Xerostomia is a common post-radiotherapy (post-RT) complication in nasopharyngeal carcinoma (NPC) patients. This study evaluated the relation of post-RT parotid gland changes with the dose received.
Data from 18 NPC patients treated by radiotherapy between 1997 and 2001 were collected. Parotid gland volumes were measured and compared between their pre-RT and post-RT CT images; both sets of CT were conducted with the same scanning protocol. Doppler ultrasound was used to assess the haemodynamic condition of the glands after radiotherapy. Doppler ultrasound results were compared against 18 age-matched normal participants. A questionnaire was used to evaluate the patients' comments of xerostomia condition. Radiotherapy treatment plans of the participants were retrieved from the Eclipse treatment planning system from which the radiation doses delivered to the parotid glands were estimated. The correlations of parotid gland doses and the post-RT changes were evaluated.
The post-RT parotid glands were significantly smaller (p<0.001) than the pre-RT ones. They also demonstrated lower vascular velocity, resistive and pulsatility indices (p<0.05) than normal participants. The degree of volume shrinkage and subjective severity of xerostomia demonstrated dose dependence, but such dependence was not definite in the haemodynamic changes.
It was possible to predict the gland volume change and subjective severity of xerostomia based on the dose to the parotid glands for NPC patients. However, such prediction was not effective for the vascular changes. The damage to the gland was long lasting and had significant effects on the patients' quality of life.
Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia.
We undertook a randomised controlled trial between Jan 21, 2003, and Dec 7, 2007, that compared conventional radiotherapy (control) with parotid-sparing IMRT. We randomly assigned patients with histologically confirmed pharyngeal squamous-cell carcinoma (T1–4, N0–3, M0) at six UK radiotherapy centres between the two radiotherapy techniques (1:1 ratio). A dose of 60 or 65 Gy was prescribed in 30 daily fractions given Monday to Friday. Treatment was not masked. Randomisation was by computer-generated permuted blocks and was stratified by centre and tumour site. Our primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months, as assessed by the Late Effects of Normal Tissue (LENT SOMA) scale. Analyses were done on an intention-to-treat basis, with all patients who had assessments included. Long-term follow-up of patients is ongoing. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN48243537.
47 patients were assigned to each treatment arm. Median follow-up was 44·0 months (IQR 30·0–59·7). Six patients from each group died before 12 months and seven patients from the conventional radiotherapy and two from the IMRT group were not assessed at 12 months. At 12 months xerostomia side-effects were reported in 73 of 82 alive patients; grade 2 or worse xerostomia at 12 months was significantly lower in the IMRT group than in the conventional radiotherapy group (25 [74%; 95% CI 56–87] of 34 patients given conventional radiotherapy vs 15 [38%; 23–55] of 39 given IMRT, p=0·0027). The only recorded acute adverse event of grade 2 or worse that differed significantly between the treatment groups was fatigue, which was more prevalent in the IMRT group (18 [41%; 99% CI 23–61] of 44 patients given conventional radiotherapy vs 35 [74%; 55–89] of 47 given IMRT, p=0·0015). At 24 months, grade 2 or worse xerostomia was significantly less common with IMRT than with conventional radiotherapy (20 [83%; 95% CI 63–95] of 24 patients given conventional radiotherapy vs nine [29%; 14–48] of 31 given IMRT; p<0·0001). At 12 and 24 months, significant benefits were seen in recovery of saliva secretion with IMRT compared with conventional radiotherapy, as were clinically significant improvements in dry-mouth-specific and global quality of life scores. At 24 months, no significant differences were seen between randomised groups in non-xerostomia late toxicities, locoregional control, or overall survival.
Sparing the parotid glands with IMRT significantly reduces the incidence of xerostomia and leads to recovery of saliva secretion and improvements in associated quality of life, and thus strongly supports a role for IMRT in squamous-cell carcinoma of the head and neck.
Cancer Research UK (CRUK/03/005).
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.
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.
