|Year : 2016 | Volume
| Issue : 1 | Page : 138-141
Twice-weekly palliative radiotherapy for locally very advanced head and neck cancers
V Murthy, DP Kumar, A Budrukkar, T Gupta, S Ghosh-Laskar, J Agarwal
Department of Radiation Oncology, ACTREC and Tata Memorial Hospital, Tata Memorial Centre, Mumbai, Maharashtra, India
|Date of Web Publication||28-Apr-2016|
Department of Radiation Oncology, ACTREC and Tata Memorial Hospital, Tata Memorial Centre, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Purpose: The purpose of the following study is to evaluate the efficacy of a twice-weekly hypofractionated palliative radiotherapy schedule in locally very advanced head and neck cancers. Materials and Methods: Patients with locally very advanced, head and neck cancers were prospectively evaluated after twice-weekly palliative radiotherapy regimen of 32 Gy in 8 fractions. Median age was 55.5 years and the predominant primary site was oral cavity (46%). Majority (70.6%) had Stage IV B disease. Disease related distressing symptoms such as pain, bleeding, skin fungation, respiratory symptoms due to tumor burden, were prospectively assessed before the start of treatment, at conclusion and at 6-12 weeks of completion of treatment. Results: A total of 126 patients were enrolled in the study. Ninety three (73.8%) patients who completed the planned treatment of 32 Gy in 8 fractions were included in the symptom analysis. Overall response rates were 42% at primary disease and 55% at nodal disease. At conclusion of radiotherapy 76.3% of the patients reported improvement in pain scores (P = 0.001) and 42.8% patients reported improvement in anxiety and depression levels (P = 0.001). At first follow-up after 6-12 weeks significant improvement in pain scores (P = 0.001) and anxiety/depression levels (P = 0.001) persisted. The median survival of the patients was 5.5 months. Acute grade III mucositis was seen in one patient (1.2%) while none had grade III skin reactions. Conclusion: The proposed radiotherapy regimen is effective for sustained symptom palliation with low acute toxicity in locally very advanced head and neck cancers. It delivers a moderately high dose while being logistically simpler for the patient.
Keywords: Head and neck cancers, locally very advanced, palliative radiotherapy
|How to cite this article:|
Murthy V, Kumar D P, Budrukkar A, Gupta T, Ghosh-Laskar S, Agarwal J. Twice-weekly palliative radiotherapy for locally very advanced head and neck cancers. Indian J Cancer 2016;53:138-41
|How to cite this URL:|
Murthy V, Kumar D P, Budrukkar A, Gupta T, Ghosh-Laskar S, Agarwal J. Twice-weekly palliative radiotherapy for locally very advanced head and neck cancers. Indian J Cancer [serial online] 2016 [cited 2019 Sep 15];53:138-41. Available from: http://www.indianjcancer.com/text.asp?2016/53/1/138/180847
| » Introduction|| |
A vast majority of Head and Neck Squamous cell cancers (HNSCC) in India present in advance stages  and are not candidates for multimodality treatment due to loco-regionally very advanced disease, poor performance status or distant metastatic disease. Traditionally, hypofractionated regimens have been used for palliation of locally very advanced head and neck cancers due to radiobiological advantages (large dose per fraction), shorter overall treatment time and logistical convenience and limited life expectancy in this group of patients. The increased potential for late side effects with hypofractionated radiotherapy  is less relevant due to limited life expectancy in this group of patients. Due to lack of consensus guidelines unlike radical radiotherapy, on the optimal fractionation schedule, a number of different hypofractionated regimens have been used across the globe for treatment of locally advanced head and neck cancers.,, To palliate large disease volumes in locally very advanced HNSCC, there is need to balance a moderately high radiation doses while keeping the overall treatment time and number of hospital visits small. This work is an analysis of patients of locally very advanced head and neck cancer treated at our institute with short course hypofractionated radiotherapy regimen of 32 Gy in 8 twice weekly (Wednesday/Saturday), fractions. The regimen was designed to deliver a reasonable tumoricidal dose in short duration of time and with fewer hospital visits. All patients in this cohort had a poor prognosis at presentation owing to large disease burden, poor performance status, coexisting co-morbidities and/or advanced age. The purpose of the present work was to determine the feasibility and efficacy of the proposed radiotherapy protocol in this cohort of locally very advanced head and neck cancers.
