Palliative hypofractionated radiation therapy in incurable head-and-neck cancer patients – 2-year follow-up experience from a tertiary center from South India

S Kanmani Velarasan; Deivanayagam Ramasundaram

doi:10.4103/jrcr.jrcr_53_21

ORIGINAL ARTICLE

Year : 2022 | Volume : 13 | Issue : 2 | Page : 60-64

Palliative hypofractionated radiation therapy in incurable head-and-neck cancer patients – 2-year follow-up experience from a tertiary center from South India

S Kanmani Velarasan, Deivanayagam Ramasundaram
Department of Radiation Oncology, Regional Cancer Center, Tirunelveli Medical College, Tirunelveli, Tamil Nadu, India

Date of Submission	16-Nov-2021
Date of Decision	19-Nov-2021
Date of Acceptance	10-Feb-2022
Date of Web Publication	25-May-2022

Correspondence Address:
Dr. S Kanmani Velarasan
Department of Radiation Oncology, Regional Cancer Center, Tirunelveli Medical College, Tirunelveli, Tamil Nadu
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jrcr.jrcr_53_21

Abstract

Purpose: The main aim of the study was to assess tumor response to hypofractionated (HYPO Trial schedule) course of radiotherapy in patients with incurable squamous cell carcinoma of the head and neck in our patients. Materials and Methods: We retrospectively reviewed records of 23 patients treated between January 2019 and December 2019 with hypofractionated radiation therapy. These patients were given palliative radiation if they were deemed to be unsuitable for curative treatment due to poor general condition, comorbidities, advanced stage of disease, and/or advanced age. Radiation therapy schedule was 30 Gy in 5 fractions twice weekly and all the patients were treated with telecobalt machine. The assessment was done clinically. Records of tumor response, mucosal, and skin toxicity noted during radiation therapy and during follow-up were taken from patient records. Results: The most common primary site was oral cavity (48%) followed by oropharynx (31%). Most of the patients presented in Stage IVA (52%) followed by Stage III (31%) at diagnosis. Grades 2 and 3 mucositides were reported in 14 (64%) and 8 (36%), respectively. Eighty percent of the patients had partial response in primary and 65% of the patients had partial response in node. Twenty-seven percent of our patients had stable diseases. Partial response was seen in highest in patients with primary in oral cavity (80%) patients followed by hypopharynx (75%). Conclusion: This regimen offers better symptom palliation, acceptable treatment toxicity and appears practical in centers having a significant proportion of incurable head-and-neck cancer patients.

Keywords: Head and neck cancers, hypofraction, India, palliation, palliative chemotherapy, quality of life, radiotherapy

How to cite this article:
Velarasan S K, Ramasundaram D. Palliative hypofractionated radiation therapy in incurable head-and-neck cancer patients – 2-year follow-up experience from a tertiary center from South India. J Radiat Cancer Res 2022;13:60-4

How to cite this URL:
Velarasan S K, Ramasundaram D. Palliative hypofractionated radiation therapy in incurable head-and-neck cancer patients – 2-year follow-up experience from a tertiary center from South India. J Radiat Cancer Res [serial online] 2022 [cited 2023 Jun 7];13:60-4. Available from: https://www.journalrcr.org/text.asp?2022/13/2/60/346044

Introduction

Head-and-neck cancers form the sixth most common cancer globally.^[1] Lip and oral cavity cancers are the most common among head-and-neck cancers in terms of incidence and mortality according to the GLOBOCAN 2020. Head-and-neck cancers account for one-fourth of the total cancer patients in India. Oral cancers form around 40% to70% of head-and-neck cancer patients.^[2] Lip and oral cavity cancers stand next only to breast cancers in terms of incidence in India. In terms of mortality, lip and oral cancers stand next to breast and cervix cancers in India. The incidence of lip cancer and oral cancer occurs in an age group higher than 60 years.^[3] Men are more commonly affected than females. According to the Indian council of medical research statistics in 2018, the 5-year survival rate for early and advanced oral cavity cancer is around 82% and 27% in India.