A high dose of 66 Gy causes irreversible damage to parotid salivary duct system.
Radiotherapy; Head and neck cancer; Parotid gland; Sodium
A common side effect experienced by head and neck cancer patients after radiotherapy (RT) is impairment of the parotid glands’ ability to produce saliva. Our purpose is to investigate the relationship between radiation dose and saliva changes in the two years following treatment.
Methods and Materials
The study population includes 142 patients treated with conformal or intensity modulated radiotherapy. Saliva flow rates from 266 parotid glands are measured before and 1, 3, 6, 12, 18 and 24 months after treatment. Measurements are collected separately from each gland under both stimulated and unstimulated conditions. Bayesian nonlinear hierarchical models were developed and fit to the data.
Parotids receiving higher radiation produce less saliva. The largest reduction is at 1–3 months after RT followed by gradual recovery. When mean doses are lower (e.g. <25Gy), the model-predicted average stimulated saliva recovers to pre-treatment levels at 12 months and exceeds it at 18 and 24 months. For higher doses (e.g. >30Gy), the stimulated saliva does not return to original levels after two years. Without stimulation, at 24 months, the predicted saliva is 86% of pre-treatment levels for 25Gy and <31% for >40Gy. We do not find evidence to support that the over-production of stimulated saliva at 18 and 24 months after low dose in one parotid gland is due to low saliva production from the other parotid gland.
Saliva production is impacted significantly by radiation, but with doses <25–30Gy, recovery is substantial and returns to pre-treatment levels two years after RT.
Head and neck cancer; Intensity modulated radiation therapy; Parotid salivary glands; Radiation dose; Bayesian analysis
To evaluate the feasibility of image-guided radiotherapy based on helical Tomotherapy to spare the contralateral parotid gland in head and neck cancer patients with unilateral or no neck node metastases.
A retrospective review of 52 patients undergoing radiotherapy for head and neck cancers with image guidance based on daily megavoltage CT imaging with helical tomotherapy was performed.
Mean contralateral parotid dose and the volume of the contralateral parotid receiving 40 Gy or more were compared between radiotherapy plans with significant constraint (SC) of less than 20 Gy on parotid dose (23 patients) and the conventional constraint (CC) of 26 Gy (29 patients). All patients had PTV coverage of at least 95% to the contralateral elective neck nodes. Mean contralateral parotid dose was, respectively, 14.1 Gy and 24.7 Gy for the SC and CC plans (p < 0.0001). The volume of contralateral parotid receiving 40 Gy or more was respectively 5.3% and 18.2% (p < 0.0001)
Tomotherapy for head and neck cancer minimized radiotherapy dose to the contralateral parotid gland in patients undergoing elective node irradiation without sacrificing target coverage.
Head and neck cancer; Tomotherapy; Parotid sparing
The aim of the present study was to evaluate the recovery potential of the parotid glands after using either 3D-conformal-radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) by sparing one single parotid gland.
Between 06/2002 and 10/2008, 117 patients with head and neck cancer were included in this prospective, non-randomised clinical study. All patients were treated with curative intent. Salivary gland function was assessed by measuring stimulated salivary flow at the beginning, during and at the end of radiotherapy as well as 1, 6, 12, 24, and 36 months after treatment. Measurements were converted to flow rates and normalized relative to rates before treatment. Mean doses (Dmean) were calculated from dose-volume histograms based on computed tomographies of the parotid glands.
Patients were grouped according to the Dmean of the spared parotid gland having the lowest radiation exposure: Group I - Dmean < 26 Gy (n = 36), group II - Dmean 26-40 Gy (n = 45), and group III - Dmean > 40 Gy (n = 36). 15/117 (13%) patients received IMRT. By using IMRT as compared to 3D-CRT the Dmean of the spared parotid gland could be significantly reduced (Dmean IMRT vs. 3D-CRT: 21.7 vs. 34.4 Gy, p < 0.001). The relative salivary flow rates (RFSR) as a function of the mean parotid dose after 24 and 36 months was in group I 66% and 74%, in group II 56% and 49%, and in group III 31% and 24%, respectively. Multiple linear regression analyses revealed that the parotid gland dose and the tumor site were the independent determinants 12 and 36 months after the end of RT. Patients of group I and II parotid gland function did recover at 12, 24, and 36 months after the end of RT.