| » Materials and Methods|| |
Between 2008 and 2011, 126 patients of locally advanced HNSCC considered unsuitable for definitive treatment were selected for analysis. These included patients with histologically confirmed cancer with stage IVB disease (surgically unresectable), patients with poor performance status without history of previous radiotherapy or chemotherapy. All the patients after complete staging work-up were discussed in the multidisciplinary joint clinic and were found unsuitable for curative treatment due to extensive loco-regional disease, poor performance status and/or the presence of distant metastatic disease. Staging work up for each patient included a thorough physical examination with indirect/direct laryngoscopy, cross-sectional imaging of face and neck and a chest X-ray. All data was planned and collected prospectively.
The primary end point was subjective improvement in distressing symptoms such as pain, dysphagia, bleeding, skin fungation, pressure related respiratory symptoms, anxiety and associated depression. Secondary end point was to evaluate response rates, toxicity and survival. Patients were asked to report pain levels on a score of 1-10 depending upon the severity of pain. Other parameters were patient reported and recorded in a graded manner assisted by a trained health care professional before treatment, at conclusion of radiotherapy and at first follow-up after 6-12 weeks. Long-term assessment was not planned as most patients were not likely to follow-up at the hospital due to logistic, geographical and health related reasons.
Treatment was planned on a conventional simulator with immobilization in a thermoplastic mask. Wires were used to delineate any palpable nodal disease. The treatment volume included the symptomatic gross disease (primary tumor and/or nodal disease). The radiation field encompassed the gross disease with a 1.5-2.0 cm margin. Treatment techniques and portals varied depending upon the location and the extent of the disease. Elective nodal irradiation was not done in order to reduce the treatment volumes and related toxicities.
All patients were planned to be treated with palliative hypo-fractionated radiotherapy to dose of 32 Gy in 8 fractions, given twice weekly (Wednesday and Saturday). Patients with good objective regression and symptomatic relief as assessed by the treating physician were given an additional dose of 20 Gy in 5 fractions. In the second phase of treatment if required, patients were treated with “off cord” portals, with an electron field to the posterior neck if clinically indicated. All patients were reviewed at least once weekly during the treatment course for assessing toxicity. The radiation therapy oncology group (RTOG) grading was used to document toxicity. Symptom relief for the purpose of analysis was assessed at the conclusion of radiotherapy and at first follow up after 6-12 weeks. The modified World Health Organization criteria were used to assess tumor response to radiotherapy, which was documented at conclusion of radiotherapy and 6-8 weeks after the completion of treatment as follows. Complete response was defined as complete regression of primary or nodal disease, good response as more than 75% reduction in the size of primary or nodal disease, moderate regression as 50-75% regression in size, poor response as <50% regression in size of primary, stable disease as <25% regression in size of primary. Progressive disease was defined as any increase in the size of disease or appearance of a new lesion in the field.
Descriptive statistics were used to estimate the patient demographics, disease and treatment parameters and toxicity after therapy. Impact of radiotherapy on symptoms with paired ordinal data was analyzed using Wilcoxon Signed rank test while Mc Nemar test was used for binary variables. The Kaplan–Meier method was used to estimate median overall survival (OAS), progression free survival (PFS). OAS was measured from commencement of radiotherapy until the date of death from any cause. The PFS was measured from commencement of radiotherapy until the date of first progression or death. Multiple-covariate analysis of prognostic factors was done by Cox regression backward-conditioning method.
| » Results|| |
A total of 126 patients were enrolled in the study. Their demographic profile is shown in [Table 1]. Majority of the patients were male (82.5%) and the median age was 55.5 (25-85) years. The predominant primary site was oral cavity (46%) and 70.6% had stage IVB disease. Of the 126 patients, 33 patients did not complete the planned course of radiotherapy. They defaulted at various stages of treatment and while their baseline data was available, but they were not available for assessment of subjective and objective response. The median dose for these patients was 24 Gy with a range of 12-28 Gy. Twenty four24 (25.8%) patients with good subjective regression or symptomatic relief received additional dose of 20 Gy in 4 fractions. Ninety three patients who completed the prescribed course of radiotherapy were analyzed for response and symptom assessment at radiotherapy conclusion. At first follow-up, 46 patients were available for assessment of response and symptoms.
