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ORIGINAL ARTICLE
Year : 2019  |  Volume : 15  |  Issue : 3  |  Page : 528-532

Role of hypofractionated palliative radiotherapy in patients with stage four head-and-neck squamous cell carcinoma


Department of Radiotherapy, Sarojini Naidu Medical College, Agra, Uttar Pradesh, India

Date of Web Publication29-May-2019

Correspondence Address:
Dr. Ashok Kumar Arya
Department of Radiotherapy, Sarojini Naidu Medical College, Agra, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_116_18

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 > Abstract 


Background: Large number of patients with head-and-neck cancer presents with factors such as advanced disease, poor general condition, and associated comorbidities due to which radical treatment is not recommended in these patients. In this scenario, the aim of the present study is to assess the role and feasibility of hypofractionated palliative radiotherapy in these patients.
Subjects and Methods: This study was conducted on patients with histopathologically proven cases of squamous cell carcinoma of the head-and-neck region who were surgically unresectable. The quality of life (QOL) was assessed before and after 1 month of radiotherapy using University of Washington Quality of Life questionnaire version 4. All patients received 40 Gy in 10 fractions, twice weekly by two lateral fields covering primary and secondary disease. Response evaluation criteria in solid tumor criteria were used to assess the tumor response. Toxicity was assessed weekly using radiation therapy oncology group criteria.
Results: A total of 50 patients were enrolled in this study, out of which 46 completed the planned treatment of 40 Gy in 10 fractions. Common complaints were distressing pain at the primary site (42%), neck swelling (30%), difficult in swallowing (18%), and change in voice (10%). Statistically significant improvements were observed in overall QOL (26.9 ± 9.63 to 55.65 ± 19.28) and none of them experienced Grade IV mucositis or skin toxicity. Good objective response was seen in 82.6% and 84.7% of patients at primary and nodal sites, respectively.
Conclusions: This hypofractionated palliative radiotherapy regimen is a good treatment option in patients with Stage IV head-and-neck cancer, who are not fit for treatment with curative intent.

Keywords: Head and neck cancer, hypofractionated radiotherapy, pain control, palliative radiotherapy


How to cite this article:
Mudgal A, Arya AK, Yadav I, Chaudhary S. Role of hypofractionated palliative radiotherapy in patients with stage four head-and-neck squamous cell carcinoma. J Can Res Ther 2019;15:528-32

How to cite this URL:
Mudgal A, Arya AK, Yadav I, Chaudhary S. Role of hypofractionated palliative radiotherapy in patients with stage four head-and-neck squamous cell carcinoma. J Can Res Ther [serial online] 2019 [cited 2019 Aug 22];15:528-32. Available from: http://www.cancerjournal.net/text.asp?2019/15/3/528/244436




 > Introduction Top


Head-and-neck squamous cell carcinoma (HNSCC) is one of the most commonly found cancers in the world.[1] With 77,000 new cases diagnosed per year, HNSCC is the second-most common cancer in the Indian population.[2],[3] Advanced head-and-neck cancer carries poor prognosis and is often found unfit for radical surgical treatment or combined modality due to poor nutritional status.[4] Hypofractionated radiotherapy decreases overall treatment time and increases dose per fraction has radiobiological advantage over conventional protocol.[5],[6],[7] There is a deficit of guidelines in the current literature regarding appropriate palliative regimen due to poor compliance to therapy, less enrolment in prospective trials, and short duration of follow-up. Thus, we conducted a prospective study to quantify the response and radiation toxicity of short course palliative hypofractionated radiotherapy and assess the improvement of quality of life (QOL) in advanced head-and-neck cancer patients.


 > Subjects and Methods Top


This prospective cohort study was conducted on patients reported in radiotherapy department between October 2015 and September 2017. Approval of protocol was taken by the Institutional Review Board before carrying out the study. Patients and family were explained about the incurable stage of disease. Written informed consent was taken. Patients with unresectable Stage IV biopsy proven squamous cell carcinomas of the head-and-neck region were included in the study. Patient with nasopharyngeal, paranasal sinus, and salivary gland as primary were excluded from the study. Patients who have previously received treatment in the form of radiotherapy or chemotherapy were also excluded from the study.