If a Dmean < 26 Gy for at least one parotid gland can be achieved then this is sufficient to reach complete recovery of pre-RT salivary flow rates. The radiation volume which depends on tumor site did significantly impact on the Dmean of the parotids, and thus on the saliva flow and recovery of parotid gland.
head and neck cancer; irradiation; saliva; hyposalivation; parotid gland sparing; recovery
Malignant tumours of the parotid gland represent a group of relatively rare lesions. The medical records of 363 patients with parotid swelling treated between 1974 and 2003 at the “G. Ferreri” Department of Otorhinolaryngology, “La Sapienza” University in Rome were retrospectively analysed. Clinical presentation, pre-operative investigations, surgical procedure, histopathology report, post-operative complications, and the oncological results of 19 patients who underwent extended radical parotidectomy for malignant neoplasm of the parotid gland are discussed. Extended radical parotidectomy, reserved for neoplasms in an advanced stage, involves the removal of the entire parotid gland, with sacrifice of the facial nerve and the resection en bloc of the adjacent structures affected by neoplastic infiltration, such as the temporal bone, the mandibular bone, the skin, blood vessels and nerves. In addition to this surgical treatment, a cycle of adjuvant radiotherapy is also necessary. The overall rate of survival at 10 years depends mainly on the histological characteristics of the tumour, and, in this series, is reported to be approximately 58%. These data indicate that total extended radical parotidectomy combined with post-operative radiotherapy, represents the best therapeutic approach with regard both to quality of life and life expectancy, in patients with an advanced stage of malignant neoplasm of the parotid gland.
Parotid gland; Malignant tumours; Treatment; Extended parotidectomy
To analyse the combined and updated results from the University of Michigan and University Medical Center Utrecht on normal tissue complication probability (NTCP) of the parotid gland one year after radiotherapy (RT) for head and neck (HN) cancer.
Materials and methods
222 prospectively analyzed patients with various HN malignancies were treated with conventional and intensity-modulated RT. Stimulated individual parotid gland flow rates were measured before RT and one year after RT using Lashley cups at both centers. A flow ratio <25% of pre-treatment was defined as a complication. The data were fitted to the Lyman-Kutcher-Burman (LKB) model.
A total of 384 parotid glands (Michigan: 157; Utrecht: 227 glands) was available for analysis one year after RT. Combined NTCP analysis based on mean dose resulted in TD50 (uniform dose leading to 50% complication probability) of 39.9 Gy and m (steepness of the curve) of 0.40. The resulting NTCP curve had good qualitative agreement with the combined clinical data. Mean doses 25-30 Gy were associated with 17-26% NTCP.
A definite NTCP curve for parotid gland function one year after RT is presented based on mean dose. No threshold dose was observed and TD50 was equal to 40 Gy.
Parotid gland function; xerostomia; radiotherapy; NTCP; head-and-neck cancer
Clear cell Hidradenocarcinoma is a rare carcinoma arising from sweat glands. It is an aggressive tumor that most metastasizes to regional lymph nodes and distant viscera; surgery with safe margins is the mainstay of treatment.
We report a case of 68-year-old woman who presented with an invasive clear cell hidradenocarcinoma situated in the left parotid area which recurred 5 months after surgery, this recurrence was managed successfully by high-dose irradiation of the tumor bed (66 Gy) and regional lymphatic chains (50 Gy), after a follow-up of more than 15 months, the patient is in good local control without significant toxicity.
Post operative radiotherapy allows better local control and should be mandatory when histological features predictive of recurrence are present: positive margins, histology poorly differentiated, perineural invasion, vascular and lymphatic invasion, lymph node involvement, and extracapsular spread.
