) was carried out using correspondence analysis. Results: Epithelial variant of pleomorphic adenoma is more typical for women, and the mixed and mesenchymal variant is more common for patients of both sexes. The epithelial variant can develop in patients of any age, while the mixed variant occurs mainly in patients older than 41 years, and the mesenchymal variant – mainly in patients younger than 41 years. The ratio of the volume of the tumor to the volume of the salivary gland will be predominantly &gt;0.17 in the epithelial variant of pleomorphic adenoma, predominantly ≤0.17 in the mesenchymal variant, and can take any value in the mixed variant. Conclusions: The authors conducted a study in order to identify the influence of sex, age of the patient, and the ratio of the volume of pleomorphic adenoma to the volume of the salivary gland on the histological variant of the tumor. The revealed data will be useful in the treatment and diagnostic process in patients with pleomorphic adenoma of the salivary gland.

Cervico-facial Localization of Kimura’s Disease: Two Case Reports and Literature Review

Kimura’s disease is a very rare chronic inflammatory pathology of unknown etiology. It is actually an allergic or autoimmune reaction process involving blood vessels, lymphocytes and eosinophils. We report a first case of Kimura disease with cervical localization in a 37-year-old male Patient who saw the appearance of a swelling of the right parotid region evolving for 2 years. The patient benefited from a total right parotidectomy, the anatomopathological study of the tumoral piece came back in favor of Kimura’s disease. A second case of 20-year-old male Patient who saw the appearance of a 3 swelling of the right pre-auricular region, sub mental region and left cheek region evolving for 5 years. The patient underwent a biopsy of submental swelling, the anatomopathological study confirmed the diagnosis of Kimura’s disease. The patient benefited from a Corticosteroid therapy. The evolution was spectacular, with no recurrence at 12 months follow-up. Kimura’s disease is characterized clinically by subcutaneous nodules of cervicofacial localization, increased volume of salivary glands and satellite adenopathies. Its diagnosis is histological based on the identification of follicular hyperplasia with eosinophilic polynuclear abscesses. Treatment is surgical most often but in some cases Corticosteroid therapy is proposed.

Submandibular gland transfer for the prevention of radiation-induced xerostomia in oropharyngeal cancer: Dosimetric impact in the intensity modulated radiotherapy era.

Submandibular gland (SMG) transfer decreased radiation-associated xerostomia in the 2/3-dimensional radiotherapy era. We evaluated the dosimetric implications of SMG transfer on modern intensity modulated radiotherapy (IMRT) plans. Eighteen oropharynx cancer patients underwent SMG transfer followed by IMRT; reoptimized plans using the baseline SMG location were generated. Mean salivary gland, oral cavity, and larynx doses were compared between clinical plans and reoptimized plans. No statistically significant difference in mean SMG dose (27.53 Gy vs. 29.61 Gy) or total salivary gland dose (26.12 Gy vs. 26.41 Gy) was observed with or without SMG transfer (all p > 0.05). Mean oral cavity and larynx doses were not statistically different. Neither tumor site, target volume crossing midline, stage, nor salivary gland volumes were associated with mean doses. Salivary gland doses were similar with or without SMG transfer. IMRT likely decreases the benefit of SMG transfer on the risk of radiation-associated xerostomia.

Amino Acids May Have Protective Effects on Salivary Glands of 5-FU-administered Mice.

This study aimed to identify the most useful components of Elental® in the treatment of 5-fluorouracil (FU)-induced mucositis and salivary gland atrophy in mice. Mice (except the control group) were intraperitoneally injected with 5-FU. The mice received saline (control group and 5-FU group), dextrin (Dextrin group), amino acids (17AA group), or Elental® (Elental® group). The volume and weight of salivary glands was higher in 17AA and Elental® groups compared to 5-FU group. The number of mucous glands was higher, whereas the number of damaged granular ductal epithelial cells was lower in the salivary glands of all groups except the 5-FU group. Salivation was also decreased in the 5-FU group compared to the other groups. Amino acids could be the most effective components of Elental® for protecting mouse salivary glands from 5-FU-induced atrophic changes, and might be useful in the treatment of oral mucositis in cancer patients.

MR-Guided Adaptive Radiotherapy for Head and Neck Cancer: Prospective Evaluation of Migration and Anatomical Changes of the Major Salivary Glands.