Following treatment, the median pain score improved significantly from 7 to 4 at conclusion and 3 at first follow-up. Bleeding and fungation rates improved from 8.5% and 11.7% to 5.3% and 9.7% respectively after completion of treatment. There was a statistically significant improvement in anxiety and depression in patients from 95% pre-treatment levels to 53% at the conclusion of planned treatment [Table 2].
[Table 3] shows the response rates after radiotherapy. Overall response in the primary site was 42% and at the nodal site was 55%.
At the time of analysis 69 patients (74%) have died. The median survival of the patients was 5.5 months. On univariate analysis patients with stage IVA, Karnofsky Performance Status >80 and good response to radiation therapy had statistically significant superior OAS. On multivariate analysis, stage of the disease was found to be the only significant predictor of OAS (P = 0.045).
Treatment related toxicity
After completion of planned treatment, 46% had RTOG grade I dysphagia, compared with 42% at baseline. Fifty percent patients developed grade II mucositis, and only one patient developed grade III mucositis. None of the patients developed grade III skin toxicity while 45% patients developed grade II skin toxicity. None of the patients required tracheostomy or assisted feeding during the course of radiotherapy although few patients had feeding tube prior to radiotherapy treatment.
| » Discussion|| |
In the present study, patients with locally very advanced head and neck cancers were treated with twice weekly palliative radiotherapy 32 Gy in 8 fractions with 25% of the patients receiving an additional 20 Gy in 5 fractions. There was significant improvement in the pain and anxiety/depression levels after palliative radiotherapy.
Locally very advanced HNSCC differ from the well-defined group of locally advanced head and neck cancers, in the extent of the disease. These are cases with either, a very large volume, inoperable primary disease (T4b disease) or a large fixed or fungating nodal mass making them ineligible for curative treatment. In the absence of any treatment the median survival of patients with such loco-regionally very advanced HNSCC is 100 days. However this group of patients still merit some treatment to alleviate disease related distressing symptoms and to control loco-regional disease.
A number of palliative radiotherapy regimens are in use worldwide, without robust data on the best approach.,, Palliative benefits of hypofractionated and conventional fractionated radiotherapy were found to be comparable, with no difference in acute or late toxicity in a small randomized control trial comparing conventional radiotherapy (60-70 Gy/30-35 fractions) with short-course hypofractionated radiotherapy (40-48 Gy/10-12 fraction, 4 fractions per week). The hypofractionated regimen of 32 Gy/8 fractions used in the current study was designed to deliver a reasonably high tumoricidal dose (Biological Equivalent Dose [BED] of 45 Gy for tumor control and 74 Gy for late effects) to achieve sustained local control and symptom relief. Patients with good response received a higher dose of 52 Gy/13 fractions which amounts to BED of 72.8 Gy. Fewer fractions allowed treatment completion before accelerated repopulation. Furthermore as a number of patients were coming from faraway places within the city, fewer hospital visits were often welcomed by the patient.
In spite of developing some amount of radiotherapy induced mucosal reactions, after completion of palliative radiotherapy 83% of patients reported improvement in pain scores. The median pain score improved from 7 at presentation to 4 at conclusion of radiotherapy (P = 0.0001). At first follow-up after 3 months median pain scores reduced further to 3 (P = 0.007). The “Hypo trial” which included patients with incurable HNSCC treated with hypofractionated radiotherapy of 30 Gy in 5 fractions at 2 fractions/week, reported 67% improvement in pain and the QUAD SHOT study reported 56% (15/27) improvement in pain scores in., In a trial reported from North India, Mohanti et al. reported symptom relief for pain, dysphagia, hoarseness, cough and otalgia in 47-59% of the patients following palliative radiotherapy using 20 Gy/5 fractions, with 30% of the patients receiving additional dose of 42 Gy in 21 fractions. Das et al. have reported significant pain relief (more than 50%) in about 88% of patients and worsening in 9% patients at the end of radiotherapy.
Palliative radiotherapy also helped in relieving the anxiety and depression from 95% at presentation to 55% (P = 0.0001) at completion of radiotherapy. This trend was maintained at follow-up. This could also be direct effect of the patient receiving treatment and hoping that they will get better, in spite of being counseled otherwise. This aspect of patient care has not been studied in any of the previous studies of palliative radiotherapy in head and neck cancers. Improvement in ulceration, skin fungation, bleeding and respiratory distress levels after palliative radiotherapy were not statistically significant due to small number of patients having these symptoms at presentation.
