Evaluation of Xerostomia in Patients with Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy

Background: The sixth most prevalent cancer in the world is head and neck squamous cell carcinoma (HNSCC). In multiple combinations, surgery, radiation and chemotherapy are used in HNC control. As radiation-induced salivary gland damage and xerostomia is one of the most usual and distressing impacts, diffusion-weighted magnetic resonance imaging (DW-MRI) is a promising technique for the assessment of alterations due to radiation therapy. The aim of the study is to evaluate the effect of Chemoradiotherapy either concurrent or sequential/RTH on salivary glands using DW-MRI performed before and after chemoradiotherapy/RTH, correlation between DW-MRI changes and delivered radiation dose to salivary glands, study the acute toxicity of chemoradiotherapy/RTH on salivary glands and assess quality of life for patients with radiation-induced xerostomia. Patients and Methods: This prospective study included 43 patients with Head and Neck squamous cell carcinoma treated with definitive radiotherapy, sequential therapy or concurrent chemoradiotherapy at Clinical Oncology and Nuclear Medicine Department, MRI diffusion scans were done at Diagnostic Radiology Department Tanta University Hospitals throughout the period from May 2016 to May 2019. DW-MRI performed before and after RTH. For patients receiving CCRTH, DW sequence will be performed before starting RTH and 2 3 months post-RTH once at rest and then repeated continuously during salivary stimulation by ascorbic acid. In case of induction chemotherapy, DW-MRI was done before and after induction and 2 3 months post-RTH. Results: In all time periods, ADC values were lower for the PG than the SMG. ADC change of PGs was higher in hypopharyngeal carcinoma, while ADC change of SMGs How to cite this paper: Mansy, A.H., Salama, A.A., Khair-Allah, F.G. and El-Aziz, L.M.A. (2020) Evaluation of Xerostomia in Patients with Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy. Journal of Cancer Therapy, 11, 98-114. https://doi.org/10.4236/jct.2020.112009 Received: January 12, 2020 Accepted: February 25, 2020 Published: February 28, 2020 Copyright © 2020 by author(s) and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution-NonCommercial International License (CC BY-NC 4.0). http://creativecommons.org/licenses/by-nc/4.0/ Open Access DOI: 10.4236/jct.2020.112009 Feb. 28, 2020 98 Journal of Cancer Therapy


Background
Squamous cell carcinoma of the head and neck (HNSCC) is the world's sixth most common cancer [1].
For early stage HNSCC, patient achieved complete response when either treated with either surgery or radiotherapy. While, locally advanced HNSCC requires aggressive multimodality therapy incorporating local and systemic therapy with either chemotherapy and/or targeted therapy [2].
Although many patients are being cured of their disease, a significant percentage of survivors are suffering from the adverse effects associated with treatment.
Head and neck cancer and its treatment may affect the quality of life related to disease specific health (e.g., salivary and swallowing functions) [3].
Damage to the salivary gland and xerostomia caused by radiation is one of the most prevalent and distressing adverse effects. xerostomia is probably caused by several pronounced variables, such as radiation dose distribution, demographics, tumors and variables linked to treatment [4].
The extent of the dysfunction is associated with the dose and the volume of salivary tissue irradiated [5].
Minimal dysfunction of the gland can be noted at mean doses of 10 to 15 Gy and mean doses of >40 Gy to the parotid can lead to a decrease in function of 75 percent, the dysfunction at doses >54 Gy is regarded irreversible [6].
It is of great importance to early detect and prevent xerostomia. Thus far, salivary gland scintigraphy (SGS) and quantitative salivary flow rate measurements have been the cornerstone of evaluating salivary gland function in HNC patients SGS has been shown to be viable for anticipating salivary gland function after radiation therapy (RTH), but the usefulness of this method of measurement is restricted by its invasiveness and the radiation exposure associated with it [7].
In patients with HNSCC, a diffusion-weighted MRI (DWI) is frequently done.
Even during the early phases of the disease, the parameters of the apparent diffusion coefficient (ADC) may represent tissue microstructures or path physiological circumstances. Certainly, the ADC values could represent salivary gland function and xerostomia following RTH [8].

Aim
Study the effect of chemoradiotherapy either concurrent or sequential/RTH on salivary glands using DW-MRI performed before and after chemoradiotherapy/RTH, correlation between DW-MRI changes and delivered radiation dose to salivary glands, study the acute toxicity of chemoradiotherapy/RTH on salivary glands and assess quality of life for patients with radiation induced xerostomia.  For all examinations, a spine and neck coil head coil combined with a phased array was used. TR/TE = 5000/105 ms, in-plane pixel size = 2 × 2 mm, and b values = 0, 500 and 1000 s/mm 2 (three averages) were echo planar images parameters.

Assessment of Common Toxicity
Any adverse events were recorded. Chemotherapy toxicity grading was based on the common terminology criteria for adverse event ((NCI-CTC 5.0) [10]. acute and late toxicity criteria of the Radiation Therapy Oncology Group (RTOG) were used for grading radiotherapy toxicity [11].