Simple SummaryDuring radiotherapy of head and neck cancer patients, the radiation dose for the major salivary glands (parotids and submandibular glands) should be kept as low as possible to reduce toxicity risks. Nevertheless, volume changes and positional shifts of salivary glands during treatment may result in an increased dose, so adapting the treatment plan is recommended. While previous studies primarily used one or two CTs or CBCTs for imaging during treatment, frequent MRI allows for improved soft tissue contrast and more exact contour adaptation without an additional imaging dose. In this study, twelve patients were treated with MRI-guided radiotherapy with weekly offline adaptations. Significant parotid- and submandibular gland shrinkage, as well as a medial shift of the parotids, were observed. These results support the rationale of MR-guided radiotherapy for head and neck cancer, emphasizing the relevance of future clinical evaluation of toxicity to optimize the benefits of MRI-guided radiotherapy.The aim of this study was to quantify anatomical changes of parotids and submandibular glands and evaluate potential dosimetric advantages during weekly adaptive MR-guided radiotherapy (MRgRT) for the definitive treatment of head and neck cancer (HNC). The data and plans of 12 patients treated with bilateral intensity-modulated radiotherapy for HNC using MR-linac, with weekly offline adaptations, were prospectively evaluated. The positional and volumetric changes of the salivary glands were analyzed by manual segmentation in weekly MRI images and the dosimetric impact of these anatomical changes on the adapted treatment plans was assessed. The mean volume change in parotid and submandibular gland volume was −31.9% (p < 0.0001) and −29.7% (p < 0.0001) after five weeks, respectively. The volume change was significantly correlated with the cumulative dose for the respective gland at the time of volume measurement. Inter-parotid distance changed by −5.4% (6.5 mm) on average after five weeks (p = 0.0005). The distance became significantly smaller only in the left-right direction. The inter-submandibular gland distance changed by 0.7 mm (p = 0.38). This study demonstrated significant changes in salivary gland volumes and position following daily MR guidance and weekly plan adaptation. Ongoing clinical trials will provide data on the clinical impact of these changes and novel MR-based adaptation strategies.

Proton Therapy Specific Salivary Gland Volume Changes After Head and Neck Radiotherapy

Salivary glands are exquisitely sensitive to radiotherapy. Patients treated with radiotherapy to the head and neck region commonly develop salivary gland volume loss and associated xerostomia. Salivary volume loss is associated with salivary function loss, making it a useful surrogate indicator of xerostomia. Previous studies have correlated the degree of salivary gland volume loss with mean radiation doses in patients undergoing photon head and neck radiation. However, change in salivary gland volume relative to radiation dose has not been evaluated in patients undergoing proton therapy. Currently, a constant value of 1.1 is used to relate physical dose (PD) to biological dose (BD) for proton therapy. However, specific tissues may respond differently and thus require a different PD to BD conversion. Herein, we evaluate changes in salivary gland volumes relative to radiation dose in head and neck cancer patients receiving proton therapy to examine the validity of current PD to BD conversions for head and neck salivary glands.Dosimetric data and pre-radiation parotid gland and submandibular gland (SMG) volumes were collected for 20 head and neck cancer patients that received proton therapy at our institution between 2018-2020. Pre-radiation volumes of the SMGs and parotids were collected from treatment planning scans. Post-treatment salivary gland volumes were contoured on 3-month post-treatment diagnostic scans. Mean doses to the glands were gathered from dose-volume histograms generated from treatment plans. Linear logistical regression was performed to measure the effect of dose on volume change.Volume changes of 27 parotids and 38 SMGs were evaluated. Mean doses were 10.0 Gy (standard deviation (SD) 13.2) and 25.2 Gy (SD 25.0) for parotids and SMGs, respectively. Mean dose was < 1 Gy, < 30 Gy, and < 50 Gy in 59.3%, 92.6%, and 100% of parotids compared to 39.5%, 55.3%, and 81.6% of SMGs, respectively. Mean ratios of gland volumes at 3 months post-treatment relative to pre-treatment were 0.962 (SD 0.210) and 1.106 (SD 0.273) for parotids and SMGs, respectively. Effect of mean dose on gland volume change was not statistically significant for either parotids or SMGs.The greater relative size reduction in parotids versus SMGs was consistent with previous photon data. The mean increase in SMG volume could represent post-treatment functional compensation in preserved glands, but this requires additional investigation. Also, determination of the effect of proton dose on salivary gland volume change requires further analysis. Currently, no conclusions can be drawn whether salivary glands are equally or differentially sensitive to proton therapy relative to photon therapy.