Hidradenocarcinoma; sweat-gland; rare; surgery; recurrence; megavoltage external beam radiotherapy
Rab3D, a member of the Rab3 subfamily of the Rab/ypt GTPases, is expressed on zymogen granules in the pancreas as well as on secretory vesicles in mast cells and in the parotid gland. To shed light on the function of Rab3D, we have generated Rab3D-deficient mice. These mice are viable and have no obvious phenotypic changes. Secretion of mast cells is normal as revealed by capacitance patch clamping. Furthermore, enzyme content and overall morphology are unchanged in pancreatic and parotid acinar cells of knockout mice. Both the exocrine pancreas and the parotid gland show normal release kinetics in response to secretagogue stimulation, suggesting that Rab3D is not involved in exocytosis. However, the size of secretory granules in both the exocrine pancreas and the parotid gland is significantly increased, with the volume being doubled. We conclude that Rab3D exerts its function during granule maturation, possibly by preventing homotypic fusion of secretory granules.
Adenoid cystic carcinoma of the parotid gland is a rare and slowly growing, but highly malignant tumor. Surgical resection of a malignant parotid tumor should include resection of the facial nerve when the nerve is involved in the tumor. Facial nerve reconstruction is required after nerve resection. A 14 year-old female presented with complaints of painless enlargement of the right parotid gland and facial asymmetry. Physical examination revealed a firm mass in the region of the parotid gland as well as right facial paralysis. Biopsy obtained from the mass showed an adenoid cystic carcinoma of the parotid gland. A radical parotidectomy with a modified radical neck dissection was carried out. Grafting material for the facial reconstruction was harvested from the great auricular nerve. The proximal main trunk and each distal branch of the facial nerve were coapted with the greater auricular nerve. The patient received radiotherapy after surgery and was seen to achieve grade IV facial function one year after surgery. Thus, the great auricular nerve is appropriate grafting material for coaptation of each distal branch of the facial nerve.
Adenoid cystic carcinoma; facial nerve reconstruction; parotid gland; radiotherapy
To quantify the differences between planned and delivered parotid gland and target doses, and to assess the benefits of daily bone alignment for head-and-neck cancer patients treated with intensity-modulated radiotherapy (IMRT).
Methods and Materials
Eleven head-and-neck cancer patients received 2 CT scans/week with an in-room CT scanner over their course of radiotherapy. The clinical IMRT plans, designed with 3–4mm planning margins, were recalculated on the repeat CT images. The plans were aligned using (1) the actual treatment isocenter marked with radiopaque markers (BB) and (2) bone alignment to the cervical vertebrae to simulate image-guided setup. In-house deformable image registration software was used to map daily dose distributions to the original treatment plan and to calculate a cumulative, delivered dose distribution for each patient.
Using conventional BB alignment led to increases in the parotid gland mean dose above the planned dose by 5–7Gy in 45% of the patients (median = 3.0Gy ipsilateral (p=0.026); median = 1.0Gy contralateral (p=0.016)). Use of bone alignment led to reductions relative to BB alignment in 91% of patients (median=2Gy; range=0.3–8.3Gy; 15 of 22 parotids improved). However, the parotid dose from bone alignment was still greater than planned (median=1.0Gy (p=0.007)). Neither approach affected tumor dose coverage.
With conventional BB alignment, the parotid gland mean dose was significantly increased above the planned mean dose. Using daily bone alignment reduced the parotid dose compared to BB alignment in almost all patients. A 3–4 mm planning margin was adequate for tumor dose coverage.
adaptive radiotherapy; IGRT; setup uncertainty; anatomic variation; parotid gland
Background and purpose
To assess the impact of intensity modulated radiotherapy (IMRT) versus conventional radiation on late xerostomia and Quality of Life aspects in head and neck cancer patients.