Treatment plan

Distressing presenting symptoms such as pain, painful ulcer, dysphagia, odynophagia, breathing difficulty, and neck swelling were recorded. Analgesics were prescribed according to the World Health Organization analgesic ladder. Anxiolytics and antitussives were given for relief of insomnia and cough. External beam radiotherapy was delivered to a dose of 40 Gy in 10 fractions (Tuesday and Friday). The biologically equivalent dose for this regimen for tumor and late reacting tissue is 56 Gy10 and 93.3 Gy3, respectively. Patients were immobilized in supine position and head fixed with timo headrest. Primary and nodal gross tumor volumes were outlined based on clinical examination, indirect/direct laryngoscopy. Radiotherapy portal included gross tumor volume with 2-cm margin and the high-risk nodal regions. Bolus was used in cases of skin involvement. Radiotherapy was delivered by parallel opposed lateral technique in telecobalt machine (Theratron Phoenix). Patients with good response were further planned for radiotherapy with high palliative intent. Patients with progressive disease taken on tablet gefitinib 250 mg daily with injection methotrexate 50 mg weekly.

The primary objective was relief in distressing symptoms and enhancement in QOL, and the secondary objective was to evaluate tumor response, radiation-induced toxicity, and overall survival. All patients reviewed once weekly during radiotherapy to assess symptom relief and toxicity. Treatment-related toxicities such as mucositis and dermatitis were assessed using RTOG criteria.[8] QOL was assessed using the University of Washington Quality of Life (UWQOL) Questionnaire version 4.0 before and after 4 weeks of radiotherapy. It consists of 15 questions in which score 0 shows the least response and 100 shows the best response. The various domains are pain, activity, swallowing, appearance, recreation, chewing, shoulder, speech, saliva, taste, anxiety, and mood. The social domain score, physical domain score, health-related QOL in the past 7 days (HRQOL 7 days), and overall QOL were also assessed.[9],[10] The assessment of UWQOL questionnaire was done by treating doctor. Vernacular language was used for better understanding of patients. Tumor response was assessed using RECIST criteria.[11]

Statistical analysis

Statistical analysis was done with the help of IBM SPSS Statistics 22.0 software. Demographic profiles of patients, treatment parameters, and radiation-induced toxicity were analyzed using descriptive statistics. UWQOL questionnaire was evaluated using the paired t-test. P < 0.05 was considered as statistically significant. Kaplan–Meier survival analysis method was used to calculate median overall survival (OAS). OAS was calculated from the beginning of radiotherapy till death or last date of follow-up.


 > Results Top


A total of 50 patients were enrolled in the study. Out of which 46 patients completed the treatment as per protocol, four patients lost to follow-up after registration. Demographic profile of the patients is described in [Table 1]. Male preponderance (89.1%) was seen and the median age was 47 (24–77) years. The most common site was oral cavity 22 (47.8%) and most frequent complaint was of pain 40 (86.4%).
Table 1: Demographic profile of the patients

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All of these 46 patients completed treatment, and it seemed to be well tolerated. Grade III acute mucosal and skin toxicities were seen in 4 (8.6%) and 1 (2.17%) cases, respectively. There was no Grade IV mucosal or skin toxicity seen during the treatment. None of the patients died due to acute radiation toxicity. Three patients needed nasogastric tube feeding during radiation due to progressive difficulty in swallowing. About 84% of the patients completed the planned radiation therapy without any break during the treatment. Two patients were prescribed morphine for severe pain remaining patients had only mild-to-moderate pain. Four patients needed hospitalization during treatment.