High prevalence of salivary gland ultrasound abnormalities in systemic sclerosis

To evaluate salivary gland (SG) involvement in patients with systemic sclerosis (SSc) using SG ultrasound (SGUS). Patients with SSc (n=62), primary Sjögren's syndrome (pSS) (n=59), and idiopathic Sicca syndrome (n=43) were evaluated using the outcome measures in rheumatology clinical trial (OMERACT) definitions of the SGUS scoring system. The hyperechogenic bands using the 0-3 scoring system, intraglandular power Doppler signal (PDS), and SG volumes were also assessed. The proportion of patients with OMERACT grades (≥2) among the four SGs was significantly higher in SSc (51.6%) and pSS (62.7%) groups than those in the idiopathic Sicca syndrome group (4.7%). Patients with SSc and pSS had significantly higher total fibrosis grades than controls. No difference in fibrosis grades was observed between SSc and pSS groups. The PDS scores of SGs were higher in the SSc group than in the idiopathic Sicca syndrome group. SG volumes did not differ between the groups. SSc patients with SGUS grades ≥2 had more anti-centromere antibodies (ACA) (65.6% vs. 30.0%) than individuals with grades 0-1. SSc patients with fibrosis grades ≥2 reported more Sicca symptoms than those with grades 0-1. Inhomogeneity and hyperechogenic bands within the SGs were not associated with organ involvement in SSc. More than half of patients with SSc, specifically with ACA, showed SG involvement. SG fibrosis was more prominent in SSc than in idiopathic Sicca syndrome and was associated with subjective Sicca symptoms. However, hyperechoic bands within the SGs are not features that can differentiate between SSc and pSS.

A longitudinal study on parotid and submandibular gland changes assessed by magnetic resonance imaging and ultrasonography in post-radiotherapy nasopharyngeal cancer patients.

Objectives:With regard to the intensity modulated radiotherapy (IMRT) of nasopharyngeal carcinoma (NPC) patients, this longitudinal study evaluated the radiation-induced changes in the parotid and submandibular glands in terms of gland size, echogenicity and haemodynamic parameters.Methods:21 NPC patients treated by IMRT underwent MRI and ultrasound scans before radiotherapy, and at 6, 12, 18 and 24 months after treatment. Parotid and submandibular gland volumes were measured from the MRI images, whereas the parotid echogenicity and haemodynamic parameters including the resistive index, pulsatility index, peak systolic velocity and end diastolic velocity were evaluated by ultrasonography. Trend lines were plotted to show the pattern of changes. The correlations of gland doses and the post-RT changes were also studied.Results:The volume of the parotid and submandibular glands demonstrated a significant drop from pre-RT to 6 months post-RT. The parotid gland changed from hyperechoic before RT to either isoechoic or hypoechoic after treatment. The resistive index and pulsatility index decreased from pre-RT to 6 month post-RT, then started to increase at 12 month time interval. Both peak systolic velocity and end diastolic velocity increased after 6 months post-RT then followed a decreasing trend up to 24 months post-RT. There was mild correlation between post-RT gland dose and gland volume, but not with haemodynamic changes.Conclusions:Radiation from IMRT caused shrinkage of parotid and submandibular glands in NPC patients. It also changed the echogenicity and vascular condition of the parotid gland. The most significant changes were observed at 6 months after radiotherapy.Advances in knowledge:It is the first paper that reports on the longitudinal changes of salivary gland volume, echogenicity and haemodynamic parameters altogether in NPC patients after radiotherapy. The results are useful for the prediction of glandular changes that is associated with xerostomia, which help to provide timely management of the complication when the patients attend follow-up visits.

Xerostomia, salivary characteristics and gland volumes following intensity‐modulated radiotherapy for nasopharyngeal carcinoma: a two‐year follow up

To evaluate changes in xerostomia status, salivary characteristics and gland volumes 2 years following radiotherapy in nasopharyngeal carcinoma patients. Xerostomia scores, salivary flow rates, pH and buffering capacity were measured at pre-radiotherapy, mid-radiotherapy, 2 weeks, 3 months and 2 years post-radiotherapy. Salivary gland volumes and their correlation with radiation dose were also assessed. Mean radiation dose to oral cavity, parotid and submandibular glands (SMG) was 44.5, 65.0 and 38.6 Gy respectively. Parotid and SMG volumes decreased 33% at 3 months post-radiotherapy; volumes at 2 years post-radiotherapy were 84% and 51% of pre-radiotherapy levels, respectively. Correlations were observed between parotid gland volume per cent reduction and its radiation dose and between resting salivary flow rate reduction and post-radiotherapy/pre-radiotherapy SMG volume ratio. Salivary flow rates and resting saliva pH remained significantly low at 2 years post-radiotherapy (both flow rates, P = 0.001; resting saliva pH, P = 0.005). Similarly, xerostomia scores remained significantly higher compared with pre-radiotherapy levels. Submandibular gland volumetric shrinkage persisted 2 years after radiotherapy. Xerostomia scores remained significantly higher, and salivary flow rates and resting saliva pH remained significantly lower, suggesting that study participants were still at risk for hyposalivation-related oral diseases.