Patients and nethods
Questionnaires on xerostomia in rest and during meals were sent to all patients treated between January 1999 and December 2003 with a T1-4, N0-2 M0 head and neck cancer, with parotid gland sparing IMRT or conventional bilateral neck irradiation to a dose of at least 60 Gy, who were progression free and had no disseminated disease (n = 192). Overall response was 85% (n = 163); 97% in the IMRT group (n = 75) and 77% in the control group (n = 88) the median follow-up was 2.6 years. The prevalence of complaints was compared between the two groups, correcting for all relevant factors at multivariate ordinal regression analysis.
Patients treated with IMRT reported significantly less difficulty transporting and swallowing their food and needed less water for a dry mouth during day, night and meals. They also experienced fewer problems with speech and eating in public. Laryngeal cancer patients in general had fewer complaints than oropharynx cancer patients but both groups benefited from IMRT. Within the IMRT group the xerostomia scores were better for those patients with a mean parotid dose to the "spared" parotid below 26 Gy.
Parotid gland sparing IMRT for head and neck cancer patients improves xerostomia related quality of life compared to conventional radiation both in rest and during meals. Laryngeal cancer patients had fewer complaints but benefited equally compared to oropharyngeal cancer patients from IMRT.
The exposure to high doses of ionizing radiation during radiotherapy results in severe morphological and functional alterations of the salivary glands, such as xerostomia. In the present study we investigated the chronic effect of a single radiation dose of 15 Gray (Gy) limited to head and neck on rat salivary gland function (salivary secretion and gland mass) and histology. Results indicate that norepinephrine (NE)-induced salivary secretion was reduced significantly at 30, 90, 180 and 365 days after the administration of a single dose of 15 Gy of ionizing radiation compared to non-irradiated animals. The maximal secretory response was reduced by 33% at 30 and 90 days post irradiation. Interestingly, a new fall in the salivary response to NE was observed at 180 days and was maintained at 365 days post irradiation, showing a 75% reduction in the maximal response. The functional fall of the salivary secretion observed at 180 days post irradiation was not only associated with a reduction of gland mass but also to an alteration of the epithelial architecture exhibiting a changed proportion of ducts and acini, loss of eosinophilic secretor granular material, and glandular vacuolization and fibrosis. On the basis of the presented results, we conclude that ionizing radiation produces irreversible and progressive alterations of submandibular gland (SMG) function and morphology that leads to a severe salivary hypo-function.
Radiotherapy; xerostomia; submandibular gland; salivary secretion.
Parotid gland metastasis in breast cancer is extremely rare, and only 14 cases have been reported between 1982 and 2010.
A 67-year-old female patient was diagnosed with invasive lobular carcinoma of the left breast. Although clinical staging was T1N3M1 (stage IV), the tumor experienced a complete response to chemotherapy. We therefore performed a mastectomy followed by radiotherapy, and continued administration of trastuzumab. However, 11 months later, the patient complained of a swelling in the left parotid gland. Histology following a partial parotidectomy revealed a parotid gland metastasis from the breast.
Treatment with capecitabine in addition to trastuzumab, which is one of the strategies applied in HER2-positive breast cancer, was effective in our patient. Analysis of the 14 cases of parotid gland metastasis from the breast reported between 1982 and 2010 revealed that the metastasis may occur not by direct lymphatic but by hematogenous spread.
Parotid gland metastasis; Breast cancer; Trastuzumab
To relate the development of post-treatment hypothyroidism with the dose distribution within the thyroid gland in breast cancer (BC) patients treated with loco-regional radiotherapy (RT).
Methods and materials
In two groups of BC patients postoperatively irradiated by computer tomography (CT)-based RT, the individual dose distributions in the thyroid gland were compared with each other; Cases developed post-treatment hypothyroidism after multimodal treatment including 4-field RT technique. Matched patients in Controls remained free for hypothyroidism. Based on each patient's dose volume histogram (DVH) the volume percentages of the thyroid absorbing respectively 20, 30, 40 and 50 Gy were then estimated (V20, V30, V40 and V50) together with the individual mean thyroid dose over the whole gland (MeanTotGy). The mean and median thyroid dose for the included patients was about 30 Gy, subsequently the total volume of the thyroid gland (VolTotGy) and the absolute volumes (cm3) receiving respectively < 30 Gy and ≥ 30 Gy were calculated (Vol < 30 and Vol ≥ 30) and analyzed.
