|Year : 2017 | Volume
| Issue : 3 | Page : 493-497
Radical radiotherapy for carcinoma of the larynx in the elderly: Functional and oncological outcomes from a tertiary cancer care center in India
Narayana R Subramaniam1, Vijay Kumar Srinivasalu2, Deepak Balasubramanian1, KU Pushpaja3, Anoop Remesan Nair3, Chelakkot Prameela1, Krishnakumar Thankappan1, Subramania Iyer1
1 Department of Head and Neck Oncology, Amrita Institute of Medical Sciences, Amrita University, Kochi, Kerala, India
2 Department of Medical Oncology, Amrita Institute of Medical Sciences, Amrita University, Kochi, Kerala, India
3 Department of Radiation Oncology, Amrita Institute of Medical Sciences, Amrita University, Kochi, Kerala, India
|Date of Web Publication||24-May-2018|
Dr. Deepak Balasubramanian
Department of Head and Neck Oncology, Amrita Institute of Medical Sciences, Amrita University, Kochi, Kerala
Source of Support: None, Conflict of Interest: None
INTRODUCTION: It is estimated that around 10% of all head and neck cancer patients in India are aged over 70 years. Elderly patients are often subjected to palliative or inadequate treatment for head and neck cancers in spite of being candidates for curative intent therapy. In this study we evaluated our use of radical radiotherapy in carcinoma larynx for patients over seventy years of age to determine morbidity, likelihood of completing therapy, functional and oncological outcomes. MATERIALS AND METHODS: 132 patients of squamous cell carcinoma of the larynx treated between 2005-2015 at Amrita Institute of Medical Sciences, Kochi who were seventy years of age or older were included. The endpoint for analysis was overall survival. Survival curves were generated using Kaplan Meier method and univariable analysis was performed using log rank test. RESULTS: The median age of patients was 77 years (range 70-102). All patients (100%) completed radiotherapy with 6 (5%) requiring treatment breaks. All patients had at least minor (grade I/II) toxicities. Grade III toxicities were seen in 10 (8%) of patients. No grade IV reactions or treatment related deaths occurred. When a univariate analysis was performed for determinants of major toxicities with age range, performance status, smoking, number of co-morbidities or TNM stage, no determinants were statistically significant. 2-year disease free survival for stage I, II, III and IV was 100%, 98%, 80% and 64% respectively, and the 2-year overall survival for all four stages was 100%. CONCLUSION: Patients over seventy years tolerate radical radiotherapy for treatment of laryngeal cancer. In spite of minor toxicities, all patients completed treatment and had good oncological outcomes. Patients with stage III/IV unfit for concomitant chemotherapy administration treated with radiotherapy alone had a good disease free survival. Curative intent therapy should not be withheld from elderly patients on the basis of age.
Keywords: Elderly, laryngeal cancer, radiotherapy, squamous cell carcinoma
|How to cite this article:|
Subramaniam NR, Srinivasalu VK, Balasubramanian D, Pushpaja K U, Nair AR, Prameela C, Thankappan K, Iyer S. Radical radiotherapy for carcinoma of the larynx in the elderly: Functional and oncological outcomes from a tertiary cancer care center in India. Indian J Cancer 2017;54:493-7
|How to cite this URL:|
Subramaniam NR, Srinivasalu VK, Balasubramanian D, Pushpaja K U, Nair AR, Prameela C, Thankappan K, Iyer S. Radical radiotherapy for carcinoma of the larynx in the elderly: Functional and oncological outcomes from a tertiary cancer care center in India. Indian J Cancer [serial online] 2017 [cited 2018 Dec 14];54:493-7. Available from: http://www.indianjcancer.com/text.asp?2017/54/3/493/233147
| » Introduction|| |
Head and neck cancers account for a major percentage of the cancer burden in India, and it is estimated that around 10% of patients are aged over 70 years. In the context of an aging population with a longer life expectancy, this percentage is expected to expand rapidly in the coming decades. In the context of a higher incidence of comorbid illness and reduced performance status, elderly patients are often subjected to palliative or inadequate treatment for head and neck cancers in spite of being candidates for curative intent therapy.
The definition of elderly is variable, with 70 years of age being considered a landmark due to the alteration in physiological status and treatment-related toxicity in cancer. Other definitions have included 65, 75, or 85 years of age. Equally important to remember is the concept of “physiological age,” where depending on the performance status and presence of comorbid illness, the toxicity profile of patients may resemble either patients of an older or younger age group.
Western literature has shown the use of radical radiotherapy for head and neck cancers in the elderly to be effective and safe;, however, data from India are scanty. The reasons why specific data are relevant are several. Compared to patients in the West, Indian patients have been shown to have a low compliance to cancer therapy, a significantly lower life expectancy of around 68 years  and much more likely to incur out-of-pocket expenditure for cancer therapy due to the lack of universal healthcare, which may significantly impact treatment decisions.