Tobacco use, alcohol, and human papillomavirus infection are documented risk factors for head-and-neck cancers. Tobacco consumption is more among males and more common in rural areas. Epidemiology and presentation of head-and-neck cancer patients appear to be different in developed and developing countries.^[3]

Advanced squamous cell carcinoma of the head and neck carries a poor prognosis. Patients with locally advanced stages form a significant proportion in developing countries, particularly oral cavity.^[2] Patients usually die of uncontrolled locoregional disease. The 5-year survival even with aggressive treatment is <20%, with a median survival of fewer than 12 months. In most of these patients, curative treatment is not possible due to extensive locoregional disease, poor performance status, poor nutritional status, weight loss, comorbid conditions,^[4] and prior extensive surgery or radiation therapy.^[1]

There are significant scientific advances for patients with curable intent. Curative intent of treatment in this set of patients has shown to have significant toxicity related to treatment. It also increased the workload of radiation therapy machines in less developed countries.^[1] Best supportive care alone is associated with a median survival of 3 to 4 months in advanced squamous cell carcinoma of head-and-neck cancer patients.

Palliating symptoms with radiation dates back for more than a century. Radiation therapy can relieve symptoms secondary to primary as well as metastatic disease.^[5] Palliative radiation therapy regimens are significant in less developed countries. It can provide minimal treatment toxicity, reducing workload, and palliative symptoms at the earliest.^[4] Unfortunately, there is no high-level evidence to guide the optimal palliative regimen.^[1]

There is a lack of literature regarding the actual benefit and its applicability in the Indian scenario. Therefore, we decided to describe the tumor response and pattern of acute toxicities among adult patients diagnosed with incurable squamous cell carcinoma of the head and neck who underwent treatment with hypofractionated radiotherapy (HYPO Trial) schedule at our department.

Materials and Methods

We conducted a cross-sectional study of patients who underwent “HYPO trial” schedule in our department of radiation oncology at our medical college. Twenty-three patient records were identified between January 2019 and December 2019. Our common palliative radiation therapy schedule in practice was 30 Gy in 10 fractions given 5 days a week. Hence, there is a low number of patients for “HYPO trial” schedule group of patients.

“HYPO trial” schedule was delivering 30 Gy in 5 fractions two times in a week. Off-cord was done at 24 Gy. The treatment volume included the gross disease (either primary or nodal disease or both) alone. Manual marking was done. Around 1–1.5 cm margin was given to the gross disease as target volume. All the patients were treated with telecobalt machine.

Records of assessment of tumor response, skin, and mucosal toxicity were noted from patient records. Assessment of tumor response was done clinically. Acute skin and mucosal toxicity were measured using radiation therapy oncology group criteria.

Patients were given analgesics and feeding support if needed. Posttreatment, patients were generally followed up in monthly intervals for toxicity and symptom response. Information was retrieved from outpatient notes during follow-up visits.

Study population

Palliative radiotherapy (PRT) was given for patients presenting with head-and-neck cancers (squamous cell carcinoma histology and squamous cell carcinoma of unknown primary with neck nodes) who were deemed unsuitable for curative treatment and/or surgically unresectable disease due to poor general condition, comorbidities, advanced stage of disease, and/or advanced age.

Patient records with primary carcinoma nasopharynx, salivary gland primary, cutaneous squamous cell carcinoma, patients with the Eastern Cooperative Oncology Group (ECOG) 4 performance status, those with a previous history of radiotherapy to the head and neck, and those who underwent conventional treatment and other palliative schedules were excluded.

Study procedure

We retrospectively reviewed records of 23 patients who were treated with “HYPO trial” schedule between January 2019 and December 2019. A data extraction form was designed to collect data from the medical records maintained at the Department of Radiation Oncology. The data were collected by the principal investigator. The data abstraction form consisted of unique patient identifier, demographic characteristics (age, gender), clinical characteristics (tumor site, performance status, site-wise stage of the disease, and Tumor, Nodes, Metastases (TNM) seventh edition staging), treatment response (dose received, treatment duration, response in primary, response in nodal disease, and overall response), and treatment toxicities.

Plan of data entry and statistical analysis

We entered the data in Microsoft Excel sheet. Continuous variables such as the age of the patient, duration of treatment, and duration of survival were represented as mean (standard deviation) or median (interquartile range). Categorical variables such as tumor site, performance status, staging, response in primary, nodal disease, and overall response were represented as numbers and percentages. A univariate analysis was planned with a statistical significance of 0.05, however, owing to the small sample size, it could not be done.

