European Journal of Cardiovascular Medicine

Head and neck cancers (HNCs) represent a major global health burden and account for approximately 650,000 new cases and over 330,000 deaths annually worldwide. A significant proportion of patients present with locally advanced or metastatic disease, especially in developing countries such as India, where delayed diagnosis, limited access to healthcare, and socioeconomic factors contribute to advanced-stage presentation1. In such patients, the goals of treatment often shift from cure to symptom control, improvement of quality of life (QoL), and maintenance of functional status.¹

Patients with advanced head and neck cancer frequently suffer from debilitating symptoms including pain, dysphagia, bleeding, airway obstruction, foul odor, and ulceration, which severely impair physical, emotional, and social well-being. Conventional radical radiotherapy or chemoradiation may not be feasible in many cases due to poor performance status, extensive disease, prior treatment, or comorbidities. Therefore, palliative radiotherapy regimens play an important role in providing rapid symptom relief with minimal toxicity and shorter treatment duration.²

The Quad Shot radiotherapy regimen, originally developed at the Radiation Therapy Oncology Group (RTOG), is a hypofractionated palliative radiotherapy schedule consisting of 14 Gy delivered in four fractions over two consecutive days, typically repeated at 3–4 week intervals for up to three cycles depending on response and tolerance. This regimen is particularly attractive for patients with advanced disease because it offers short treatment time, good symptom palliation, acceptable toxicity profile, and minimal interruption of systemic therapy or supportive care2,3

Several studies have demonstrated that Quad Shot radiotherapy provides significant symptomatic relief, tumor response, and improvement in quality of life in patients with incurable head and neck cancers4,5. Response rates ranging from 50–80% have been reported, with meaningful improvements in pain control, swallowing ability, and bleeding. Moreover, the regimen is well tolerated even in frail patients, making it an effective option for palliative management.⁴

Despite increasing use of the Quad Shot regimen, there remains a need for prospective clinical studies evaluating both treatment response and patient-reported quality of life outcomes, particularly in resource-limited settings. Assessing QoL parameters alongside tumor response is essential in palliative oncology because the primary goal is to improve patient comfort and functional status rather than prolong survival alone5.

Therefore, the present study was undertaken to evaluate the effectiveness of Quad Shot radiotherapy in terms of tumor response and improvement in quality of life in patients with locally advanced or metastatic head and neck cancer.

Aim

To evaluate the quality of life and treatment response following Quad Shot radiotherapy in patients with locally advanced or metastatic head and neck cancer.

Objectives

1. To assess the tumor response after Quad Shot radiotherapy in patients with locally advanced or metastatic head and neck cancer.
2. To evaluate changes in quality of life parameters before and after treatment using standardized assessment tools.
3. To determine the symptomatic relief in common symptoms such as pain, dysphagia, bleeding, and airway obstruction following treatment.
4. To assess the treatment tolerance and acute toxicities associated with the Quad Shot radiotherapy regimen.