Treatment of immunoglobulin G4-related sialadenitis: outcomes of glucocorticoid therapy combined with steroid-sparing agents

BackgroundImmunoglobulin G4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated systemic disease. Despite its good response to steroid therapy, its treatment protocol is not standardized and the long-term outcome is controversial. The study was conducted to determine the short-term and long-term outcomes of IgG4-RS patients treated with glucocorticoids and steroid-sparing immunosuppressive agents, to analyze secretory function, serological and radiological changes in salivary glands and to assess the usefulness of serum IgG4 level as an indicator of disease activity.MethodsIgG4-RS patients who were treated for more than 3 months were enrolled. Serological tests, salivary gland function assessment and computed tomography (CT) were performed before treatment and during follow up. The treatment outcomes in the short and the long term were evaluated, and the relationship between serum IgG4 level and salivary gland volume was analyzed.ResultsGlucocorticoids were used in all 43 patients and steroid-sparing immunosuppressive agents in 38 patients (88.4%). The follow-up period was 24.6 ± 14.9 months. Clinical remission was achieved in all patients after induction therapy. During short-term observation, salivary gland secretion significantly increased, and the serum IgG4 levels, the volumes and CT values of submandibular and parotid gland decreased significantly (P < 0.001). For long term, relapse occurred in 32.5% patients within 55 months in the regularly treated group, while all seven irregularly treated patients relapsed. However, the relapse-free survival curves were not significantly different between the steroid monotherapy and the combination therapy groups (P = 0.566). Submandibular glands, lacrimal glands, sublingual glands, nasal and paranasal cavity were commonly relapsing organs. In clinically stable patients, a serologically unstable condition occurred in 54.9% patients within 55 months and medication adjustment was performed accordingly. Volume changes in the submandibular and parotid glands were associated with serum IgG4 levels and time of follow up (R2adjusted = 0.905, P < 0.0001 and R2adjusted = 0.9334, P < 0.0001, respectively).ConclusionsThe combination of glucocorticoid and steroid-sparing agents could be effective for treating IgG4-RS, and restoring salivary gland function. Serum IgG4 levels could predict disease activity.

Radiation therapy and serum salivary amylase in head and neck cancer.

Radiation therapy (RT) is a valid treatment option for head and neck cancer (HNC). The risk of RT-induced toxicities is significant, especially due to extended treatment fields. The raise in amylase activity is strictly dependent on the volume of salivary glands included in the irradiated target volume and it is firmly related to the dose. The aim of this review is to report the effects on salivary amylase activity after radiation exposure of salivary glands, in patients with HNC.

Interests of the ultrasound-guidance in the treatment of drooling through botulinum toxin injections, our experience over 10years

To report about our 10years' experience about the treatment of drooling by ultrasound guided botulinum toxin injections. Retrospective monocentric study including all the patients suffering from drooling and treated by ultrasound-guided botulinum toxin injections into the salivary glands between 2004and 2015. The etiology of r drooling, the doses of toxin, the injected glands, the size of the glands measured by ultrasonography, the effectiveness of the treatment and the side effects were assessed. Two hundred and ninety-two injections sessions were performed in 61patients. Exactly 70.5% of patients reported an improvement after the first session. Parkinson's disease was the main etiology of drooling (43% of the patients). Eleven patients reported side effects. The salivary gland volume reduced after treatment in 46% of the patients. The interest of ultrasound-guidance is to make sure about the intraglandular injection, to lower the risk for extraglandular diffusion of the toxin responsible for swallowing disorders and to allow for an adaptation of the doses to the volume of the salivary glands, which may vary during treatment.

Post-therapeutic dosimetry of 177Lu-DKFZ-PSMA-617 in the treatment of patients with metastatic castration-resistant prostate cancer.