Results

Twenty patients (87%) were males and 3 (13%) were females. Mean age of the patients was 62.5 years. Seven (30%) patients were above 70 years. Five (21%) of the patients were below 50 years. Only one patient had ECOG 3. Twelve (53%) patients had ECOG 1. Ten (43%) patients had ECOG 2. Squamous cell carcinoma was reported in biopsies of all the patients. The most common presenting symptoms were localized pain, odynophagia, difficulty in opening the mouth, skin ulceration, and dysphagia. Patient characteristics are shown in [Table 1].

Table 1: Demographic and clinical characteristics of patients who underwent hypofractionated radiotherapy for incurable head and neck carcinoma in a tertiary care hospital in South India between April 2019 and October 2019 (n=23)

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The most common primary site was in oral cavity for 11 (48%) patients, followed by oropharynx 7 (31%) patients, hypopharynx 4 (16%) patients, and larynx 1 (4%) patient. Most of the patients presented Stage IVA (52%), followed by Stage III (31%) and Stage IV B (17%) at diagnosis. Among patients with oral cavity site as subsite, 7 out of 11 patients presented in T4a and 3 out of 11 patients presented in T4b.

Nine out of 23 patients presented with N3 disease. Among those nine patients, oropharynx primary forms majority (44%). Site-wise and stage-wise characteristics were given in [Table 2].

Table 2: Site-wise tumor characteristics

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Prescription dose was 30 Gy in 19 (83%) patients and 36 Gy in 3 (13%) patients. One patient did not complete full treatment. Her general condition deteriorated after the first fraction and she discontinued further treatment. Concurrent chemotherapy was not administered in any of the patients.

Treatment toxicity

Grades 2 and 3 mucositides were reported in 14 (64%) and 8 (36%), respectively. Grades 0, 1, and 2 skin reaction were observed in 8 (36%), 13 (59%), and 1 (4%) patients. One patient developed orocutaneous fistula during the end of the treatment course. Twenty (87%) patients completed treatment (without treatment interruption) within 18 days. Only 2 (9%) patients completed treatment with interruption (range 21–23 days). Treatment break was due to Grade 3 mucositis. There were no treatment or tumor-related deaths during the treatment course.

Treatment response

Around 73% of the patients had partial response either in primary or node or both [details given in [Table 3]]. Twenty-seven percent of our patients had stable disease. Partial response was seen in highest in patients with primary in oral cavity (80%) patients followed by hypopharynx (75%). Three patients developed disease progression during follow-up visits. Most of the patients did not come for follow-up visits regularly. Few patients were started on metronomic chemotherapy (tablet methotrexate 10 mg weekly). The mean follow-up was 8 months (range 5–24 months).

Table 3: Treatment characteristics

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By the time of this analysis, 22 (96%) patients had died. Only 1 (4%) patient lived beyond 24 months following treatment.

Discussion

In India, around 66% of patients with squamous cell carcinoma of the head-and-neck cancers present in locally advanced stages.^[6] Head-and-neck cancer patients have unacceptably high mortality rates in less developed countries.^[7] The gingivobuccal region is most commonly involved.^[8] Most of the time, these patients are unfit for surgery and systemic chemotherapy. There are only little treatment options available for these patients. Poor compliance to therapy, limited enrolment in prospective trials, and high loss to follow-ups rates make outcome assessment difficult and challenging in this population.

Palliative radiation therapy regimens are aimed at improving quality of life (QOL). Radiation therapy with palliative intent plays a significant role in symptom palliation. However, there is little guidance or no consensus available for oncologists to decide on an optimal regimen. Treatment schedules in the literature included ranging from conventional to stereotactic radiation therapy techniques, duration ranging between 1 and 7 weeks with varying response rates and toxicities. PRT provides effective palliation and improved QOL in advanced incurable malignancies. Palliative radiation schedules were also offered in cyclic and split courses. Nonradiation palliative treatment options available in the literature are surgery, systemic chemotherapy, metronomic chemotherapy, and immunotherapy. There are multiple palliative radiation therapy schedules available in the literature.

In Porceddu et al., 81% of the patients were males.^[5] The most common site was the oropharynx (32%) followed by the oral cavity (27%). Patients commonly present in Stage IVA (38%) followed by Stage 2 (24%). The primary objective response was 74% and the nodal response was 63%. The overall response was seen in 80% of the patients.

In Corry et al., 14 Gy in 4 fractions were given twice in a day in cycles based on response.^[9] Males (73%) were predominant and the most common site was oral cavity (43%). Median age was 73 years. Fifty-three percent of patients received three cycles and 27% of the patients received two courses. Seventy-seven percent of the patients had a response for treatment. There was minimal treatment toxicity.