Study Design and Setting This was a prospective observational study conducted in the Department of Radiotherapy at a tertiary care teaching hospital. The study was carried out over a period of 18 months after obtaining approval from the Institutional Ethics Committee. Written informed consent was obtained from all participating patients prior to enrollment in the study. Study Population Patients diagnosed with locally advanced or metastatic head and neck cancer who were not suitable for curative treatment and were planned for palliative Quad Shot radiotherapy were included in the study. Inclusion Criteria 1. Histopathologically confirmed squamous cell carcinoma of the head and neck region. 2. Patients with locally advanced, recurrent, or metastatic disease not amenable to curative surgery or radical radiotherapy. 3. Age ≥18 years. 4. Eastern Cooperative Oncology Group (ECOG) performance status 0–3. 5. Patients willing to participate and provide informed consent. Exclusion Criteria 1. Patients who had previously received palliative radiotherapy to the same site within the last 6 months. 2. Patients with severe comorbid conditions preventing radiotherapy. 3. Patients with ECOG performance status >3. 4. Patients unwilling to participate in the study. Sample Size A total of 60 patients meeting the inclusion criteria were included in the study during the study period. Treatment Protocol All eligible patients received Quad Shot radiotherapy, which consisted of 14 Gy delivered in four fractions (3.5 Gy per fraction) over two consecutive days, with two fractions per day separated by an interval of at least 6 hours. The treatment cycle was repeated every 3–4 weeks for up to three cycles, depending on tumor response, symptom relief, and patient tolerance. Radiotherapy was delivered using external beam radiotherapy (EBRT) with either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) techniques, based on machine availability and tumor characteristics. Assessment of Treatment Response Tumor response was evaluated 4 weeks after completion of the first Quad Shot cycle and subsequently after additional cycles where applicable. Response assessment was performed using clinical examination and imaging studies where necessary. Tumor response was categorized according to RECIST criteria as: • Complete Response (CR) • Partial Response (PR) • Stable Disease (SD) • Progressive Disease (PD) Quality of Life Assessment Quality of life (QoL) was assessed using validated questionnaires such as: • EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) • EORTC QLQ-H&N35 (Head and Neck Cancer module) QoL evaluation was performed before initiation of treatment and after completion of radiotherapy cycles to assess improvement in symptoms such as pain, swallowing difficulty, speech problems, and social functioning. Assessment of Symptom Relief Symptom relief was evaluated for common symptoms including: • Pain • Dysphagia • Bleeding • Foul odor • Airway obstruction The severity of symptoms was graded using standard symptom scoring scales before and after treatment. Toxicity Assessment Treatment-related acute toxicities were recorded and graded according to the Radiation Therapy Oncology Group (RTOG) acute radiation morbidity scoring criteria. Statistical Analysis All collected data were entered into a structured database and analyzed using statistical software (SPSS version 22.0). Descriptive statistics were used to summarize demographic and clinical characteristics. Continuous variables were expressed as mean ± standard deviation, and categorical variables were presented as frequency and percentage. Changes in quality of life scores before and after treatment were analyzed using the paired t-test, and a p-value <0.05 was considered statistically significant.

During the study period of 18 months, a total of 60 patients with locally advanced or metastatic head and neck cancer were enrolled and treated with Quad Shot radiotherapy. The demographic characteristics, tumor response, quality of life improvement, and treatment-related toxicities were analyzed.

Table 1: Demographic and Clinical Characteristics of Patients (n = 60)

Most patients were males (70%), and the most common age group was 50–60 years (43.3%). The oral cavity (36.7%) was the most frequent primary tumor site.

Table 2: Tumor Response Following Quad Shot Radiotherapy

Overall objective response rate (CR + PR) was 60%, indicating significant tumor regression in a majority of patients following Quad Shot radiotherapy.

Table 3: Symptom Relief After Treatment

Significant symptomatic relief was observed following treatment, particularly in pain (71.1%) and bleeding (80%), contributing to improved patient comfort.

Table 4: Quality of Life (QoL) Improvement

There was a statistically significant improvement in overall quality of life following Quad Shot radiotherapy, with reduction in pain and swallowing difficulty and improvement in social functioning (p < 0.05).

Table 5: Treatment-Related Toxicity (RTOG Acute Toxicity)

Most patients experienced mild to moderate toxicity (Grade 1–2). Only 3.4% developed Grade 3 mucositis, and no Grade 4 toxicity was observed, indicating that the Quad Shot regimen was well tolerated.

Head and neck cancers are commonly diagnosed at an advanced stage, particularly in developing countries, where many patients present with locally advanced or metastatic disease. In such situations, curative treatment may not be feasible because of extensive tumor burden, poor performance status, or associated comorbidities. Therefore, palliative radiotherapy plays a critical role in symptom control and improvement of quality of life in these patients. The Quad Shot radiotherapy regimen, a hypofractionated schedule delivering radiation over a short period, has been increasingly used for this purpose.

In the present study, the majority of patients were males (70%), and the most common age group was 50–60 years. This demographic pattern is consistent with previous studies which report a higher prevalence of head and neck cancers among males due to higher exposure to risk factors such as tobacco chewing, smoking, and alcohol consumption. ⁶

The most common primary tumor site observed in our study was the oral cavity, followed by the oropharynx and larynx. Similar findings have been reported in several Indian studies where oral cavity cancers constitute a significant proportion of head and neck malignancies due to the widespread habit of tobacco and betel nut consumption7.