No statistically significant inter-group differences were found between V20, V30, V40 and V50Gy or the median of MeanTotGy. The median VolTotGy in Controls was 2.3 times above VolTotGy in Cases (ρ = 0.003), with large inter-individual variations in both groups. The volume of the thyroid gland receiving < 30 Gy in Controls was almost 2.5 times greater than the comparable figure in Cases.
We concluded that in patients with small thyroid glands after loco-radiotherapy of BC, the risk of post-treatment hypothyroidism depends on the volume of the thyroid gland.
Breast cancer; Radiotherapy; hypothyroidism
Oral changes following radiotherapy are not uncommon. Oral mucositis, alteration in salivary gland function, radiation caries, and gingival changes have all been reported following radiotherapy and chemotherapy. The gingival changes seen after radiotherapy may be unusual and often cause diagnostic dilemma. Metastasis to the gingiva has also to be ruled out in these cases. A 30-year-old female patient presented with enlargement of the gingiva of 6 months’ duration and lower lip swelling of 7 months’ duration. She was a known case of carcinoma of nasopharynx and had received radiotherapy and chemotherapy. Based on the history, the clinical appearance of the gingiva, and the other oral changes we considered both post-radiotherapy gingival enlargement and secondary metastasis to gingiva as possibilities. An incisional biopsy was performed (internal bevel gingivectomy). The histopathological report did not reveal any metastatic changes. Thus, we diagnosed post-radiotherapy gingival enlargement. For the multiple carious teeth, extraction and root canal treatment was carried out as necessary. The patient was referred to the department of Oral and Maxillofacial Surgery for management of swelling of the lips, which was diagnosed as lymphedema of the lip. Gingival enlargement is rare post radiotherapy. Such nonplaque-associated gingival enlargement in a patient who has undergone radiotherapy should be subjected to biopsy and histopathological examination to distinguish between secondary metastasis and post-radiation changes.
Gingival enlargement; metastasis; nasopharynx carcinoama; radiotherapy
To investigate the potential of parotic gland sparing of intensity modulated radiotherapy (3D-c-IMRT) performed with metallic compensators for head and neck cancer in a clinical series by analysis of dose distributions and clinical measures.
Materials and methods
39 patients with squamous cell cancer of the head and neck irradiated using 3D-c-IMRT were evaluable for dose distribution within PTVs and at one parotid gland and 38 patients for toxicity analysis. 10 patients were treated primarily, 29 postoperatively, 19 received concomittant cis-platin based chemotherapy, 20 3D-c-IMRT alone. Initially the dose distribution was calculated with Helax ® and photon fluence was modulated using metallic compensators made of tin-granulate (n = 22). Later the dose distribution was calculated with KonRad ® and fluence was modified by MCP 96 alloy compensators (n = 17). Gross tumor/tumor bed (PTV 1) was irradiated up to 60–70 Gy, [5 fractions/week, single fraction dose: 2.0–2.2 (simultaneously integrated boost)], adjuvantly irradiated bilateral cervical lymph nodes (PTV 2) with 48–54 Gy [single dose: 1.5–1.8]). Toxicity was scored according the RTOG scale and patient-reported xerostomia questionnaire (XQ).
Mean of the median doses at the parotid glands to be spared was 25.9 (16.3–46.8) Gy, for tin graulate 26 Gy, for MCP alloy 24.2 Gy. Tin-granulate compensators resulted in a median parotid dose above 26 Gy in 10/22, MCP 96 alloy in 0/17 patients. Following acute toxicities were seen (°0–2/3): xerostomia: 87%/13%, dysphagia: 84%/16%, mucositis: 89%/11%, dermatitis: 100%/0%. No grade 4 reaction was encountered. During therapy the XQ forms showed °0–2/3): 88%/12%. 6 months postRT chronic xerostomia °0–2/3 was observed in 85%/15% of patients, none with °4 xerostomia.