In Nguyen et al., 24 Gy was given in 8 Gy per fraction weekly once for consecutive 3 weeks.^[10] In this study, intensity-modulated radiation therapy technique was used for most patients. Around 61.8% of patients presented with Stage IV. Patients with performance status ECOG 3 were 38.2% around 80% of the patients had objective responses. Treatment was well tolerated. Overall survival was 6.2 months. Late toxicity was not able to review.

In Mohanti et al., 20 Gy in 5 fractions were given in a week.^[11] 78% of the patients were in Stage IVA. Clinical assessment for response was based on relation to one rupee coin. Symptom relief was seen in 55% of the patients. Progression of symptoms was seen in 24% of patients. The treatment schedule was well tolerated.

In Ghoshal et al., 30 Gy in 10 fractions were given over 2 weeks.^[12] 72% of the patients were in Stage IV. This schedule was well tolerated. No patients had Grade 3 mucositis. More than 50% symptom relief is seen in 90% of patients.

In Al-Mamgani et al., 50 Gy in 16 fractions were given over 3 weeks.^[13] Oropharynx (31%) was the most common site followed by oral cavity (23%) and hypopharynx (23%). Forty-two percent and 30% of patients were in Stage IVA and IVB, respectively. Grade 3 dermatitis and confluent mucositis were seen in 45% and 65% of the patients. There was no treatment break due to acute toxicity. The overall response rate was 73%. Response was highest in larynx primary (91%) and minimal in hypopharynx primary (61%). There was acceptable late toxicity.

In Das et al., 40 Gy in 10 fractions were given with 2 fractions per week.^[4] Sixty-one percent of the patients were in Stage IVB. Grade 3 mucositis and dermatitis were seen in 18% and 3% of the patients. QOL was assessed prospectively using questionnaire. There was an improvement in all aspects of QOL. Median survival was 7 months.

In Minatel et al., two courses of radiotherapy were given.^[14] Each course had 25 Gy in 10 fractions over 2 weeks with 2-week break in between. Concurrent bleomycin 10 mg was given twice a week along with radiotherapy. The complete response was seen in 28% and partial response was seen in 41% of the patients. Forty-three percent of the patients had Grade 3 stomatitis. Median overall survival was 7 months.

In Jakhar et al. (OCTA-SHOT), 28 Gy/8 fractions/4 days, 3.5 Gy were delivered per fraction (two such fractions in a day) in a week continuously.^[15] Sixty-four percent of the patients had more than 50% of response. Nine percent of the patients had Grade 3 mucositis. Eighty-two percent of the patients had Grade 2 dermatitis.

From the above studies, males form higher percentage. Most of the patients had median age above 65 years. Oral cavity dominates the subsite in Indian studies. Most of the patients presented at Stage IVA and IVB. In most of the above studies, the response rate was above 70%. Significant number of patients completed treatment without breaks. Our study also had similar findings.

Those patients with ECOG 3, 8 Gy weekly for 3 weeks can be offered as in Nguyen et al. This regimen reduces workload and appears simple. Only concern is intensity-modulated radiation therapy technique was used in this study. Conformal techniques may not be available in all Indian centers.

Problems in this cohort of patients are very low number of patients came for follow-ups. Hence, there is difficulty in documentation of durable response. Durability of response is an important parameter in the treatment of these patients. Poor performance status is an important predictor of outcome.

Selection of regimen should be based on holistic assessment. There are several tools or nomograms available for prognostication. However, they require validation. This cohort of patients requires personalized treatment based on their goals of life. Choice of regimen should be based on prognosis, goals of care, and other palliative treatment options.

Conclusion

In our center, we observed that “HYPO trial” schedule provided symptom relief, patients completed treatment within scheduled time and acceptable mucosal and skin toxicities. This regimen appears practical in centers having a significant proportion of incurable head-and-neck cancer patients. It saved patient's precious time and decreased workload in treatment machines.

Limitations

This is a retrospective review of records. Details regarding mucosal toxicity and skin toxicities during follow-ups were not able to retrieve. Most of the patients did not turn up for follow-up after few visits. Their wellness was enquired through phone. Details about the death of patients were not retrieved as most of the deaths were in their homes. QOL assessment was not assessed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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