In our study, the overall objective response rate (complete response + partial response) was 60%, indicating that Quad Shot radiotherapy provides effective tumor control in the palliative setting. These findings are comparable with the study conducted by Corry et al., which reported a response rate of approximately 53–77% with the Quad Shot regimen in patients with incurable head and neck cancers8. Another study by Lok et al. also demonstrated encouraging response rates and effective palliation with the RTOG 8502 “Quad Shot” schedule⁹.

Symptom relief is a key objective of palliative treatment. In the present study, significant improvement was observed in symptoms such as pain, dysphagia, bleeding, and foul odor. Pain relief was achieved in more than two-thirds of patients, which contributed significantly to the improvement in daily functioning and patient comfort. Similar results were reported by Paris et al., who observed substantial symptom palliation following hypofractionated radiotherapy regimens in advanced head and neck cancer10.

Quality of life assessment is an essential component in evaluating the effectiveness of palliative therapies. Our study demonstrated significant improvement in global health status, reduction in pain scores, and better swallowing function following Quad Shot radiotherapy. These improvements highlight the importance of short-course radiotherapy schedules in improving the physical and social well-being of patients with advanced disease. Previous studies have also shown that palliative radiotherapy can significantly enhance quality of life by reducing symptom burden and improving functional outcomes8,9.

Regarding treatment tolerance, most patients in the present study experienced mild to moderate acute toxicities (Grade 1–2), and only a small proportion developed Grade 3 mucositis. No Grade 4 toxicity was observed, suggesting that the Quad Shot regimen is safe and well tolerated, even in patients with poor performance status. Similar toxicity profiles have been reported in earlier studies evaluating hypofractionated palliative radiotherapy schedules10.

Overall, the findings of this study support the role of Quad Shot radiotherapy as an effective and practical palliative treatment option in patients with locally advanced or metastatic head and neck cancers. The regimen provides rapid symptom relief, acceptable tumor response, improved quality of life, and minimal treatment-related toxicity, making it particularly suitable for patients who cannot tolerate prolonged radiation schedules.

Quad Shot radiotherapy is an effective palliative treatment modality for patients with locally advanced or metastatic head and neck cancer who are not suitable for curative therapy. The regimen provides good tumor response, significant symptom relief, and improvement in quality of life with minimal toxicity and shorter treatment duration. Therefore, Quad Shot radiotherapy can be considered a valuable and practical option in the palliative management of advanced head and neck cancers, particularly in patients with poor performance status or limited life expectancy.

1.Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide. CA Cancer J Clin. 2018;68(6):394-424.

2.Pignon JP, le Maître A, Maillard E, Bourhis J. Meta-analysis of chemotherapy in head and neck cancer [MACH-NC]. Radiother Oncol. 2009;92(1):4-14.

3.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(2):137-142.

4.Lok BH, Jiang G, Gutiontov S, Lanning RM, Sridhara S, Sherman EJ, et al. Palliative head and neck radiotherapy with the RTOG 8502 regimen for incurable primary or metastatic cancers. Oral Oncol. 2015;51(10):957-962.

5.Murphy BA, Ridner S, Wells N, Dietrich M. Quality of life research in head and neck cancer: A review of the current state of the science. Crit Rev Oncol Hematol. 2007;62(3):251-267.

6.Gupta B, Johnson NW, Kumar N. Global epidemiology of head and neck cancers: A continuing challenge. Oncology. 2016;91(1):13-23.

7.Mehrotra R, Yadav S. Oral squamous cell carcinoma: Etiology, pathogenesis and prognostic value of genomic alterations. Indian J Cancer. 2006;43(2):60-66.

8.Paris KJ, Spanos WJ, Lindberg RD, Jose B, Almagro U. Phase I-II study of accelerated hypofractionated radiotherapy in advanced head and neck cancer. Int J Radiat Oncol Biol Phys. 1993;25(1):65-72.

9.Rogers SN, Lowe D, Fisher SE, Brown JS, Vaughan ED. Health-related quality of life and clinical function after primary surgery for oral cancer. Br J Oral Maxillofac Surg. 2002;40(1):11-18.

10.Agarwal JP, Nemade B, Murthy V, Ghosh-Laskar S, Budrukkar A, Gupta T. Short course palliative radiotherapy in advanced head and neck cancers. Radiother Oncol. 2008;87(1):105-108.