Our institutional policy has always been to offer curative intent treatment to all patients with a good performance status irrespective of age. In this study, we evaluated our use of radical radiotherapy in patients of carcinoma of the larynx over 70 years of age to determine their pattern of morbidity, likelihood of completing therapy, and functional and oncological outcomes.
| » Materials and Methods|| |
From a prospectively maintained database of patients treated at Amrita Institute of Medical Sciences, Kochi, Kerala, India, we identified 132 patients of squamous cell carcinoma of the larynx treated between 2005 and 2015 who were 70 years of age or older. The management for all cases was discussed in the multidisciplinary tumor board, and those who were recommended for curative intent radiotherapy and were treated in our institution were included. Pretreatment evaluation in all patients was with clinical evaluation, cross-sectional imaging (contrast-enhanced computerized tomography, magnetic resonance imaging, or positron emission tomography [PET] scans), and biopsies from the tumor.
Radiotherapy was delivered by 3D conformal radiotherapy (3DCRT). Planning was by computed tomography (CT) simulation from vertex to mid-thorax (level of T6 vertebra) with 3 mm slice thickness. Contouring was as per RTOG guidelines  with contouring of the gross tumor volume (GTV) and the clinical target volume, which was the GTV plus areas at risk for microscopic disease spread. The dose and fractionation varied between the subsite of disease and stage as shown in [Table 1]. Radiotherapy was delivered using linear accelerators, and treatment was administered on 5 days a week.
Response to therapy was assessed by clinical/endoscopic assessment for all patients and imaging (CT or PET) after completing 12 weeks of treatment in cases of suspected residual/recurrent disease. Clinical visits were advised as monthly for the first 12 months, alternate monthly for the next 12 months, once in 3 months for the 3rd year, once in 4 months for the 4th year, and 6 monthly for the 5th year. In addition to assessment for disease status, patients were assessed for toxicities related to treatment and advised treatment/rehabilitation for these wherever feasible.
Recurrent disease was defined as any proven local, regional, or distant disease occurring at least 3 months after date of completing radiotherapy. Overall survival (OS) was defined as time from date of starting radiotherapy to date of death or last follow-up evaluation.
Statistical analysis was performed using SPSS version 20 (IBM, New York, USA). The endpoint for analysis was OS. Survival curves were generated using the Kaplan–Meier method and univariable analysis was performed using the log-rank test. All statistics were two-sided, and P < 0.05 was considered statistically significant.
| » Results|| |
Patient and disease characteristics
One hundred and thirty-two patients were included in our study [Table 1]. The median age of patients was 77 years (range 70–102), with males comprising 95% of patients. One hundred and twenty patients (91%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 1, while the remaining 12 (9%) had a performance status of 2. Sixty-six patients (50%) were smokers. The subsite involved was supraglottis in 22 (17%), glottis in 103 (78%), and subglottis in 7 (5%) patients. Sixty-four patients (48%) had no comorbidities while the remaining had one or more. Stage of the disease was I, II, III, and IV in 75 patients (56%), 34 patients (26%), 18 patients (14%), and 5 patients (4%), respectively. Although Stage III/IV disease typically receives multimodal treatment, namely, chemoradiotherapy, these patients received radiotherapy alone as their age or functional status precluded the use of concurrent chemotherapy. Follow-up was for a median of 25 months (range 2–120 months).
As shown in [Figure 1], all patients completed radiotherapy, of which six patients (5%) required treatment breaks. The mean treatment break was 7 days (range 2–12 days). The dose of radiation and fractionation was variable depending on the site and stage of disease.
|Figure 1: Overall survival in months based on tumor, node, and metastasis stage. Two-year overall survival for all stages was 100%|
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All patients had at least minor (Grade I/II) toxicities, which were self-limiting [Table 2]. The most common toxicities were mucositis, skin reactions, or dysphagia. Grade III toxicities were seen in 10 (8%) of patients. No Grade IV reactions were noted. There were no treatment-related deaths. When a univariate analysis was performed for determinants of major toxicities [Table 3] and [Figure 2], no determinants were statistically significant; however, patients with a worse performance status and advanced Stage (III/IV) were at a higher risk of Grade III toxicity (relative risk 3.05 and 2.14, respectively). Patients over 80 years were also more likely to develop Grade III toxicity (relative risk 2.2).
|Figure 2: Disease-free survival in months based on patient age. Key: 70: Age >70 years, 80: Age >80 years, 90: Age >90 years|
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Response to therapy
All patients had a complete resolution of disease following treatment (100%). This was determined by clinical evaluation and imaging wherever applicable. Of the remaining patients, 14 (11%) had recurrences, of which 10 (71%) were locoregional and 4 (29%) were metastatic.
