|Year : 2019 | Volume
| Issue : 3 | Page : 528-532
Role of hypofractionated palliative radiotherapy in patients with stage four head-and-neck squamous cell carcinoma
Ankur Mudgal, Ashok Kumar Arya, Indira Yadav, Sandeep Chaudhary
Department of Radiotherapy, Sarojini Naidu Medical College, Agra, Uttar Pradesh, India
|Date of Web Publication||29-May-2019|
Dr. Ashok Kumar Arya
Department of Radiotherapy, Sarojini Naidu Medical College, Agra, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
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 2020 Jan 26];15:528-32. Available from: http://www.cancerjournal.net/text.asp?2019/15/3/528/244436
| > Introduction|| |
Head-and-neck squamous cell carcinoma (HNSCC) is one of the most commonly found cancers in the world. With 77,000 new cases diagnosed per year, HNSCC is the second-most common cancer in the Indian population., 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. Hypofractionated radiotherapy decreases overall treatment time and increases dose per fraction has radiobiological advantage over conventional protocol.,, 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|| |
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.
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. 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., 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.
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|| |
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%).
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).
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.
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.
| > Discussion|| |
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. In these cases, surgical resection is not preferred as there are chances of incomplete resections. Chemotherapy is considered in patients with widespread metastases. The short course of palliative radiotherapy has provided good symptomatic relief and high tumor response rates.,,
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., 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.
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. 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. 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. 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. Various hypofractionated regimens were compared in [Table 5].,,,,,,,,,,,,
|Table 5 : Comparison of various hypofractionated palliative radiotherapy regimens|
Click here to view
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|| |
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
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Grégoire V, Lefebvre JL, Licitra L, Felip E, EHNS-ESMO-ESTRO Guidelines Working Group. Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21 Suppl 5:v184-6.
Mayne ST, Morse DE, Winn DM. Cancers of the oral cavity and pharynx. In: Schottenfeld D, Fraumeni FJ, editors. Cancer Epidemiology and Prevention. 3rd
ed. New York, USA: Oxford University Press; 2006. p. 674-96.
Talapatra K, Gupta T, Agarwal JP, Ghosh-Laskar S, Srivastava S, Dinshaw K. Palliative radiotherapy in head and neck cancers: Evidence based review. Indian J Palliat Care 2006;12:44-50. [Full text]
Soni A, Kaushal V, Verma M, Dhull AK, Atri R, Dhankhar R, et al.
Comparative evaluation of three palliative radiotherapy schedules in locally advanced head and neck cancer. World J Oncol 2017;8:7-14.
Murthy V, Kumar DP, Budrukkar A, Gupta T, Ghosh-Laskar S, Agarwal J, et al.
Twice-weekly palliative radiotherapy for locally very advanced head and neck cancers. Indian J Cancer 2016;53:138-41.
] [Full text]
Kumar A, Sharma A, Mohanti BK, Thakar A, Shukla NK, Thulkar SP, et al.
A phase 2 randomized study to compare short course palliative radiotherapy with short course concurrent palliative chemotherapy plus radiotherapy in advanced and unresectable head and neck cancer. Radiother Oncol 2015;117:145-51.
Cox JD, Stetz J, Pajak TF. Toxicity criteria of the radiation therapy oncology group (RTOG) and the european organization for research and treatment of cancer (EORTC) Int J Radiat Oncol Biol Phys 1995;31:1341-6.
Hassan SJ, Weymuller EA Jr. Assessment of quality of life in head and neck cancer patients. Head Neck 1993;15:485-96.
Rogers SN, Gwanne S, Lowe D, Humphris G, Yueh B, Weymuller EA Jr., et al.
The addition of mood and anxiety domains to the university of Washington quality of life scale. Head Neck 2002;24:521-9.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al.
New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47.
Kancherla KN, Oksuz DC, Prestwich RJ, Fosker C, Dyker KE, Coyle CC, et al.
The role of split-course hypofractionated palliative radiotherapy in head and neck cancer. Clin Oncol (R Coll Radiol) 2011;23:141-8.
Colevas AD. Chemotherapy options for patients with metastatic or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol 2006;24:2644-52.
Bentzen SM, Saunders MI, Dische S, Bond SJ. Radiotherapy-related early morbidity in head and neck cancer: Quantitative clinical radiobiology as deduced from the CHART trial. Radiother Oncol 2001;60:123-35.
Weissberg JB, Pillsbury H, Sasaki CT, Son YH, Fischer JJ. High fractional dose irradiation of advanced head and neck cancer. Implications for combined radiotherapy and surgery. Arch Otolaryngol 1983;109:98-102.
Das S, Thomas S, Pal SK, Isiah R, John S. Hypofractionated palliative radiotherapy in locally advanced inoperable head and neck cancer: CMC Vellore experience. Indian J Palliat Care 2013;19:93-8.
] [Full text]
Radiotherapy Dose Fractionation. Board of Faculty of Clinical Oncology, Royal College of Radiology. London: Royal College of Radiologists; 2006. p. 40-3.
Mohanti BK, Umapathy H, Bahadur S, Thakar A, Pathy S. Short course palliative radiotherapy of 20 gy in 5 fractions for advanced and incurable head and neck cancer: AIIMS study. Radiother Oncol 2004;71:275-80.
Paris KJ, Spanos WJ Jr. Lindberg RD, Jose B, Albrink F. Phase I-II study of multiple daily fractions for palliation of advanced head and neck malignancies. Int J Radiat Oncol Biol Phys 1993;25:657-60.
Erkal HS, Mendenhall WM, Amdur RJ, Villaret DB, Stringer SP. Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head and neck mucosal site treated with radiation therapy with palliative intent. Radiother Oncol 2001;59:319-21.
Ghoshal S, Patel F, Mudgil N, Bansal M, Sharma S. Palliative radiotherapy in locally advanced head and neck cancer-a prospective trial. Indian J Palliat Care 2004;10:19. [Full text]
Corry J, Peters LJ, Costa ID, Milner AD, Fawns H, Rischin D, et al.
The 'QUAD SHOT' – A phase II study of palliative radiotherapy for incurable head and neck cancer. Radiother Oncol 2005;77:137-42.
Porceddu SV, Rosser B, Burmeister BH, Jones M, Hickey B, Baumann K, et al.
Hypofractionated radiotherapy for the palliation of advanced head and neck cancer in patients unsuitable for curative treatment—”Hypo trial”. Radiother Oncol 2007;85:456-62.
Agarwal JP, Nemade B, Murthy V, Ghosh-Laskar S, Budrukkar A, Gupta T, et al.
Hypofractionated, palliative radiotherapy for advanced head and neck cancer. Radiother Oncol 2008;89:51-6.
Ghoshal S, Chakraborty S, Moudgil N, Kaur M, Patel FD. Quad shot: A short but effective schedule for palliative radiation for head and neck carcinoma. Indian J Palliat Care 2009;15:137.
] [Full text]
Paliwal R, Kumar-Patidar A, Walke R, Hirapara P, Jain S, Raj-Bardia M, et al.
Palliative hypo-fractionated radiotherapy in locally advanced head and neck cancer with fixed neck nodes. Iran J Cancer Prev 2012;5:178-82.
Jakhar SL, Purohit R, Solanki A, Murali P, Kothari T, Sharma N, et al.
Accelerated hypofractionation (OCTA SHOT): Palliative radiation schedule in advanced head and neck carcinoma. J Cancer Res Ther 2017;13:943-6.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]