3D-c-IMRT using metallic compensators along with inverse calculation algorithm achieves sufficient parotid gland sparing in virtually all advanced head and neck cancers. Since the concept of lower single (and total) doses in the adjuvantly treated volumes reduces acute morbidity 3D-c-IMRT nicely meets demands of concurrent chemotherapy protocols.
The challenges of lung cancer radiotherapy are intra/inter-fraction tumor/organ anatomy/motion changes and the
need to spare surrounding critical structures. Evolving radiotherapy technologies, such as four-dimensional (4D) image-based motion management, daily on-board imaging and adaptive radiotherapy based on volumetric images over the course of radiotherapy, have enabled us to deliver higher dose to target while minimizing normal tissue toxicities. The image-guided radiotherapy adapted to changes of motion and anatomy has made the radiotherapy more precise and allowed ablative dose delivered to the target using novel treatment approaches such as intensity-modulated radiation therapy, stereotactic body radiation therapy, and proton therapy in lung cancer, techniques used to be considered very sensitive to motion change. Future clinical trials using real time tracking and biological adaptive radiotherapy based on functional images are proposed.
Mucoepidermoid tumors are salivary gland neoplasms located mainly in the parotid gland. We present an unusual case of such a tumor arising from the middle ear and mastoid cavity successfully treated by surgery and post-operative radiotherapy.
Mucoepidermoid tumor; mastoid
Parotid fistula is a well known complication of parotidectomy or penetrating injury of the parotid gland. Fistulae may be internal or external, but simple internal fistulae are of no surgical interest. In cases of external fistulae, the principles of management aim at the return of normal parotid function in both acute and chronic parotid injury, but sometimes the alternative is to depress parotid secretions to allow natural healing process to seal the injury.
The paper highlights the indications, techniques, advantages and disadvantages of using osmotic sclerosant for the management of parotid fistulae. We used warm hypertonic saline injections within the glandular substance to cause rapid fibrosis of the gland in 2 patients of chronic parotid fistulae.
This technique is a simple and effective method of dealing with salivary leak. Its ease of performance, effectiveness; minimal surgical risk and minor cost are the advantages over other available options.
Salivary fistula; Sialocele; Hypertonic saline; Osmotic sclerosants
Background and Purpose
Various radiotherapy planning methods for locally advanced squamous cell carcinoma of the head and neck (SCCHN) have been proposed to decrease normal tissue toxicity. We compare IMRT, adaptive IMRT, proton therapy (IMPT), and adaptive IMPT for SCCHN.
Materials and Methods
Initial and re-simulation CT images from 10 consecutive patients with SCCHN were used to quantify dosimetric differences between photon and proton therapy. Contouring was performed on both CTs, and plans (n=40 plans) and dose volume histograms were generated.
The mean GTV volume decreased 53.4% with re-simulation. All plans provided comparable PTV coverage. Compared with IMRT, adaptive IMRT significantly reduced the maximum dose to the mandible (p=0.020) and mean doses to the contralateral parotid gland (p=0.049) and larynx (p=0.049). Compared with IMRT and adaptive IMRT, IMPT significantly lower the maximum doses to the spinal cord (p<0.002 for both) and brainstem (p<0.002 for both) and mean doses to the larynx (p<0.002 for both) and ipsilateral (p=0.004 IMRT, p=0.050 adaptive) and contralateral (p<0.002 IMRT, p=0.010 adaptive) parotid glands. Adaptive IMPT significantly reduced doses to all critical structures compared with IMRT and adaptive IMRT and several critical structures compared with non-adaptive IMPT.