Disease-free survival (DFS) and OS were determined using Kaplan–Meier method. We compared the DFS based on tumor, node, and metastasis (TNM) stage and the 2-year DFS for Stages I, II, III, and IV was 100%, 98%, 80%, and 64%, respectively [Figure 3]. The 2-year OS for all four stages was 100% [Figure 1]. When we determined DFS based on age at diagnosis, the 2-year DFS for those 70–80 years, 80–90 years, and >90 years were equal at 92% [Figure 2].
|Figure 3: Disease-free survival in months based on tumor, node, and metastasis stage. Two-year disease-free survival for Stages I, II, III, and IV was 100%, 98%, 80%, and 64%, respectively|
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| » Discussion|| |
Our study demonstrated that radical radiotherapy is an effective therapeutic modality for use in patients over 70 years of age, even with 3DCRT. All 132 patients completed radiotherapy with only 5% of them requiring treatment breaks. Minor toxicity occurred in all patients; however, major morbidity occurred in only 8% of patients. Although intensity-modulated radiotherapy is shown to be associated with less morbidity, it is not available in all areas and is more expensive than 3DCRT; our data show that elderly patients are likely to tolerate radical 3DCRT.
Ideally, radical radiotherapy as a lone modality should be used in Stage I/II patients; however, our study included 23 patients (18%) of Stage III/IV disease. The reason why these patients did not receive concurrent chemotherapy was because of poor performance status or advanced age, and the resulting low likelihood of survival benefit from its addition. Interestingly, even in Stage III/IV elderly patients, radical radiotherapy offered a good locoregional control rate (LCR), with 2-year DFS of 80% and 62%, respectively. Expectedly, beyond 2 years, the LCR reduced and the recurrences occurred, with a resultant fall in OS.
We determined the DFS as a function of age, to determine if there was any variation in LCR based on age at diagnosis [Figure 2]. All age groups had a good DFS for the first 2 years; there was no impact of age at diagnosis on DFS. Even patients aged above 90 years benefited from curative intent radiotherapy; all patients were disease-free at 2 years, implying that even when concurrent chemotherapy is not a reasonable therapeutic option, radical radiotherapy resulted in good disease control for at least 2 years.
Although limited data exist on the use of radical radiotherapy in elderly Indian patients,, it has shown that it is a reliable and safe therapeutic modality. Studies with much larger numbers from western literature have shown that elderly patients have a similar survival and toxicity profile as their younger counterparts when treated with radical radiotherapy.,, The study by Pignon et al. was a secondary analysis of four trials conducted by the European Organization for Research and Treatment of Cancer (EORTC); it showed no difference in OS when comparing patients of four distinct subgroups, even those >75 years, and that accelerated concomitant boost radiation was safe in the elderly. The incidence of Grade III–IV toxicity was higher in the elderly; however, when adjusted for performance status, age was not found to be an independent predictor of toxicity or treatment discontinuation. When age was studied as a continuous variable, there was a significant reduction in cause-specific survival, which was very modest (relative risk of 1.03).
It is vital to remember that trial patients are often extremely fit and conform to a selection bias; elderly patients from the EORTC trials were likely to represent those with the best functional status and most likely to complete therapy. This is reflected in other retrospective studies, where the completion rate for radiotherapy was lower. Lusinchi et al. showed a failure to complete radiotherapy in 9% of his cohort of over 300 patients. Treatment breaks were also more common in the elderly when compared to the young as shown in several studies.,, Our results were similar, with 5% requiring treatment breaks, but all patients were able to complete treatment. These treatment breaks were also not seen to impact treatment. The factors that were associated with a higher risk of major toxicity in our study were age over 80 years (relative risk 2.2), ECOG performance status of 2 (relative risk 3.05), and advanced TNM stage (relative risk 2.14). Advanced stage of disease (III/IV) is expected to increase the risk of major toxicity due to the higher volume of disease and consequently treatment volumes and dose of radiotherapy administered. Advanced age (over 80 years) and poorer performance status are likely to represent poorer general condition, wound healing, and regenerative capacity.
An important factor to note in our studies as well as others is that elderly patients with an ECOG performance status of 2 or higher were not included. Many of these patients received palliative radiotherapy at significant lower doses. Patients with a poor performance status are far less likely to have the physiological reserve to withstand major toxicity and complete treatment; this is a factor to be kept in mind during treatment planning. Patients who are unlikely to withstand the full course of radical therapy would be better served with a palliative dose of radiotherapy in fewer fractions.
Another important consideration is supportive care. As per our institutional policy, all of our elderly patients received geriatric care, palliative care, and swallowing rehabilitation throughout the treatment period. Elderly patients have been shown to be at higher risk of certain late toxicities of treatment  and are likely to require more extensive nutritional and rehabilitative support. Periodic assessment is mandatory; certain toxicities such as aspiration following administration of radiotherapy to the dysphagia and aspiration-related structures could be life-threatening to those in the elderly age group with poor pulmonary and physiological reserve.
| » Conclusion|| |
Patients over 70 years having a good performance status who receive radical radiotherapy for head and neck squamous cell carcinoma of the larynx are likely to complete therapy with an acceptable incidence of major and minor toxicities. Aggressive rehabilitation and supportive care are vital to enable early identification of toxicities and appropriate treatment. Patients of Stage III/IV disease who are unlikely to tolerate chemotherapy may also achieve a good 2-year LCR with radical radiotherapy alone. Even patients over 90 years are likely to benefit from radical radiotherapy for disease control; advanced age without consideration of functional status should not be the sole determinant of therapeutic intent.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]