Assessment of Quality of Life Related Xerostomia
Quality of life related xerostomia was based on (XQ of University of Michigan & QoL questionnaire by Dirix et al. [12].

Statistical Analysis
IBM SPSS Statistics software package version 21 was used for data analysis. Quantitative data was expressed using range, mean and standard deviation while Qualitative data was expressed in frequency and percent. Qualitative data was analyzed using Monte Carlo test. p-value was assumed to be significant at 0.05 [13].

Results
Age ranged from 40 to 70 years with mean age was 56 years with SD + 9.2, 50% were males and 48.8% were smokers.
Twenty six patients presented with laryngeal carcinoma (60.5%) from whom fifteen patients were glottic & eleven patients were supraglottic, while 23.3% presented with oropharyngeal carcinoma and 13.2% presented with hypopharyngeal carcinoma. Most patients were of performance 0/1. Patients' characteristics were shown in Table 1.
There was significant increase in ADC values for parotid glands post RTH post stimulation and this was also significant in pre-stimulation as shown in Table 2 & as regard submandibular glands, it was also the same as shown in Table   3 and Figure 1 & Figure 2.
As regard sequential group, there was an increase of ADC value post stimulation post-CTH for all ROI of parotid gland, but this increase was not significant DOI: 10.4236/jct.2020.112009 except for LT lower lobe as shown in Table 4 & as regard SMG, it was the same but the increase was not significant as shown in Table 5.         Table 2, and it was the same as regard LT parotid and LT SMG as shown in Table 3.
ADC change was statistically significant with site, stage and treatment modality, so high grade xerostomia was noticed in patients with locally advanced HNSCC treated with sequential therapy as shown in Table 7,
Xerostomia related quality of life scale questionnaire (15 questions), the answer of each question were as follows: 1, 2, 3, 4, 5: defined as not at all, a little, moderately, quite a lot; and very much respectively. It was ranged between 15 -75. The higher the score was, the worse the quality of life.
Patients who had xerostomia with low quality of life, and high quality were reported in 10 patients (76.9%), 3 patients (23%). respectively however, low quality of life was reported in one patient (14.3%) and high quality in 6 patients (85.7%) in patients with no xerostomia. among HNSCC receiving RTH statistical significant association between quality of life and xerostomia (p = 0.028*) as shown in Table 9.
Case 1 ( Figure 3): Male patient aged 65 years old presented with supraglottic with pyriform sinus extension SCC T2N2 M0 was treated with sequential therapy.
Case 2 ( Figure 4): Male patient aged 53 years old presented with glottic SCC T2N0 M0 was treated with definitive radiotherapy.

Discussion
In all head and neck cancers, multidisciplinary strategy should be used, the treatment choice for head and neck cancers is based on the site or extension of the primary tumor [2]. In different combinations, surgery, radiation, and chemotherapy are used to manage HNC. Early-stage disease (stage I and stage II) is generally handled with surgery or radiation alone. Treatment involves platinum-based chemo radiation, with or without induction chemotherapy (IC) as a sequential therapy for most patients with locally advanced disease (stage III and IVA/B [2]). ble results to surgery and radiotherapy but at the expense of side effects. However, parotid (PG) and Submandibular gland toxicity leads to loss of gland function [14].
Xerostomia is the most prominent complication in patients with head and neck carcinoma after radiotherapy (RTH) because radiation fields often involve bilaterally salivary glands, which are particularly radiosensitive [15].
Radiation-induced xerostomia is usually followed by impaired saliva processing and consequent co-morbidities such as oral infections, dental caries, loss of taste and dysphagia, which considerably decrease the quality of life of long-term RTH survivor [15].
It is proposed that diffusion-weighted magnetic resonance imaging (DW-MRI) is a promising procedure for evaluating changes due to radiotherapy. Our objective was to define the impact of RT/CRT on salivary gland before and after treatment s using DW-MRI [15].  [17].
Cross-tabulation between xerostomia on the quality of life among head and neck cancer patients undergoing radiotherapy showed p = 0.028 means that there was a significant relationship between xerostomia and quality of life.

Conclusions
Diffusion weighted MRI is a non-invasive procedure for evaluating the function of the salivary gland in patients with radiation-induced xerostomia. Xerostomia was significantly related to the quality of life. Xerostomia questionnaire is a useful tool for assessment of quality of life for patients with radiation induced xerostomia.

B Recommendation
 Submandibular gland sparing can reduce the risk of xerostomia.
 New modalities of radiotherapy are suggested, such as IMRT, IT has an important and efficient role in decreasing doses to salivary glands and consequently xerostomia decreases.  A comparative study is recommended between sequential or CCRTH with IMRT versus 3D conformal definitive RTH with evaluation of xerostomia.  Large sample size is recommended for better evaluation of xerostomia.