Although adaptive IMRT reduced dose to several normal structures compared with standard IMRT, non-adaptive proton therapy had a more favorable dosimetric profile than IMRT or adaptive IMRT and may obviate the need for adaptive planning. Protons allowed significant sparing of the spinal cord, parotid glands, larynx, and brainstem and should be considered for SCCHN to decrease normal tissue toxicity while still providing optimal tumor coverage.
head and neck cancer; proton therapy; adaptive radiotherapy; IMRT; treatment planning
Myoepithelial carcinoma is a rare malignancy of the parotid gland that is usually seen in adults. We report the first case in children of myoepithelial carcinoma of the parotid gland with massive invasion of the facial nerve and metastasis to cervical lymph nodes. Due to its rarity, the treatment and the clinical course of this tumor are not well defined yet. We performed a total parotidectomy, a modified neck dissection, and a postoperative radiotherapy in 7-year-old boy. Sparing of the facial nerve was impossible; it was sacrificed and grafted with a sural nerve. Histopathology confirmed the diagnosis of a parotid gland carcinoma and immunohistochemical markers showed that the tumor cells express cytokeratin, epithelial membrane antigen, cytokeratin 7, smooth muscle actin, P63, CEA, and S100. This pattern of immunostaining is consistent with the diagnosis of myoepithelial carcinoma. On the postoperative tenth month he presented with a pulmonary and lumbar vertebra metastasis.
Local control in malignant salivary gland tumours is dose dependent. High local control rates in adenoid cystic carcinomas could be achieved by highly conformal radiotherapy techniques and particle (neutron/carbon ion) therapy. Considering high doses are needed to achieve local control, all malignant salivary gland tumours probably profit from the use of particle therapy, which in case of carbon ion treatment, has been shown to be accompanied by only mild side-effects.
The COSMIC trial is a prospective, mono-centric, phase II trial evaluating toxicity (primary endpoint: mucositis ≥ CTCAE°3) and efficacy (secondary endpoint: local control, disease-free survival) in the combined treatment with IMRT and carbon ion boost in 54 patients with histologically proved (≥R1-resected, inoperable or Pn+) salivary gland malignancies. Patients receive 24 GyE carbon ions (8 fractions) and IMRT (50 Gy at 2.0 Gy/fraction).
The primary objective of COSMIC is to evaluate toxicity and feasibility of the proposed treatment in all salivary gland malignancies.
Clinical trial identifier NCT 01154270
The severe reduction of salivary function (xerostomia) is a common complication following radiation therapy for head and neck cancer. Consequently, guidelines to ensure adequate function based on parotid gland tolerance dose-volume parameters have been suggested by the QUANTEC group (1) and by Ortholan et al. (2). We perform a validation test of these guidelines against a prospectively collected dataset and compared to a previously published dataset.
Method and Materials
Whole-mouth stimulated salivary flow data from 66 head and neck cancer patients treated with radiotherapy at the British Columbia Cancer Agency (BCCA) were measured, and treatment planning data were abstracted. Flow measurements were collected from 50 patients at 3 months, and 60 patients at 12 month follow-up. Previously published data from a second institution (WUSTL) were used for comparison. A logistic model was used to describe the incidence of grade 4 xerostomia as a function of the mean dose of the spared parotid gland. The rate of correctly predicting the lack of xerostomia (negative predictive value, NPV) was computed for both the QUANTEC constraints and Ortholan et al. (2) recommendation to constrain the total volume of both glands receiving more than 40 Gy to less than 33%.
Both data sets showed a rate of xerostomia < 20 % when the mean dose to the least-irradiated parotid gland is kept below 20 Gy. Logistic model parameters for the incidence of xerostomia at 12 months after therapy, based on the least-irradiated gland, were D50=32.4 Gy and and γ=0.97. NPVs for QUANTEC guideline were 94% (BCCA data), 90% (WUSTL data). For Ortholan et al. (2) guideline NPVs were 85% (BCCA), and 86% (WUSTL).
This confirms that the QUANTEC guideline effectively avoids xerostomia, and this is somewhat more effective than constraints on the volume receiving more than 40 Gy.
radiotherapy; xerostomia; parotid gland; head and neck cancer; dose-volume effects