Patients were assessed on the basis Karnofsky Performance Scale before radiation and 1 month after completion of treatment [Table 2]. There was significant improvement in mean score before and after radiation therapy (55.2 to 68.70, P < 0.001).
Table 2: Karnofsky performance status (KPS) of the patients

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Using UWQOL questionnaire version 4, the mean ± standard deviation scores of the individual questions, before and after radiation for patients, have been calculated and it is depicted in [Table 3]. In this study, significant (statistically) improvements were observed in scores of pain, activity, anxiety, appearance, mood, social domain score, physical domain score, HRQOL, and overall QOL (26.9 ± 9.63 to 55.65 ± 19.28, P = 0.000). Salivation and taste scores decreased significantly.
Table 3: Quality of life assessment

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Tumor response was recorded with the help of clinical examination, direct and indirect laryngoscopy; these results are shown in [Table 4]. In the posttreatment evaluation, three (6.5%) patients showed a complete response at primary and 6 (13%) at nodal site. Thirty-five (76.1%) and 33 (77.1%) patients showed partial response at primary and nodal sites, respectively. Eight (17.3%) and seven (15.2%) patients had stable disease at primary and nodal sites, respectively, 1 month after completion of radiotherapy. The median overall survival was 9 months. Four (8.6%) patients were still alive at the time of closure of the study.
Table 4: Tumor response

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 > Discussion Top


Most of the patients with HNSCC present in locally advanced stage which causes symptoms such as pain at the local site, difficulty in swallowing, chewing and mouth opening, change in voice, swelling over face, and bleeding and airway obstruction. Patients with Stage IV disease can only be treated using single modality due to low-performance status.[12] In these cases, surgical resection is not preferred as there are chances of incomplete resections. Chemotherapy is considered in patients with widespread metastases.[13] The short course of palliative radiotherapy has provided good symptomatic relief and high tumor response rates.[5],[6],[7]

Rationale behind using a hypofractionated radiotherapy schedule is to reduce overall treatment time which will allow treatment completion before accelerated repopulation and higher dose per fraction gives better control for hypoxic fraction of large tumors.[14],[15] Furthermore, machine time will be well utilized in the centers where there is excessive workload and is also beneficial for the patients coming from faraway places.[16]

Mohanti et al. treated 505 patients of Stage IV HNSCC with a dose of 20 Gy in five fractions over 1 week and got good symptomatic relief (50% or more) with median overall survival of 6 months.[17] Das et al. in his study used 40 Gy/10 fractions/twice weekly observed improvement in QOL (17.4 vs. 20.01), after treatment. Median overall survival of the group was 7 months.[18] Murthy et al. in his schedule of 32Gy/8 fractions/twice weekly obtained overall response rates of 42% at primary site and 55% at nodal site and 76.3% of the patients got relief in pain and 42.8% patients got improvement in depression and anxiety levels with minimal toxicity.[6] Soni et al. compared three fractionation schedules that are 14.8 Gy in four fractions over 2 days, repeated 3 weekly for two more cycles, 50 Gy in 16 fractions in 3.1 weeks and 20 Gy in five fractions over 1 week, repeated after an interval of 3 weeks. Local control rates were 84%, 76%, and 76%, respectively. Grade III mucositis was seen in 36%, 56%, and 24% of patients, respectively.[5] Various hypofractionated regimens were compared in [Table 5].[5],[6],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27]
Table 5 : Comparison of various hypofractionated palliative radiotherapy regimens

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The ten fractions twice-weekly schedule used in our study also showed similar results as seen in the above-mentioned studies. Statistically significant improvement is seen in overall QOL (26.9 ± 9.63 to 55.65 ± 19.28). After completion of treatment, good objective response was seen in 82.6% and 84.7% at tumor and nodal sites, respectively, with minimal toxicity.

The constraints with this trial are that it is a single arm study having less number of patients with short follow-up, which prevents its comparison with the conventional regimes.


 > Conclusions Top


This short course of radiotherapy has potential to achieve reasonably high dose at tumor site and thus produces good symptomatic relief with minimal toxicity in patients with locally advanced HNSCC. An optimal fractionation schedule for palliative radiotherapy in head-and-neck cancer is yet to evolve. The current evidence seems to favor this short course palliative radiotherapy schedule.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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