Lu-DKFZ-PSMA-617, a urea-based compound, binds to the extracellular domain of prostate-specific membrane antigen, thus providing an effective target for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Before its therapeutic use, it is necessary that the radiation dosimetry of this radiopharmaceutical be studied to determine the safe activity that can be administered in patients to prevent haematological, renal and liver toxicity. The present study thus aimed to assess the pharmacokinetics and dosimetry of Lu-DKFZ-PSMA-617 in CRPC patients. After obtaining ethical clearance from the institute ethics review board, we enrolled mCRPC patients who were positive on a Glu-NH-CO-NH-Lys-(Ahx)-[Ga(HBED-CC)] PET/CT scan. For kidney protection, a cocktail of lysine and arginine diluted in 2 litres of normal saline was infused, starting from 30 to 60 min before Lu-DKFZ-PSMA-617 infusion. The mean administered activity in the overall population was 2.52±1.3 GBq. For the purpose of dosimetry, each patient underwent nine planar whole-body scans along with blood and urine sample collection at 0.5, 3.5, 24, 48, 72, 96, 120, 144 and 168 h, respectively. SPECT/CT was performed to derive the volume of salivary glands (parotid and submandibular glands) and tumour. Dosimetric evaluation was carried out using the OLINDA/EXM 1.0 software. A total of 26 mCRPC patients with a mean age of 66.30±9.95 years (range: 38-81 years) were recruited. Normal physiological uptake was observed in all the patients in the lacrimal glands, salivary glands (parotid glands and submandibular glands), liver, spleen, kidneys, intestines and urinary bladder. Organs with the highest absorbed doses were the salivary glands, followed by the kidneys, receiving 1.24±0.26 and 0.99±0.31 mGy/MBq, respectively. The mean absorbed doses to the liver, urinary bladder and red marrow were 0.36±0.10, 0.243±0.09 and 0.048±0.05 mGy/MBq, respectively. The mean whole-body dose was 0.016±0.003 mGy/MBq. Lu-DKFZ-PSMA-617 therapy is a safe option in the treatment of mCRPC patients.

Intensity-modulated radiotherapy or volumetric-modulated arc therapy in patients with head and neck cancer: Focus on salivary glands dosimetry.

Despite radiotherapy (RT) technical improvements, high salivary dysfunction rates are still reported in patients with head and neck squamous cell carcinoma (HNSCC). The purpose of the present study was to report salivary glands dosimetry with volumetric-modulated arc therapy (VMAT) and intensity-modulated RT (IMRT). Dosimetry of consecutive patients receiving IMRT or VMAT for proven HNSCC between 2007 and 2013 were retrospectively reviewed. Data of 609 patients were studied. Mean dose, mean maximum dose, and mean percentage of salivary gland volume receiving at least 26 Gy (V26) of the contralateral parotid were 24.50 Gy (range, 0-70.4 Gy), 39.08 Gy (range, 0.38-76.45 Gy), and 40.92% (range, 0% to 100%), respectively. Mean and maximum dose on contralateral submandibular gland were 48.18 Gy (range, 0.19-70.73 Gy), and 61.25 Gy (range, 0-75.8 Gy), respectively. Target volume coverage still has to be prioritized over organs at risk (OAR) sparing with new RT techniques. Submandibular glands are not sufficiently taken into account in guidelines. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1028-1034, 2016.

Radiation-Induced Volumetric Changes of Salivary Glands in Relation With Mean Dose and Saliva Production in Head and Neck Cancer Patients

Radiation-Induced Volumetric Changes of Salivary Glands in Relation With Mean Dose and Saliva Production in Head and Neck Cancer Patients

Xerostomia.

Xerostomia is the subjective feeling of oral dryness. The major causes are Sjögren's syndrome (SS), medication and radiotherapy to the head and neck. SS is a chronic systemic autoimmune disease characterized by infiltration of the exocrine glands, the salivary and lacrimal ones in particular. The pathogenesis involves systemic B cell hyperactivity and T cell lymphocytes targeting glandular epithelial cells. About 7.5% of patients with SS develop malignant B cell lymphoma, mostly mucosa-associated tissue lymphomas. Certain classes of drugs can induce hyposalivation and/or xerostomia by, e.g., targeting neurotransmitters and receptors. As a result, amongst others the production of fluid and electrolytes in salivary glands can be reduced and the salivary composition can change. During head and neck radiotherapy, the administration of high doses to the major salivary glands, which are located in the periphery of the head, leads to progressive loss of glandular function and a diminished salivary output. Reduction of the dose and the volume of irradiated salivary glands by advanced radiotherapy techniques can be highly beneficial for patients.