Response rates after palliative radiotherapy have not been uniform. Minatel et al. in their study have reported local tumor response rates of 69% with a split course radiotherapy, 50 Gy in 20 fractions, and bleomycin in a group of patients with inoperable head and neck cancer. The overall objective (CR + PR) response rates were 80% and 53% in the QUAD SHOT and Hypo trial respectively., Agrawal et al. have reported CR in 10% and PR in 63% of the patients using hypofractionated regimen of 40 Gy in 16 fractions. In the present study, the overall response rates were 42% at primary disease and 55% at nodal disease. The lower response rates can be partly explained by larger disease burden, with 70% of the patients having stage IVB disease, whereas in the Hypo trial only 73% patients had stage III/IV disease and in the QUAD SHOT trial all patients had either stage III/IV disease.,
An important aim of any palliative regimen is to offer symptom relief with a minimal treatment related toxicity. The treatment in this study was tolerated well and the treatment related acute toxicities were lower than most of the studies of palliative radiotherapy in head and neck cancers. In the present study, 50% patients developed grade II mucositis and only 1 (1.2%) patient developed grade III mucositis. None of the patients developed grade III skin toxicity while 45% patients developed grade II skin toxicity. The rate of grade III mucositis was 26% in the Hypo trial and 47% in the Italian study., Mohanti et al. reported 62% grade III mucositis and 56% grade III dermatitis in their study. Agarwal et al. reported 63% grade III mucositis and 14% grade III dermatitis in their study using a BED of 50 Gy for acute effects. Incidence of grade III mucositis and dermatitis and pain was 18%, 3%, in a study by Das et al. The possible explanation for lower acute toxicity lies in the lower weekly accumulated dose of 8 Gy and time gap between two fractions resulting in a reduction in acute normal tissue reactions.
Due to short median follow-up it is not possible to draw any conclusion related to late toxicities in the current study. Furthermore due to short expected median survival in this group of patients, the late toxicities are not a major concern in this patient subgroup.
In this study, only 74% of the patients could complete the planned treatment. Of the 27 patients who could not complete the planned treatment 16 patients (59%) died during the course of treatment while remaining 11 (41%) defaulted due to various reasons. The higher death (13%) and drop out (9%) rate before the completion of treatment rate calls for a very careful selection of patients for palliative radiotherapy in this group of locally very advanced head and neck cancers.
The limitations of the present study are that, it is not randomized, although the data was prospectively collected and analyzed. There was a significant attrition of patients post radiotherapy conclusion despite active and continuous attempts to contact patients for follow up. This was due to the fact that many patients were from outstation. There is lack of documentation of analgesic usage both during and after radiotherapy.
| » Conclusion|| |
The studied palliative radiotherapy regimen has promise to deliver reasonably high dose to achieve significant pain relief with minimal acute toxicity in patients with locally very advanced head and neck cancers. Comparison with other dose fractionation regimen and palliative chemotherapy is warranted.
| » References|| |
Kumar S. National palliative care policy for India. Indian J Palliat Care 2000;6:62.
Steel GG. Basic clinical radiobiology. 3rd
ed. New York: Hodder Arnold; 2002.
Radiotherapy Dose Fractionation. London: Royal College of Radiologists; Board of Faculty of Clinical Oncology, Royal College of Radiology; 2006;pp. 40-3.
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.
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.
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.
Kowalski LP, Carvalho AL. Natural history of untreated head and neck cancer. Eur J Cancer 2000;36:1032-7.
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.
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.
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.
Minatel E, Gigante M, Franchin G, Gobitti C, Mascarin M, Bujor L, et al
. Combined radiotherapy and bleomycin in patients with inoperable head and neck cancer with unfavourable prognostic factors and severe symptoms. Oral Oncol 1998;34:119-22.
Hopewell JW, Nyman J, Turesson I. Time factor for acute tissue reactions following fractionated irradiation: A balance between repopulation and enhanced radiosensitivity. Int J Radiat Biol 2003;79:513-24.
[Table 1], [Table 2], [Table 3]
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